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2.
Small ; : e2312148, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438906

RESUMO

Iron-based perovskite air electrodes for protonic ceramic cells (PCCs) offer broad application prospects owing to their reasonable thermomechanical compatibility and steam tolerance. However, their insufficient electrocatalytic activity has considerably limited further development. Herein, oxygen-vacancy-rich BaFe0.6 Ce0.2 Sc0.2 O3-δ (BFCS) perovskite is rationally designed by a facile Sc-substitution strategy for BaFe0.6 Ce0.4 O3-δ (BFC) as efficient and stable air electrode for PCCs. The BFCS electrode with an optimized Fe 3d-eg orbital occupancy and more oxygen vacancies exhibits a polarization resistance of ≈ 0.175 Ω cm2 at 600 °C, ≈ 1/3 of the BFC electrode (≈0.64 Ω cm2 ). Simultaneously, BFCS shows favorable proton uptake with a low proton defect formation enthalpy (- 81 kJ mol-1 ). By combining soft X-ray absorption spectroscopy and electrical conductivity relaxation studies, it is revealed that the enhancement of Fe4+ -O2- interactions in BFCS promotes the activation and mobility of lattice oxygen, triggering the activity of BFCS in both oxygen reduction and evolution reactions (ORR/OER). The single cell achieves encouraging output performance in both fuel cell (1.55 W cm-2 ) and electrolysis cell (-2.96 A cm-2 at 1.3 V) modes at 700 °C. These results highlight the importance of activating lattice oxygen in air electrodes of PCCs.

4.
Small ; 20(15): e2304574, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38009795

RESUMO

Direct selective transformation of greenhouse methane (CH4) to liquid oxygenates (methanol) can substitute energy-intensive two-step (reforming/Fischer-Tropsch) synthesis while creating environmental benefits. The development of inexpensive, selective, and robust catalysts that enable room temperature conversion will decide the future of this technology. Single-atom catalysts (SACs) with isolated active centers embedded in support have displayed significant promises in catalysis to drive challenging reactions. Herein, high-density Ni single atoms are developed and stabilized on carbon nitride (NiCN) via thermal condensation of preorganized Ni-coordinated melem units. The physicochemical characterization of NiCN with various analytical techniques including HAADF-STEM and X-ray absorption fine structure (XAFS) validate the successful formation of Ni single atoms coordinated to the heptazine-constituted CN network. The presence of uniform catalytic sites improved visible absorption and carrier separation in densely populated NiCN SAC resulting in 100% selective photoconversion of (CH4) to methanol using H2O2 as an oxidant. The superior catalytic activity can be attributed to the generation of high oxidation (NiIII═O) sites and selective C─H bond cleavage to generate •CH3 radicals on Ni centers, which can combine with •OH radicals to generate CH3OH.

5.
Front Surg ; 10: 1177280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304181

RESUMO

Background: Surgical intervention is necessary for resolving the symptoms of the spinal cord and nerve compression caused by symptomatic metastatic epidural spinal cord compression. However, surgeons are constantly seeking ways to improve surgical efficiency and safety. This study aims to evaluate the efficacy of 3D simulation/printing-assisted surgery for symptomatic metastatic epidural spinal cord compression of the posterior column. Methods: We retrospectively analyzed the clinical data of patients who underwent surgical treatment for symptomatic metastatic epidural spinal cord compression of the posterior column in our hospital from January 2015 to January 2020. The simulated group underwent a 3D digital simulation of the lesion area using imaging data before surgery. Twelve patients in the simulated group also received 3D printing, while the direct surgery group did not receive any 3D simulation or printing. All patients were followed up for at least 2 years. We collected clinical data, including operation time, intraoperative blood loss, pedicle screw adjustment rate, intraoperative fluoroscopy times, the incidence of dural injury and cerebrospinal fluid leakage, VAS score, postoperative neurological function improvement, and tumor recurrence. Statistical analysis was performed using SPSS23.0, and P < 0.05 was considered statistically significant. Results: A total of 46 patients were included in this study, with 20 in the simulated group and 26 in the non-simulated group. The simulated group had better operation time, intraoperative blood loss, screw adjustment rate, fluoroscopy times, and incidence of dural injury/cerebrospinal fluid leakage compared to the non-simulated group. The VAS scores of the two groups improved significantly after the operation and at the last follow-up compared to before the operation. However, there was no statistically significant difference between the two groups. There was also no statistically significant difference in neurological function improvement between the two groups. In the simulated group, 25% of patients relapsed, while in the non-simulated group, 34.61% of patients relapsed. However, there was no statistical difference between the two groups. Conclusion: Preoperative 3D simulation/printing-assisted surgery is a practical and feasible approach for treating symptomatic metastatic epidural spinal cord compression of the posterior column.

6.
Nutr Res Rev ; : 1-12, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37088535

RESUMO

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.

7.
J Neurosurg Sci ; 67(6): 718-726, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33709660

RESUMO

BACKGROUND: This retrospective study aimed to perform a comparative evaluation of the mid- to long-term efficacy of long-segment and short-segment fixations via the posterior approach as a treatment for tuberculous spondylodiscitis in the mid-thoracic spine. METHODS: A total of 95 patients with tuberculous spondylodiscitis in the mid-thoracic spine underwent surgery via the posterior approach including single-stage posterior debridement, interbody fusion, and pedicle screw fixation. Long-segment fixations were performed for 46 patients (group A), while short-segment fixations were performed for the other 49 patients (group B). Clinical and radiological outcomes were assessed during mid- to long-term follow-up. RESULTS: The average follow-up periods for groups A and B were 75.5±11.8 and 76.8±11.6 months, respectively. The operative time and intraoperative blood loss were lower in group B than in group A (P<0.05). Both management approaches significantly corrected the kyphotic deformity detected either in the early postoperative period or at the final visit after long-term follow-up (P>0.05). Bony fusion was generated after average periods of 10.8±2.1 months and 11.0±2.0 months in groups A and B, respectively. Favorable outcomes were observed on assessment of neurological function and patients' well-being at the final follow-up. CONCLUSIONS: No therapeutic differences were observed between long-segment and short-segment fixation as surgical treatment for mid-thoracic Pott's disease during mid- to long-term follow-up. Kyphotic deformity and neurological impairment were significantly relieved via both posterior fixation approaches, with patients' well-being reaching a favorable level. Moreover, short-segment fixation led to less blood loss and required a shorter operative time.


Assuntos
Discite , Cifose , Fusão Vertebral , Humanos , Adulto , Discite/cirurgia , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Vértebras Torácicas/cirurgia , Resultado do Tratamento
8.
J Hepatol ; 78(3): 627-642, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36462680

RESUMO

BACKGROUND & AIMS: Alterations of multiple metabolites characterize distinct features of metabolic reprograming in hepatocellular carcinoma (HCC). However, the role of most metabolites, including propionyl-CoA (Pro-CoA), in metabolic reprogramming and hepatocarcinogenesis remains elusive. In this study, we aimed to dissect how Pro-CoA metabolism affects these processes. METHODS: TCGA data and HCC samples were used to analyze ALDH6A1-mediated Pro-CoA metabolism and its correlation with HCC. Multiple metabolites were assayed by targeted mass spectrometry. The role of ALDH6A1-generated Pro-CoA in HCC was evaluated in HCC cell lines as well as xenograft nude mouse models and primary liver cancer mouse models. Non-targeted metabolomic and targeted energy metabolomic analyses, as well as multiple biochemical assays, were performed. RESULTS: Decreases in Pro-CoA and its derivative propionyl-L-carnitine due to ALDH6A1 downregulation were tightly associated with HCC. Functionally, ALDH6A1-mediated Pro-CoA metabolism suppressed HCC proliferation in vitro and impaired hepatocarcinogenesis in mice. The aldehyde dehydrogenase activity was indispensable for this function of ALDH6A1, while Pro-CoA carboxylases antagonized ALDH6A1 function by eliminating Pro-CoA. Mechanistically, ALDH6A1 caused a signature enrichment of central carbon metabolism in cancer and impaired energy metabolism: ALDH6A1-generated Pro-CoA suppressed citrate synthase activity, which subsequently reduced tricarboxylic acid cycle flux, impaired mitochondrial respiration and membrane potential, and decreased ATP production. Moreover, Pro-CoA metabolism generated 2-methylcitric acid, which mimicked the inhibitory effect of Pro-CoA on citrate synthase and dampened mitochondrial respiration and HCC proliferation. CONCLUSIONS: The decline of ALDH6A1-mediated Pro-CoA metabolism contributes to metabolic remodeling and facilitates hepatocarcinogenesis. Pro-CoA, propionyl-L-carnitine and 2-methylcitric acid may serve as novel metabolic biomarkers for the diagnosis and treatment of HCC. Pro-CoA metabolism may provide potential targets for development of novel strategies against HCC. IMPACT AND IMPLICATIONS: Our study presents new insights on the role of propionyl-CoA metabolism in metabolic reprogramming and hepatocarcinogenesis. This work has uncovered potential diagnostic and predictive biomarkers, which could be used by physicians to improve clinical practice and may also serve as targets for the development of therapeutic strategies against HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Citrato (si)-Sintase , Carnitina/metabolismo , Carnitina/farmacologia
9.
Orthop Surg ; 15(1): 53-61, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36222206

RESUMO

OBJECTIVE: Mid-thoracic spinal tuberculosis is prone to kyphotic deformities and neurologic impairment. Posterior approach can effectively restore the spinal stability by reconstructing the anterior and middle spinal columns. Titanium mesh cages (TMC), allogeneic bone (ALB), and autogenous bone (AUB) are three main bone graft struts. We aimed to compare the therapeutic efficacy of three bone graft struts, for anterior and middle column reconstruction through a posterior approach in cases of mid-thoracic spinal tuberculosis. METHODS: Hundred and thirty seven patients with thoracic spinal tuberculosis who had undergone a posterior approach from June 2010 to December 2018 were enrolled. Of them, 46 patients were treated using a titanium mesh cage (TMC group), 44 with allogenic bone grafts (ALB group), and 47 using autogenous bone grafts (AUB group). The following were analyzed to evaluate clinical efficacy: visual analogue scale (VAS) values, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, kyphotic Cobb's angle, operation duration, intraoperative blood loss, improvement in American Spinal Injury Association (ASIA) grade and in the mental component summary (MCS) and physical component summary (PCS) of Short Form-36 (SF-36), duration of bone graft fusion. The data of the three groups were compared by way of variance analysis, followed by the LSD⁃t test to compare each group. A repeated measures ANOVA was used to analyze the dates of pre-, postoperative and final follow-up. RESULTS: The follow-up duration was at least 3 years. All patients achieved a complete cure for spinal TB. Neurological performance and quality of life were remarkably improved at the final follow-up. The intraoperative blood loss, operation time and VAS values 1 day postoperatively for TMC group and ALB group were significantly lower than those in AUB group (P < 0.05). The duration of bone graft fusion in ALB group (18.1 ± 3.7 months) was longer than that in TMC group and AUB group (9.5 ± 2.8 and 9.2 ± 1.9 months) (P < 0.05). No significant intergroup differences were observed in terms of age or preoperative, 3-months postoperative, and final follow-up indices of ESR and CRP among the three groups (P > 0.05). At the final follow-up, the correction loss was mild (2.1 ± 0.9, 2.2 ± 1.0, 2.1 ± 0.8) and Cobb's angles of the three groups were 20.1 ± 2.9, 20.5 ± 3.2, 20.9 ± 3.4, respectively, which were remarkably rectified in comparison with the preoperative measurements (P < 0.05). CONCLUSIONS: In terms of postoperative recovery and successful fusion rate of bone graft, it seems that posterior instrumentation, debridement, and interbody fusion with titanium mesh cages are more effective and appropriate surgical methods for mid-thoracic spinal tuberculosis.


Assuntos
Cifose , Fusão Vertebral , Tuberculose da Coluna Vertebral , Humanos , Lactente , Tuberculose da Coluna Vertebral/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Titânio , Perda Sanguínea Cirúrgica , Qualidade de Vida , Vértebras Torácicas/cirurgia , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Cifose/cirurgia , Desbridamento/métodos
10.
Biomed Res Int ; 2022: 4072975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467885

RESUMO

Bone defect repair remains a challenge in orthopedics. This study describes the development and potential effectiveness of vascular endothelial growth factor (VEGF)/bone morphogenetic protein-2 (BMP-2) shell-core microspheres for promoting bone regeneration. Poly(L-lactic acid)/polylactic-co-glycolic acid (PLLA/PLGA) core-shell microspheres loaded with VEGF and BMP-2 were prepared by a coaxial electrospray technique, and their surface morphology, core-shell distribution, and particle size were examined. Different groups of microspheres were prepared with different placement of the growth factors, and the encapsulation efficiency and in vitro release curves were measured. Additionally, the effects of the different groups of microspheres on the proliferation and differentiation of osteoblasts and vascular endothelial cells were investigated. The prepared microspheres had a core-shell structure with good homogeneity and dispersion, a clear boundary, and a smooth surface. On scanning electron microscopy, the mean diameter of the microspheres was similar for all six preparations (P > 0.05). During in vitro release, growth factor was initially released via a brief burst release from the outer shell of the microsphere followed by a slower sustained release. The release of growth factors from the inner core remained relatively slow and sustained. Sequential release of different growth factors was achieved through the inconsistent release rates from the microsphere shell and inner core. All groups of microspheres showed no cytotoxicity, good biocompatibility, and the ability to promote osteoblast proliferation. The microspheres loaded with BMP-2 also promoted osteoblast differentiation, and VEGF-loaded microspheres promoted the proliferation and differentiation of vascular endothelial cells. The BMP-2 (core)/VEGF (shell) microsphere group best promoted osteoblast differentiation. The microspheres prepared in this study exhibited slow sequential release of BMP-2 and VEGF and showed good biocompatibility along with the ability to promote osteoblast differentiation and vascular endothelial cell proliferation.


Assuntos
Células Endoteliais , Fator A de Crescimento do Endotélio Vascular , Microesferas , Preparações de Ação Retardada/farmacologia , Fatores de Crescimento do Endotélio Vascular
11.
Cell Oncol (Dordr) ; 45(6): 1187-1202, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327092

RESUMO

PURPOSE: Dysregulated cell cycle targeting is a well-established therapeutic strategy against hepatocellular carcinoma (HCC). Dissecting the underlying mechanism may improve the efficacy of HCC therapy. METHODS: HCC data from TCGA and new clinical samples were used for DNASE1L3 expression analysis and for assessing its correlation with HCC development. The in vitro function of DNASE1L3 in HCC cell proliferation, colony formation, migration and invasion was assessed using RTCA, CCK-8 and transwell assays and the in vivo function in subcutaneous tumor formation in a xenograft nude mouse model. The role of DNASE1L3 in HCC tumorigenesis was further verified in AKT/NRASV12-induced and DEN/CCl4-induced primary liver cancers in wildtype and Dnase1l3-/- mice. Finally, RNA-Seq analysis followed by biochemical methods including cell cycle, immunofluorescence, co-immunoprecipitation and Western blotting assays were employed to reveal the underlying mechanism. RESULTS: We found that DNASE1L3 was significantly downregulated and served as a favorable prognostic factor in HCC. DNASE1L3 dramatically attenuated HCC cell proliferation, colony formation, migration and invasion in vitro and reduced subcutaneous tumor formation in nude mice in vivo. Furthermore, DNASE1L3 overexpression dampened AKT/NRASV12-induced mouse liver cancer in wildtype mice and DNASE1L3 deficiency worsened DEN/CCl4-induced liver cancer in Dnase1l3-/- mice. Systemic analysis revealed that DNASE1L3 impaired HCC cell cycle progression by interacting with CDK2 and inhibiting CDK2-stimulated E2F1 activity. C-terminal deletion (DNASE1L3ΔCT) diminished the interaction with CDK2 and abrogated the inhibitory function against HCC. CONCLUSION: Our study unveils DNASE1L3 as a novel HCC cell cycle regulator and tumor suppressor. DNASE1L3 impairs HCC tumorigenesis by delaying cell cycle progression possibly through disrupting the positive E2F1-CDK2 regulatory loop. DNASE1L3 may serve as a target for the development of novel therapeutic strategies against HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Ciclo Celular/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Modelos Animais de Doenças , Proliferação de Células/genética , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Endodesoxirribonucleases/metabolismo
12.
Connect Tissue Res ; 63(6): 634-649, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35603476

RESUMO

OBJECTIVE: This study investigated the molecular mechanism of whether hUC-MSCs-EVs repressed PTEN expression and activated the PI3K/AKT pathway through miR-29b-3p, thus inhibiting LPS-induced neuronal injury. METHODS: hUC-MSCs were cultured and then identified. Cell morphology was observed. Alizarin red, oil red O, and alcian blue staining were used for inducing osteogenesis, adipogenesis, and chondrogenesis. EVs were extracted from hUC-MSCs and identified by transmission electron microscope observation and Western blot. SCI neuron model was established by 24h lipopolysaccharide (LPS) induction. After the cells were cultured with EVs without any treatment, uptake of EVs by SCI neurons, miR-29b-3p expression, cell viability, apoptosis, caspase-3, cleaved caspase-3, caspase 9, Bcl-2, PTEN, PI3K, AKT, and p-Akt protein levels, caspase 3 and caspase 9 activities, and inflammatory factors IL-6 and IL-1ß levels were detected by immunofluorescence labeling, RT-qPCR, MTT, flow cytometry, Western blot, caspase 3 and caspase 9 activity detection kits, and ELISA. The binding sites between PTEN and miR-29b-3p were predicted by the database and verified by dual-luciferase assay. RESULTS: LPS-induced SCI cell model was successfully established, and hUC-MSCs-EVs inhibited LPS-induced apoptosis of injured spinal cord neurons. EVs transferred miR-29b-3p into LPS-induced injured neurons. miR-29b-3p silencing reversed EV effects on reducing LPS-induced neuronal apoptosis. miR-29b-3p reduced LPS-induced neuronal apoptosis by targeting PTEN. After EVs-miR-inhi and si-PTEN treatment, inhibition of the PI3K/AKT pathway reversed hUC-MSCs-EVs effects on reducing LPS-induced neuronal apoptosis. CONCLUSION: hUC-MSCs-EVs activated the PI3K/AKT pathway by carrying miR-29b-3p into SCI neurons and silencing PTEN, thus reducing neuronal apoptosis.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Traumatismos da Medula Espinal , Azul Alciano/metabolismo , Azul Alciano/farmacologia , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Caspase 9/farmacologia , Vesículas Extracelulares/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/metabolismo , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia , Cordão Umbilical/metabolismo
13.
BMC Musculoskelet Disord ; 23(1): 126, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135516

RESUMO

BACKGROUND: This retrospective study aimed to determine the feasibility and efficacy of endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion in patients with upper cervical spine tuberculosis. METHODS: Between June 2008 and January 2016, 17 patients (10 men and 7 women) with upper cervical spine tuberculosis underwent endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion. Anti-tuberculosis treatment was administered for 2-4 weeks preoperatively and 12-18 months postoperatively. The clinical and radiographic data of the patients were analyzed. RESULTS: The operation was successfully completed in all patients. Neck pain and stiffness were relieved after the surgery in all patients. The mean operation time was 210.0 ± 21.2 min, and the mean intraoperative blood loss was 364.7 ± 49.6 mL. The mean follow-up duration was 68.1 ± 6.7 months. The erythrocyte sedimentation rate returned to normal by 3 months postoperatively. Visual analog scale scores for neck pain were significantly lower postoperatively than preoperatively. All patients had significant postoperative neurological improvement. Patient-reported outcomes, as measured using the Kirkaldy-Willis criteria, were as follows: excellent, 12 patients; good, 4 patients; fair, 1 patient; and poor, 0 patients. Bone fusion was achieved at 10.9 ± 1.9 months after the surgery; no cases of instrument loosening or fracture occurred. CONCLUSION: Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion is a feasible and effective surgical method for the treatment of upper cervical spine tuberculosis. It can be used to restore upper cervical spine stability and facilitate spinal healing.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Desbridamento , Endoscopia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Vértebras Torácicas , Resultado do Tratamento , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/cirurgia
14.
Transl Oncol ; 15(1): 101245, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34678588

RESUMO

Clinic therapy of acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategies. Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for leukemia therapy. To target ANP32A, we identified a peptide that competed with ANP32A to bind to histone 3 (termed as H3-binding peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in leukemia cells. Furthermore, a synthesized membrane-penetrating peptide TAT-H3BP effectively entered into leukemia cells and phenocopied such effect. In vivo, TAT-H3BP showed potent efficacy against leukemia: Intra-tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells. Our findings demonstrate that intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML.

15.
J Biomed Mater Res A ; 110(4): 873-883, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34816584

RESUMO

Following recent advances in osteoimmunology, there is growing recognition of the vital role of immune cells in the osteogenesis process. The 3D-printed scaffold, as a substitute for injured and/or diseased bone tissues, has demonstrated satisfactory pro-osteogenetic performance. However, whether immune cells prompt the above pro-osteogenetic performance has not been elucidated in detail. In the present study, highly controllable Ti-6Al-4V scaffolds with different pore geometries were fabricated using a selective laser-melting technique, to reveal their osteoimmunological functions with macrophages. The results showed that macrophages displayed characteristics of M2 phenotype in response to scaffolds. As a result, an anti-inflammatory microenvironment was generated. When the pore geometry was considered, such observations were more apparent with the hexagonal pore scaffold than with the triangular one. In addition, inhibition of the toll-like receptor signaling pathway in macrophages has been proposed to cause the above phenomenon. Upon applying conditioned media derived from macrophages on pre-osteoblasts, the hexagonal pore scaffold group was found to significantly enhance osteoblastic differentiation, via macrophage-to-implant interactions. However, the effect of triangular pore scaffold was not statistically significant compared to that of hexagonal pore scaffolds or nonporous samples. In an attempt to quantify scaffold pore geometries, it was suggested that pores with higher circularity values tended to induce M2 polarization of macrophages, promote an anti-inflammatory milieu, and therefore, achieve better osteogenetic performance via immunomodulation.


Assuntos
Osteogênese , Titânio , Ligas , Lasers , Macrófagos , Porosidade , Alicerces Teciduais , Titânio/farmacologia
16.
Orthop Surg ; 13(7): 2051-2060, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34590777

RESUMO

OBJECTIVE: To evaluate the medium-term outcomes of one-stage posterior lumbosacral or lumbopelvic fixation treatment of lumbosacral junction tuberculosis in adults. METHODS: This retrospective study enrolled a total of 38 adult patients (24 males and 14 females) with an average age of 48.0 ± 13.0 years (range, 25-75 years) during the period from February 2008 to July 2015. All patients were treated by one-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage. After pedicle screw or iliac screw fixation, a hemi-laminectomy or laminectomy was performed on the severely damaged side of the lesion segment. Intervertebral bone grafting and intertransverse bone grafting were performed after clearing the focus of tuberculosis. All cases were followed up for at least 5 years. Intraoperative blood loss, operative time, erythrocyte sedimentation rate (ESR), pain intensity was assessed by visual analog scale (VAS) score; neurological function was assessed by Japanese Orthopaedic Association (JOA) score; quality of life was assessed by Oswestry Disability Index (ODI); functional outcome, lumbosacral angle, and fusion time were gathered and analyzed. All data expressed as mean ± standard deviation. RESULTS: During the 66.2 ± 4.4 months (range, 60-78 months) follow-up, all patients achieved clinical cure without severe complications. The intraoperative blood loss was 726.3 ± 151.9 mL (range, 400-1100 mL) and the operative time was 137.6 ± 22.5 min (range, 110-200 min). The ESR decreased to normal levels within (11.8 ± 2.6 mm/h) 3 months postoperatively. The VAS score significantly decreased from 6.8 ± 1.1 preoperatively to 0.8 ± 0.7 at the final follow-up (P < 0.01). The mean JOA improved from preoperative 18.5 ± 2.9 to 26.9 ± 1.1 at the last visit (P < 0.01). The mean ODI was 44.3 ± 6.7 and significantly decreased to 9.3 ± 1.9 at the final observation (P < 0.01). Patient-reported outcomes as measured by Kirkaldy-Willis criteria were excellent in 21 cases, good in 16 cases, and fair in one case; there were no poor outcomes. Lumbosacral angle increased from the preoperative values of 21.7° ± 1.8° to the postoperative values of 26.4° ± 1.4° (P < 0.01), with an angle loss of 1.2° ± 0.7° at the last follow-up. Bone fusion occurred on average 12.8 ± 1.9 months (range, 9-15 months) after surgery. No nonunion, pseudarthrosis, loosening or fracture of instruments occurred at the last follow-up. CONCLUSION: One-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage according to the severity of sacral destruction is an effective and highly safe procedure to treat lumbosacral junction tuberculosis in adults.


Assuntos
Desbridamento/métodos , Laminectomia/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Tuberculose da Coluna Vertebral/cirurgia , Adulto , Idoso , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos
17.
Cancer Control ; 28: 10732748211004880, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759598

RESUMO

Pediatric solid tumors are heterogeneous and comprise various histological subtypes. TP53, a tumor suppressor, orchestrates the transcriptional activation of anti-cancer genes. The gene coding for this protein is highly polymorphic, and its mutations are associated with cancer development. The Arg72Pro polymorphism in TP53 has been associated with susceptibility to various types of cancer. Here, in this hospital-based study, we evaluated the association of this polymorphism with susceptibility toward malignant abdominal solid tumors in children in the Hunan province of China. We enrolled 162 patients with neuroblastoma, 60 patients with Wilms' tumor, and 28 patients with hepatoblastoma as well as 270 controls. Genotypes were determined using a TaqMan assay, and the strength of the association was assessed using an odds ratio, within a 95% confidence interval identified using logistic regression models. Our results showed that the Arg72Pro polymorphism did not exhibit significant association with susceptibility toward pediatric malignant abdominal solid tumors. Stratification analysis revealed that this polymorphism exerts weak sex- and age-specific effects on Wilms' tumor and hepatoblastoma susceptibility, respectively. Overall, our results indicate that the Arg72Pro polymorphism may have a marginal effect on susceptibility toward pediatric malignant abdominal solid tumors in Hunan, and this finding warrants further confirmation.


Assuntos
Neoplasias Abdominais/genética , Neuroblastoma/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Arginina/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
BMC Musculoskelet Disord ; 22(1): 213, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33612112

RESUMO

BACKGROUND: To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia. METHODS: Data on 118 active thoracic spinal TB patients with paraparesis and paraplegia who had undergone surgery at an early stage (within three weeks of paraparesis and paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade and NASCIS score of neurological status rating, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb's angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects of surgery. RESULTS: The mean operating time was 194.2 minutes, and the mean blood loss was 871.2 ml. The perioperative complication rate was 5.9 %. The mean preoperative VAS score was 5.3, which significantly decreased to 3.2 after the operation and continued decreasing to 1.1 at follow up (P<0.05). All cases achieved an increase of at least one ASIA grade after operation. The rate of full neurological recovery for paraplegia (ASIA grade A and B) was 18.0 % and was significantly lower than the rate (100 %) for paraparesis (ASIA grade C and D) (P<0.05). On the NASCIS scale, the difference in the neurological improvement rate between paraplegia (22.2 % ± 14.1 % in sensation and 52.2 % ± 25.8 % in movement) and paraparesis (26.7 % ± 7.5 % in sensation and 59.4 % ± 7.3 % in movement) was remarkable (P<0.05). Mean preoperative ESR and CRP were 73.1 mm /h and 82.4 mg/L, respectively, which showed a significant increase after operation (P>0.05), then gradually decreased to 11.5 ± 1.8 mm/h and 2.6 ± 0.82 mg/L, respectively, at final follow up (P<0.05). The mean preoperative kyphotic Cobb's angle was 21.9º, which significantly decreased to 6.5º after operation (P<0.05) while kyphotic correction was not lost during follow up (P>0.05). The mean duration of bone graft fusion was 8.6 ± 1.3 months. CONCLUSIONS: Early surgical intervention may be beneficial for active thoracic spinal TB patients with paraparesis and paraplegia, with surgical intervention being more beneficial for recovery from paraparesis than paraplegia.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Desbridamento , Humanos , Vértebras Lombares , Paraparesia/etiologia , Paraplegia/diagnóstico , Paraplegia/etiologia , Estudos Retrospectivos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Tuberculose da Coluna Vertebral/complicações , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/cirurgia
19.
J Orthop Surg Res ; 15(1): 473, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054798

RESUMO

BACKGROUND: To evaluate the mid-long-term outcomes of surgical management of mono-segmental lumbar and lumbosacral spinal tuberculosis (TB) in adults by one-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion. METHODS: A total of 62 patients with mono-segmental lumbar or lumbosacral spinal tuberculosis were enrolled. One-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion was performed. Clinical and radiographic outcomes were compared and analyzed. RESULTS: All patients were followed-up for an average of 75.0 ± 11.5 months and completely cured at the final follow-up. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) returned to normal within three months postoperatively. Postoperative Japanese Orthopedic Association (JOA) score, visual analog scale (VAS) and Oswestry Disability index (ODI) were significantly improved compared with preoperative values. Bony fusion occurred after an average of 9.8 ± 2.6 months. The lordosis angle and lumbosacral angle were increased from preoperative 20.4 ± 2.9° and 14.7 ± 3.4° to postoperative 32.8 ± 3.6° and 22.4 ± 5.5°, with angle loss of 1.0 ± 0.7° and 0.8 ± 0.7° at the final follow-up, respectively. No significant differences between preoperative and postoperative adjacent segment disc height (DH) were found. CONCLUSIONS: One-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion represent effective and feasible treatment option for mono-segmental lumbar and lumbosacral spinal tuberculosis in adults. This approach may preserve lumbar normal motor units and decrease adjacent segment degeneration (ASD) with the advantages of minimal invasiveness and rapid postoperative rehabilitation.


Assuntos
Desbridamento/métodos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fusão Vertebral/métodos , Tuberculose da Coluna Vertebral/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Telas Cirúrgicas , Fatores de Tempo , Titânio , Resultado do Tratamento
20.
Cell Mol Biol (Noisy-le-grand) ; 66(3): 138-142, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32538760

RESUMO

This study aimed to compare the diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis. 40 healthy Balb/c nude mice were selected. 0.1 ml of human lung cancer cell A549 bacterial suspension was injected by the left ventricle injection method to establish a lung cancer spinal metastasis model, and the abnormal signs of the nude mice were closely observed. When the body weight was reduced by 20%, micro PET/CT imaging and small coil MRI imaging were applied after intraperitoneal injection of thiopental anesthesia in nude mice. After the imaging was completed, the nude mouse was dissected and the spinal tumor was removed. The nature of spinal metastases was diagnosed by the pathology department. 5 nude mice died of abdominal infection, 2 nude mice had no spinal tumors, and the remaining 33 nude mice were successfully modeled. 33 nude mice were confirmed by pathology to have 64 metastatic vertebral lesions, among them, there were 7 cervical vertebrae, 24 thoracic vertebrae, 16 lumbar vertebrae, 6 sacral vertebrae and 11 caudal vertebrae. The sensitivity of MRI in the diagnosis of spinal metastases was 78.13%, and specificity was 56.25%. The sensitivity of PET/CT for the diagnosis of spinal metastases was 92.19%, and specificity was 78.95%. The specificity and positive predictive value of PET/CT for the diagnosis of spinal metastases were not significantly different from those of MRI (P> 0.05). The sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). PET/CT is superior to MRI in the diagnosis of spinal metastases, and its sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). It is worthy to be further promoted in clinical practice.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Coluna Vertebral/secundário , Células A549 , Animais , Peso Corporal , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Camundongos Nus
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