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Propane dehydrogenation (PDH) is a highly efficient approach for industrial production of propylene, and the dual-atom catalysts (DACs) provide new pathways in advancing atomic catalysis for PDH with dual active sites. In this work, we have developed an efficient strategy to identify promising DACs for PDH reaction by combining high-throughput density functional theory (DFT) calculations and the machine-learning (ML) technique. By choosing the γ-Al2O3(100) surface as the substrate to anchor dual metal atoms, 435 kinds of DACs have been considered to evaluate their PDH catalytic activity. Four ML algorithms are employed to predict the PDH activity and determine the relationship between the intrinsic characteristics of DACs and the catalytic activity. The promising catalysts of CuFe, CuCo and CoZn DACs are finally screened out, which are further validated by the whole kinetic reaction calculations, and the highly efficient performance of DACs is attributed to the synergistic effects and interactions between the paired active sites.
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Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (Pâ <â .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (Pâ <â .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months Pâ <â .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.
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Estatura , Enanismo , Hormona de Crecimiento Humana , Proteínas Recombinantes , Humanos , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/economía , Niño , Estudios Retrospectivos , Masculino , Femenino , Enanismo/tratamiento farmacológico , Enanismo/economía , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/economía , Proteínas Recombinantes/administración & dosificación , Estatura/efectos de los fármacos , Resultado del Tratamiento , Preescolar , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/economía , Trastornos del Crecimiento/etiología , Economía Farmacéutica , Análisis Costo-Beneficio , Costos de la Atención en Salud/estadística & datos numéricos , AdolescenteRESUMEN
BACKGROUND: The most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target for TNBC. METHODS: The mRNA expression levels of NUDT5 in breast cancers were investigated using TCGA and METABRIC (Curtis) datasets. NUDT5 ablation was achieved through siRNA targeting and NUDT5 inhibition with the small molecule inhibitor TH5427. Xenograft TNBC animal models were employed to assess the effect of NUDT5 inhibition on in vivo tumor growth. Proliferation, death, and DNA replication assays were conducted to investigate the cellular biological effects of NUDT5 loss or inhibition. The accumulation of 8-oxo-guanine (8-oxoG) and the induction of γH2AX after NUDT5 loss was determined by immunofluorescence staining. The impact of NUDT5 loss on replication fork was assessed by measuring DNA fiber length. RESULTS: In this study, we demonstrated the significant role of an overexpressed phosphatase, NUDT5, in regulating oxidative DNA damage in TNBCs. Our findings indicate that loss of NUDT5 results in suppressed growth of TNBC both in vitro and in vivo. This growth inhibition is not attributed to cell death, but rather to the suppression of proliferation. The loss or inhibition of NUDT5 led to an increase in the oxidative DNA lesion 8-oxoG, and triggered the DNA damage response in the nucleus. The interference with DNA replication ultimately inhibited proliferation. CONCLUSIONS: NUDT5 plays a crucial role in preventing oxidative DNA damage in TNBC cells. The loss or inhibition of NUDT5 significantly suppresses the growth of TNBCs. These biological and mechanistic studies provide the groundwork for future research and the potential development of NUDT5 inhibitors as a promising therapeutic approach for TNBC patients.
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Pirofosfatasas , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Línea Celular Tumoral , Proliferación Celular , Pirofosfatasas/genética , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Five new steroidal saponins, paripolins D-H (1-5), and 6 known compounds (6-11) were isolated from the aerial parts of Paris polyphylla var. yunnanensis. The structures of 1-5 were determined using spectroscopic analyses in conjunction with acid hydrolysis. It is for the first time to report the 12-hydroxysteroidal saponins from the genus Paris. The effect of all isolated compounds on blood coagulation was determined in vitro using the plasma recalcification time method. Compounds 1 and 2 showed potent procoagulant activity, and 5-11 exhibited significant anticoagulant activity.
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Liliaceae , Saponinas , Liliaceae/química , Rizoma/química , Estructura Molecular , Saponinas/farmacología , Saponinas/química , Coagulación SanguíneaRESUMEN
There has been increasing interests in π-d conjugated coordination polymers (CCPs) for energy storage because of their rapid charge transfer through long-range planar π-d conjugation between ligands and metal centers. Nevertheless, currently reported CCPs for energy storage are mostly based on 1D or 2D structures. There are few 3D CCPs reported to date because of the great challenge in constructing nonplanar coordination geometries, let alone their applications in multivalent ions storage. Herein, a triphenylene-catecholate-based 3D CCP (Mn-HHTP) is successfully synthesized assembled from the multidentate chelating groups of hexahydroxytriphenylene (HHTP) ligands and their isotropic coordination with Mn2+ ions. The 3D conjugated structure of Mn-HHTP enables an exceptional cycle life of >4000 cycles at 0.5 A g-1 for multivalent Mg2+ ion storage, which is far superior to most organic and inorganic electrode materials. Experimental characterizations combined with theoretical calculations indicate that the semiquinone radicals at the HHTP ligands are the electroactive centers for Mg2+ ions storage. The excellent performance of Mn-HHTP opens a new avenue towards the design of 3D CCPs for long-life rechargeable magnesium-ion batteries.
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Background: Intestinal pathogens are associated with xenotransplantation tolerance and rejection. However, changes in the gut microbiota in patients who have undergone peripheral nerve xenotransplantation and their association with immune rejection have not yet been reported. Objective: We aimed to explore intestinal microbes and their metabolites at different time points after peripheral nerve transplantation to provide new insight into improving transplant tolerance. Methods: A peripheral nerve xenotransplantation model was constructed by suturing the segmented nerves of Sprague Dawley rats to those of C57 male mice using xenotransplantation nerve bridging. Fecal samples and intestinal contents were collected at three time points: before surgery (Pre group; n = 10), 1 month after transplantation (Pos1 m group; n = 10), and 3 months after transplantation (Pos3 m group; n = 10) for 16S DNA sequencing and nontargeted metabolome detection. Results: Alpha diversity results suggested that species diversity was significantly downregulated after peripheral nerve xenotransplantation. There were six gut flora genera with significantly different expression levels after xenotransplantation: four were downregulated and two were upregulated. A comparison of the Pre vs. Pos1 m groups and the Pos1 m vs. Pos3 m groups revealed that the most significant differentially expressed Kyoto Encyclopedia of Genes and Genomes metabolite pathways were involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine metabolism. Metabolites with a strong relationship to the differentially expressed microbial flora were identified. Conclusion: Our study found lower gut microbiome diversity, with increased short-chain fatty acid (SCFA)-producing and sulfate-reducing bacteria at 1 month post peripheral nerve xenotransplantation, and these were decreased at 3 months post-transplantation. The identification of specific bacterial metabolites is essential for recognizing potential diagnostic markers of xenotransplantation rejection or characterizing therapeutic targets to prevent post-transplant infection.
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A series of model tests were conducted to investigate the bearing capacity and reinforced mechanism of a horizontal-vertical (H-V) geogrid-reinforced foundation. The bearing capacities of the unreinforced foundation, the conventional geogrid, and the H-V geogrid-reinforced foundation were compared. The parameters, including the length of the H-V geogrid, the vertical geogrid height, the depth of the top layer, and the number of H-V geogrid layers, are discussed. Through experiments, it was found that the optimal length of H-V geogrid is around 4B, the optimal vertical geogrid height is approximately 0.6B, and the optimal depth of the top H-V geogrid layer is between 0.33B and 1B. The optimal number of H-V geogrid layers is 2. The result also indicates that the bearing capacity of H-V geogrid is almost 1.7 times greater than that of conventional geogrid. Additionally, the maximum top subsidence of H-V geogrid-reinforced foundation decreased by 13.63% compared to that of conventional geogrid-reinforced foundation. Under the same settlement, the bearing capacity ratio of two H-V geogrid-reinforced foundation layers is 75.28% higher than that of one layer. The results also demonstrate that the vertical elements of H-V geogrid interlock the sand from being displaced under the applied load and redistribute the surcharge over a wider area, thereby increasing the shear strength and improving the bearing capacity of an H-V geogrid-reinforced foundation.
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Bone defects that result from trauma, infection, surgery, or congenital malformation can severely affect the quality of life. To address this clinical problem, a phosphoserine-loaded chitosan membrane that consists of chitosan membranes serving as the scaffold support to accommodate endogenous stem cells and phosphoserine is synthesized. The introduction of phosphoserine greatly improves the osteogenic effect of the chitosan membranes via mutual crosslinking using a crosslinker (EDC, 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide). The morphology of PS-CS membranes was shown by scanning electron microscopy (SEM) to have an interconnected porous structure. The incorporation of phosphoserine into chitosan membranes was confirmed by energy dispersive spectrum (EDS), Fourier Transforms Infrared (FTIR), and X-ray diffraction (XRD) spectrum. The CCK8 assay and Live/Dead staining, Hemolysis analysis, and cell adhesion assay demonstrated that PS-CS membranes had good biocompatibility. The osteogenesis-related gene expression of BMSCs was higher in PS-CS membranes than in CS membranes, which was verified by alkaline phosphatase (ALP) activity, immunofluorescence staining, and real-time quantitative PCR (RT-qPCR). Furthermore, micro-CT and histological analysis of rat cranial bone defect demonstrated that PS-CS membranes dramatically stimulated bone regeneration in vivo. Moreover, H&E staining of the main organs (heart, liver, spleen, lung, or kidney) showed no obvious histological abnormalities, revealing that PS-CS membranes were no additional systemic toxicity in vivo. Collectively, PS-CS membranes may be a promising candidate for bone tissue engineering.
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Spinal cord injury (SCI) is a devastating injury that causes permanent loss of sensation and motor function. SCI repair is a significant challenge due to the limited regenerating ability of adult neurons and the complex inflammatory microenvironment. After SCI, the oxidative stress induced by excessive reactive oxygen species (ROS) often leads to prolonged neuroinflammation that results in sustained damage to the spinal cord tissue. Polydopamine (PDA) shows remarkable capability in scavenging ROS to treat numerous inflammatory diseases. In this study, glial cell-derived neurotrophic factor (GDNF)-loaded PDA nanoparticle-based anisotropic scaffolds for spinal cord repair are developed. It is found that mesoporous PDA nanoparticles (mPDA NPs) in the scaffolds efficiently scavenge ROS and promote microglia M2 polarization, thereby inhibiting inflammatory response at the injury site and providing a favorable microenvironment for nerve cell survival. Furthermore, the GDNF encapsulated in mPDA NPs promotes corticospinal tract motor axon regeneration and its locomotor functional recovery. Together, findings from this study reveal that the GDNF-loaded PDA/Gelatin scaffolds hold potential as an effective artificial transplantation material for SCI treatment.
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Nanopartículas , Traumatismos de la Médula Espinal , Regeneración de la Medula Espinal , Axones , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Especies Reactivas de Oxígeno , Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico , HumanosRESUMEN
Tetracycline is extensively used as an antibiotic in animal husbandry, and there arose an increase in antibiotic resistance genes in the environment, posing a threat to human health. Motivated by this, a magnetic molecularly imprinted material based on synergistic recognition (1 + 1>2) was constructed and coupled with high-performance liquid chromatography to detect ultra-trace tetracycline in complicated samples. In this case, the molecularly imprinted polymers were synthesized via a "one-pot" method and acted as recognition elements on the surface of silica-coated ferroferric oxide particles. Aptamers and ß-cyclodextrin, as functional monomers, had a synergistic effect on the recognition of tetracycline and the synergistic recognition factor was 1.7. Meanwhile, the material exhibited high selectivity to tetracycline with an imprinting factor of 7.6. In addition, compared to being modified on the surface, the stability of the aptamers was effectively improved by cross-linking in the molecularly imprinted polymer framework. Relevant experimental conditions, such as buffers, concentration of magnesium ions and adsorption time, were optimized. As a result, the method showed a limit of detection of 1.0 µg L-1 and the linearity range of 0.005-0.5 mg L-1, as well as certain reproducibility and stability. Furthermore, when applied for the analysis of animal feed samples, a significant reduction of matrix interference was observed with satisfactory recoveries (85.0-111.5%), which emphasized the good accuracy and practicability of the established method. For these advantages, the proposed method represents a versatile and powerful tool for the separation and detection of small molecule compounds in complicated real samples.
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Impresión Molecular , beta-Ciclodextrinas , Animales , Humanos , Polímeros Impresos Molecularmente , Impresión Molecular/métodos , Reproducibilidad de los Resultados , Polímeros/química , Tetraciclina , Antibacterianos , Fenómenos MagnéticosRESUMEN
Because of the limited regenerative ability of the central nervous system (CNS), effective treatments for spinal cord injury (SCI) are still lacking. After SCI, neuron loss and axon regeneration failure often result in irreversible functional impairment. The calcium overload induced by the N-methyl-D-aspartate receptor (NMDAR) overactivation is critical for cell death in SCI. It has been reported that the magnesium ion (Mg2+ ) can competitively block the NMDAR and reduce the calcium influx, and that sonic hedgehog (Shh) and retinoic acid (RA) are the critical regulators of neuronal differentiation of endogenous neural stem cells (NSCs). Here, magnesium oxide (MgO)/poly (l-lactide-co-ε-caprolactone) (PLCL) scaffold loaded with purmorphamine (PUR, a Shh signaling agonist) and RA is developed and its feasibility in SCI repair is tested. The results showed that the Mg2+ released from MgO attenuated cell apoptosis by blocking the calcium influx, and the PUR/RA promoted the recruitment and neuronal differentiation of endogenous NSCs, thereby reducing the glial scar formation at the SCI lesion site. Furthermore, implantation of PUR/RA-loaded MgO/PLCL scaffold facilitates the partial recovery of a locomotor function of SCI mouse in vivo. Together, findings from this study imply that PUR/RA-loaded MgO/PLCL scaffold may be a promising biomaterial for the clinical treatment of SCI.
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Células-Madre Neurales , Traumatismos de la Médula Espinal , Regeneración de la Medula Espinal , Animales , Axones/metabolismo , Calcio/metabolismo , Caproatos , Diferenciación Celular , Dioxanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacología , Lactonas , Óxido de Magnesio/metabolismo , Óxido de Magnesio/farmacología , Ratones , Médula Espinal/patología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Andamios del TejidoRESUMEN
This study aimed to explore the psychological mechanisms behind the relationship between kindergarten parental satisfaction and parental loyalty. This study used the parental satisfaction scale, parental trust scale, parental relationship commitment scale, and parental loyalty scale on 923 kindergarten parents. The test was conducted on 923 kindergarten parents. The results of this study showed that parental satisfaction significantly and positively affected parental loyalty. Parental trust was partially mediated between parental satisfaction and parental loyalty. Parental relationship commitment was also partially mediated between parental satisfaction and parental loyalty. Regarding to parental satisfaction and parental loyalty, parental trust and parental relationship commitment had chain mediation effect between parental satisfaction and parental loyalty. The findings of this study provided valuable insights into the effect of parental satisfaction on parental loyalty and offer concrete practical suggestions for kindergarten operators to improve the loyalty of kindergarten parents.
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Neural precursor cells (NPCs) generate new neurons to supplement neuronal loss as well as to repair damaged neural circuits. Therefore, NPCs have potential applications in a variety of neurological diseases, such as spinal cord injury, traumatic brain injury, and glaucoma. Specifically, improving NPCs proliferation and manipulating their differentiated cell types can be a beneficial therapy for a variety of these diseases. ADT-OH is a slow-releasing organic H2 S donor that produces a slow and continuous release of H2 S to maintain normal brain functions. In this study, we aimed to explore the effect of ADT-OH on NPCs. Our results demonstrated that ADT-OH promotes self-renewal and antiapoptosis ability of cultured NPCs. Additionally, it facilitates more NPCs to differentiate into neurons and oligodendrocytes, while inhibiting their differentiation into astrocytes. Furthermore, it enhances axonal growth. Moreover, we discovered that the mRNA and protein expression of ß-catenin, TCF7L2, c-Myc, Ngn1, and Ngn2, which are key genes that regulate NPCs self-renewal and differentiation, were increased in the presence of ADT-OH. Altogether, these results indicate that ADT-OH may be a promising drug to regulate the neurogenesis of NPCs, and needs to be studied in the future for clinical application potential.
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Sulfuro de Hidrógeno , Células-Madre Neurales , Animales , Diferenciación Celular , Células Cultivadas , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Mamíferos , Células-Madre Neurales/metabolismo , Neuronas , TionasRESUMEN
Background The aim of the study was to explore the potential role of IL-37 in nerve repair and immune regulation in peripheral nerve xenograft hosts. Methods Rat nerve xenografts were transplanted into mouse recipients. Transplanted mice received an intraperitoneal injection of IL-37 on the day before transplantation, whereas control mice remained untreated. At postoperative 2, 4, 8, and 12 weeks, the effects of IL-37 were examined on motor function, tissue morphology, and regenerative ability of xenograft nerves. Levels of IL-17 and IL-22 in serum and spleen were measured at 3, 7, 14, and 28 days after nerve transplantation. Results At 12 postoperative weeks, grafted nerves grew well in IL-37 treatment group, as documented by the recovery in function of sciatic nerves compared to untreated controls. In particular, IL-37-treated mice showed more complete neuromorphology, thicker myelin sheath, compact structure, and the increased number of myelinated nerve fibers in histological examination. The number of T helper (Th)17 (CD3 + CD4 + IL-17+) and Th22 (CD3 + CD4 + IL-22+) cells in the spleen was reduced in the IL-37-treated group, as well as serum IL-17 and IL-22 were decreased after IL-37 treatment compared with the untreated group. Conclusions IL-37 attenuates immunomodulatory responses induced by xenografts, contributing to the recovery of nerve function and the prevention of muscle atrophy caused by nerve grafts.
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Interleucina-17 , Interleucinas , Animales , Xenoinjertos , Humanos , Ratones , Ratas , Nervio Ciático , Trasplante HeterólogoRESUMEN
Let-7 miRNA family has been proved as a key regulator of mesenchymal stem cells' (MSCs') biological features. However, whether let-7b could affect the differentiation or proliferation of periodontal ligament stem cells (PDLSCs) is still unknown. Here, we found that the expression of hsa-let-7b was visibly downregulated after mineralization induction of PDLSCs. After transfected with hsa-let-7b mimics or inhibitor reagent, the proliferation ability of PDLSCs was detected by cell counting kit-8 (CCK-8), flow cytometry, and 5-ethynyl-2-deoxyuridine (EdU) assay. On the other hand, the osteogenic differentiation capacity was detected by alkaline phosphatase (ALP) staining and activity, alizarin red staining, Western blot, and quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). We verified that hsa-let-7b did not significantly impact the proliferation ability of PDLSCs, but it could curb the osteogenic differentiation of PDLSCs. Besides, we predicted CTHRC1 acts as the downstream gene of hsa-let-7b to affect this process. Moreover, the combination of CTHRC1 and hsa-let-7b was verified by dual luciferase reporter assay. Our results demonstrated that the osteogenic differentiation of PDLSCs was enhanced after inhibiting hsa-let-7b, while was weakened after cotransfection with Si-CTHRC1. Collectively, hsa-let-7b can repress the osteogenic differentiation of PDLSCs by regulating CTHRC1.
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Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3ß/ß-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.
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Carcinoma Pulmonar de Lewis , Medicamentos Herbarios Chinos/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , beta Catenina/metabolismo , Animales , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Metástasis de la NeoplasiaRESUMEN
Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).
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Glioma is the most common and deadly tumor in central nervous system. According to previous studies, long noncoding RNAs (lncRNA) and transcription factors were significant factors of gliomas progression by regulating gliomas immune microenvironment. In our study, we built two independent cohorts from CGGA and TCGA. And we extracted 253 immune-related lncRNA correlated with prognosis. After LASSO analysis and multivariate Cox regression analysis, 8 immune-related lncRNA were used to construct classifier. The effectiveness of classifier was confirmed in both CGGA (AUC = 0.869) and TCGA (AUC = 0.902) cohorts. The correlation between transcription factors and immune-related lncRNA was calculated by WCGNA. Eventually, we built a network between 8 lncRNA and transcription factors. The function of core immune-related lncRNA in gliomas immune microenvironment was also investigated by CIBERTSORT. Our research provided a strong classifier of immune-related lncRNA to predict gliomas patient outcome. We also found the correlation between core immune-related lncRNA and transcription factors. These results may stimulate new strategy of immunotherapy in gliomas patients.
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PURPOSE: Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, has potent antitumor properties, but the molecular mechanism is still unclear. The aim of the study was to investigate the antitumor mechanism of XJR on hepatocellular carcinoma (HCC) by focusing on miRNA. METHODS: Three concentrations of XJR (low, middle, and high) were used to treat tumor xenograft mice models. Microarray technology was used to identify the differential expressed genes after XJR treatment, and bioinformatic tools and luciferase reporter assay to predict the potential pathways. HepG2 cells were transfected with inhibitor of miR-200b-3p to detect the effect of miR-200b-3p and Notch1 on tumor growth. RESULTS: XJR effectively exerted anti-HCC effect both in vitro and in vivo. MiRNA chip analysis results showed that the expression of 75 miRNAs was upregulated and 158 miRNAs was downregulated in blood from XJR-treated mice. Further validation by using real-time polymerase chain reaction (RT-PCR) assay showed that the expression of five miRNAs (miR-453, miR-200b-3p, miR-135a-1-3p, miR-1960, miR-378a-5p, and miR-466f) was consistent with the results of miRNA chip analysis. Among them, miR-200b-3p was selected as candidate for further research. Results of the MTT, migration, and wound healing assays showed that down-expression of miR-200b-3p abrogated the effect of XJR on cell growth and metastasis. Luciferase reporter assay confirmed that Notch1 was the direct target of miR-200b-3p. XJR significantly decreased Notch1 expression in HepG2 cells, whereas miR-200B-3p inhibitor abrogated the XJR-induced decrease in Notch1 expression. CONCLUSION: This study indicated that XJR could effectively inhibit HCC and might exert its antitumor effect through the miR-200b-3p/Notch1 axis. These findings provided new avenues for the use of XJR for prevention and treatment of HCC.