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1.
Neural Regen Res ; 17(4): 824-831, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472482

RESUMO

Severe cerebral ischemia/reperfusion injury has been shown to induce high-level autophagy and neuronal death. Therefore, it is extremely important to search for a target that inhibits autophagy activation. Long non-coding RNA MEG3 participates in autophagy. However, it remains unclear whether it can be targeted to regulate cerebral ischemia/reperfusion injury. Our results revealed that in oxygen and glucose deprivation/reoxygenation-treated HT22 cells, MEG3 expression was obviously upregulated, and autophagy was increased, while knockdown of MEG3 expression greatly reduced autophagy. Furthermore, MEG3 bound miR-181c-5p and inhibited its expression, while miR-181c-5p bound to autophagy-related gene ATG7 and inhibited its expression. Further experiments revealed that mir-181c-5p overexpression reversed the effect of MEG3 on autophagy and ATG7 expression in HT22 cells subjected to oxygen and glucose deprivation/reoxygenation. In vivo experiments revealed that MEG3 knockdown suppressed autophagy, infarct volume and behavioral deficits in cerebral ischemia/reperfusion mice. These findings suggest that MEG3 knockdown inhibited autophagy and alleviated cerebral ischemia/reperfusion injury through the miR-181c-5p/ATG7 signaling pathway. Therefore, MEG3 can be considered as an intervention target for the treatment of cerebral ischemia/reperfusion injury. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Zhengzhou University, China (approval No. XF20190538) on January 4, 2019.

2.
Bioact Mater ; 7: 466-477, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466746

RESUMO

Small-diameter tissue-engineered vascular grafts (sdTEVGs) with hyperglycemia resistance have not been constructed. The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs. Here, inspired by bionic regulation of nerve on vascular, we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells (VSMCs). The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs. To address this concern, sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels. An external primary Reactive Oxygen Species (ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia. Then, the internal secondary ATP-responsive DENND1A (guanine nucleotide exchange factor) system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes. The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation. At day 90, the abnormal VSMCs phenotype was not detected in the sdTEVGs, which maintained long-time patency without intima hyperplasia. Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.

3.
Biomed Res Int ; 2021: 8328216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746310

RESUMO

Although hypoxia has been shown to promote keratinocyte migration and reepithelialization, the underlying molecular mechanisms remain largely unknown. ADAM17, a member of the metalloproteinase superfamily, has been implicated in a variety of cellular behaviors such as proliferation, adhesion, and migration. ADAM17 is known to promote cancer cell migration under hypoxia, and whether or how ADAM17 plays a role in hypoxia-induced keratinocyte migration has not been identified. Here, we found that ADAM17 expression and activity were significantly promoted in keratinocytes under hypoxic condition, inhibition of ADAM17 by TAPI-2, or silencing of ADAM17 using small interfering RNA which suppressed the hypoxia-induced migration of keratinocytes significantly, indicating a pivotal role for ADAM17 in keratinocyte migration. Further, we showed that p38/MAPK was activated by hypoxia. SB203580, an inhibitor of p38/MAPK, significantly attenuated the upregulation of ADAM17 as well as the migration of keratinocytes induced by hypoxia. Activation of p38/MAPK by MKK6 (Glu) overexpression, however, had adverse effects. Taken together, our study demonstrated that hypoxia-induced keratinocyte migration requires the p38/MAPK-ADAM17 signal axis, which sheds new light on the regulatory mechanisms of keratinocyte migration. Our study might also help in developing therapeutic strategies to facilitate wound healing in vivo, where cells are migrated in a hypoxic microenvironment.

4.
Orthop Surg ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816604

RESUMO

OBJECTIVE: To describe spinal osteotomy in lateral position, which might be a new strategy for correcting thoracolumbar kyphotic deformity combined with severe hip flexion contracture, and to present two cases in which this method was successfully performed. METHODS: Spinal osteotomies in lateral position were performed in two patients with severe thoracolumbar kyphosis combined with hip flexion contracture, which was not suitable for operation in the prone position. Case 1: a 33-year-old female AS patient still had severe hip flexion contracture due to poor rehabilitation after total hip replacement (THR). The range of movement of the hip was only about 15° in right and 10° in left. Pre-operativethoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), and sagittal vertical axis (SVA) were 52.4°, 49.1°, 42.7°, and 315 mm, respectively. Pedicle subtraction osteotomy (PSO) at L3 was performed in the lateral position. The eggshell procedure was used during osteotomy. Case 2: a 45-year-old male AS patient presented coexisting rigid thoracolumbar kyphosis and hip flexion contracture. The range of movement of the hip was only about 20° in right and 25° in left. Pre-operativeTK, TLK, LL and SVA were 34.9°, 66.8°, 58.8° and 290.8 mm, respectively. PSO at L2 was performed in lateral position. The eggshell procedure was also used. RESULTS: Sagittal malalignments of both patients were greatly improved. For case 1, the total operation time was 5.5 h. The blood loss was 1500 mL and the amount of allogeneic blood transfusion was 1580 mL during the operation. SVA was reduced to 127 mm and LL decreased from preoperative 42.7° to -28.4°. The correction angle through L3 was 34.7° and the correction angle through the osteotomy segment was 62.9°. For case 2, the duration of surgery was 6.5 h. The operative blood loss was 2000 mL and the total amount of blood transfusion was 2020 mL. SVA was reduced to 209.8 mm and LL decreased from preoperative 58.8° to 9.2°.The correction angle through L2 was 37.1° and the correction angle through the osteotomy segment was 55°. No intra-operative or post-operative complications were observed. Six months after PSO, case 1 had good posture for standing and sitting. The case 2 underwent bilateral THRs nine months after PSO. CONCLUSION: PSO could be performed in the lateral position successfully. For AS patients who cannot be placed in the prone position due to coexisting severe thoracolumbar kyphosis and hip flexion contracture, performing spinal osteotomy in the lateral position as the first step is an alternative.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34777531

RESUMO

Background: Recently, the brain-computer interface (BCI) has seen rapid development, which may promote the recovery of motor function in chronic stroke patients. Methods: Twelve stroke patients with severe upper limb and hand motor impairment were enrolled and randomly assigned into two groups: motor imagery (MI)-based BCI training with multimodal feedback (BCI group, n = 7) and classical motor imagery training (control group, n = 5). Motor function and electrophysiology were evaluated before and after the intervention. The Fugl-Meyer assessment-upper extremity (FMA-UE) is the primary outcome measure. Secondary outcome measures include an increase in wrist active extension or surface electromyography (the amplitude and cocontraction of extensor carpi radialis during movement), the action research arm test (ARAT), the motor status scale (MSS), and Barthel index (BI). Time-frequency analysis and power spectral analysis were used to reflect the electroencephalogram (EEG) change before and after the intervention. Results: Compared with the baseline, the FMA-UE score increased significantly in the BCI group (p = 0.006). MSS scores improved significantly in both groups, while ARAT did not improve significantly. In addition, before the intervention, all patients could not actively extend their wrists or just had muscle contractions. After the intervention, four patients regained the ability to extend their paretic wrists (two in each group). The amplitude and area under the curve of extensor carpi radialis improved to some extent, but there was no statistical significance between the groups. Conclusion: MI-based BCI combined with sensory and visual feedback might improve severe upper limb and hand impairment in chronic stroke patients, showing the potential for application in rehabilitation medicine.

6.
Cell Oncol (Dordr) ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34791638

RESUMO

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

7.
J Hepatocell Carcinoma ; 8: 1323-1338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765572

RESUMO

Background: Cytochrome P450 2C8 (CYP2C8) gene is one of the members of the cytochrome P450 enzymes (CYPs) gene family. The aim of this study was to reveal the function of CYP2C8 in hepatocellular carcinoma (HCC) and its effect on the sorafenib resistance. Methods: Differential expression analysis in multiple HCC datasets all suggested that CYP2C8 expression was significantly decreased in HCC tissues, compared with para-carcinoma liver tissues. The expression level of CYP2C8 was subsequently compared between HCC tissues and para-carcinoma liver tissues of 70 patients form Guangxi, China, with the result consistent with the above. Survival analysis and ROC analysis indicated that CYP2C8 was equipped with satisfactory diagnostic and prognostic value in HCC. To examine the effect of CYP2C8 on the malignant phenotype of HCC cells, stable transcriptional cell lines with CYP2C8 over-expression were established, and then Cell Counting Kit-8 (CCK8) assay, colony formation assay, cell cycle assay, cell invasion assay and wound healing assay were performed. Results: The results of aforementioned assays suggested that CYP2C8 over-expression restricted the proliferation, clonality, migration, invasion and cell cycle of HCC cells but had no significant effect on cell apoptosis. The enrichment analysis in terms of sequencing data of HCC cell lines with stable CYP2C8 over-expression suggested that CYP2C8 might be related to PI3K/Akt/p27Kip1 axis. The inhibition of CYP2C8 over-expression on PI3K/Akt/p27Kip1 axis was subsequently demonstrated with Western blot assay. In the rescue experiment, it was observed that both P27 inhibitor and PI3K agonist counteracted the repressed malignant phenotype caused by CYP2C8 over-expression, which further demonstrated that CYP2C8 played a role in HCC cells via PI3K/Akt/p27Kip1 axis. Discussion: The results demonstrated that CYP2C8 enhances the anticancer activity of sorafenib in vitro assays and in tumor xenograft model, with Ki-67 down-regulation and PI3K/Akt/p27Kip1 axis inhibition. In conclusion, these findings hinted that CYP2C8 restricted malignant phenotype and sorafenib resistance in HCC via PI3K/Akt/p27kip1 axis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34783165

RESUMO

Research on Flow Diverter (FD) has progressed over the past decades; however, the relationships between parameters such as stent diameter, porosity, and number of wires and the properties of FDs, such as partial compressive force and push resistance, are not well understood. In this study, the partial compressive force and push resistance of braided FDs with varying porosity (61%-75%), diameter (2.5-5.0 mm), and number of wires (48 or 64) were evaluated using Finite Element Analysis (FEA) and bench tests. At a small compression ratio, the 48-wire stents exhibited a larger partial compressive force than 64-wire stents of the same diameter. But when the compression ratio was 50%, the 64-wire stents had better resistance to pressure. The partial compressive force decreased as the stent diameter increased when all other parameters were equal. However, the influence of the diameter decreased as the stent porosity increased. The push resistance decreased as the porosity and diameter increased, and increased with the number of wires. These results provide useful information for FD design. Decreasing the number of wires can reduce the push resistance, while the push resistance is mainly influenced by the porosity and number of wires, and almost has no relationship with the partial compressive force. The FEA model proved very reliable, and corresponded well to the bench test results, which indicates that this model can be utilized to guide the design of FDs. This article is protected by copyright. All rights reserved.

9.
J Nanobiotechnology ; 19(1): 383, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809612

RESUMO

Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

10.
Adv Sci (Weinh) ; : e2102021, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716688

RESUMO

A high-throughput non-viral intracellular delivery platform is introduced for the transfection of large cargos with dosage-control. This platform, termed Acoustic-Electric Shear Orbiting Poration (AESOP), optimizes the delivery of intended cargo sizes with poration of the cell membranes via mechanical shear followed by the modulated expansion of these nanopores via electric field. Furthermore, AESOP utilizes acoustic microstreaming vortices wherein up to millions of cells are trapped and mixed uniformly with exogenous cargos, enabling the delivery of cargos into cells with targeted dosages. Intracellular delivery of a wide range of molecule sizes (<1 kDa to 2 MDa) with high efficiency (>90%), cell viability (>80%), and uniform dosages (<60% coefficient of variation (CV)) simultaneously into 1 million cells min-1 per single chip is demonstrated. AESOP is successfully applied to two gene editing applications that require the delivery of large plasmids: i) enhanced green fluorescent protein (eGFP) plasmid (6.1 kbp) transfection, and ii) clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated gene knockout using a 9.3 kbp plasmid DNA encoding Cas9 protein and single guide RNA (sgRNA). Compared to alternative platforms, this platform offers dosage-controlled intracellular delivery of large plasmids simultaneously to large populations of cells while maintaining cell viability at comparable delivery efficiencies.

11.
Mol Oncol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708506

RESUMO

The high-order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi-omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase-sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI-rich and CGI-poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional-level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer-related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity.

12.
ACS Omega ; 6(39): 25497-25505, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34632207

RESUMO

By implementing NMR, inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the UV-vis spectroscopic techniques, metabolites, mineral elements, and antioxidant activities (DPPH) of Peganum harmala L. samples from Manasi and Fuhai of Xinjiang were studied in this research to investigate the geographical environment impact at the molecular level. First of all, partial least squares discriminant analysis was conducted to explore differential endogenous metabolites. A total of 18 metabolites were identified, and 14 mineral element contents were calculated quantitatively, which displayed diverse changing trends from these two origins. Valine, succinic acid, betaine, sucrose, and vasicine exhibited significant differences between these two groups as well as mineral nutrient profiles (Mg, Cu, N, K, Na, P, Zn, C) and DPPH antioxidant activities (EC50). The obvious different characteristics of chemical components and antioxidant activities in these two groups were further verified by heat map cluster analysis. Pearson correlation analysis also revealed the remarkable relationship of chemical components and antioxidant activities, which are strongly associated with the regional environment. This study showed that the combination of methodologies proposed will be highly useful in evaluating the environmental variation and diversity in terrestrial ecosystems.

13.
JACS Au ; 1(9): 1459-1470, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34604855

RESUMO

The suppression of methane and coke formation over Ni-based catalysts for low temperature ethanol steam reforming remains challenging. This paper describes the structural evolution of Fe-modified Ni/MgAl2O4 catalysts and the influence of iron species on methane and coke suppression for low temperature ethanol steam reforming. Ni-Fe alloy catalysts are gradually oxidized by water to generate Ni-rich alloy and γ-Fe2O3 species at steam-to-carbon ratio of 4. The electron transfer from iron to nickel within Ni-Fe alloy weakens the CO adsorption and effectively alleviates the CO/CO2 methanation. The oxidation capacity of γ-Fe2O3 species promotes the transformation of ethoxy to acetate groups to avoid methane formation and the elimination of carbon deposits for anticoking. Ni10Fe10/MgAl2O4 shows a superior performance with a highest H2 yield of 4.6 mol/mol ethanol at 400 °C for 15 h. This research could potentially provide instructions for the design of Ni-based catalysts for low-temperature ethanol steam reforming.

14.
Phys Chem Chem Phys ; 23(33): 18221-18226, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34612285

RESUMO

In general, hydrostatic pressure can suppress electrical polarization, instead of creating and/or enhancing polarization like strain engineering. Here, a combination of first-principles calculations and CALYPSO crystal structures prediction is used to point out that hydrostatic pressure applied on antiperovskite MgCNi3 can stabilize polarization with metallicity, and thus a polar metal can exist under high pressure. Strikingly, the metallic polar phase of MgCNi3 exhibits an original linear-cubic coupling between polar and nonpolar modes, resulting in an asymmetrical double-well when the polarization is switched. Moreover, another novel phase of MgCNi3 under high pressure possesses an enhanced hardness stemming from a robust s-s electrons interaction of an unexpected C-C bond, rather than typical sp3 orbital hybridization. These discoveries open new routes to design superhard materials and polar metals.

15.
Nat Commun ; 12(1): 5733, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593794

RESUMO

In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe3+) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Exossomos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/uso terapêutico , Linhagem Celular Tumoral/transplante , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Exossomos/imunologia , Exossomos/metabolismo , Feminino , Ferroptose/imunologia , Humanos , Ácido Hialurônico/química , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
16.
Chem Commun (Camb) ; 57(87): 11473-11476, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34652356

RESUMO

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we technically developed the metal-polyphenolic nanosystem with precise NIR-II fluorescence-imaging guidance for combining hafnium (Hf)-sensitized radiotherapy with PTT to regress tumor growth.

17.
ACS Nano ; 15(10): 16934-16945, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34661387

RESUMO

Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.


Assuntos
Microambiente Tumoral , Terapia por Ultrassom , Linhagem Celular Tumoral , Ácido Láctico , Espécies Reativas de Oxigênio , Hipóxia Tumoral
18.
Cells ; 10(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34685501

RESUMO

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.

19.
Orthop Surg ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708550

RESUMO

OBJECTIVES: To investigate whether the immediate thoracic kyphosis (TK) and acetabular anteversion (AA) postoperatively are correlated with proximal junctional failure (PJF) in adult spinal deformity (ASD) patients underwent surgical treatment. METHODS: This is a retrospective study. Following institutional ethics approval, a total of 57 patients (49 Female, eight Male) with ASD underwent surgery fused to sacroiliac bone (S1, S2, or ilium) from March 2014 to January 2019 were included. All of those patients were followed up for at least 2 years. Demographic, radiographic and surgical data were recorded. The maximum range of flexion motion (F-ROM) and extension motion (E-ROM) actively of hip joints was measured and recorded at pre- and postoperation. The sum of F-ROM and E-ROM was defined as the range of hip motion (H-ROM). Receiver operating characteristic (ROC) curve analysis was used to obtain the cut off value of parameters for PJF. A Kaplan-Meier curve and log-rank test were used to analyze the differences in PJF-free survival. RESULTS: In all, 14 patients developed PJF during follow-up. Comparisons between patients with and without PJF showed significant differences in immediate TK (P < 0.001) and AA (P = 0.027) postoperatively. ROC curve analysis determined an optimal threshold of 13° for immediate AA postoperatively (sensitivity = 74.3%, specificity = 85.7%, area under the ROC curve [AUC] = 0.806, 95% CI [0.686-0.926]). Nineteen patients with post-AA ≤13° were assigned into the observational group, and 38 patients with post-AA >13° were being as the control group. Patients in the observational group had smaller H-ROM (P = 0.016) and F-ROM (P < 0.001), but much larger E-ROM (P < 0.001). There were 10 patients showing PJF in the observational group and four in the control group (10/9 vs 4/34, P < 0.001). PJF-free survival time significantly decreased in the observational group (P = 0.001, log-rank test). Furthermore, patients in the observational group had much larger TK (post-TK, P = 0.015). The optimal threshold for post-TK (sensitivity = 85.7%, specificity = 76.7%; AUC = 0.823, 95% CI [0.672-0.974]) was 28.1° after the ROC curve was analyzed. In the observational group, those patients with post-TK ≥28.1° had significantly higher incidence of PJF (9/2 vs 1/7, P < 0.001) than those with post-TK < 28.1°. Moreover, PJF-free survival time in those patients significantly decreased (P = 0.001, log-rank test). CONCLUSIONS: ASD patients with acetabular anteversion of ≤13° at early postoperation may suffer significantly restricted hip motion and much higher incidence of PJF during follow-up, moreover, in those patients, postoperative TK ≥28.1° would be a significant risk factor for PJF developing.

20.
World J Clin Cases ; 9(27): 8242-8248, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34621887

RESUMO

BACKGROUND: One of the most common complications following surgery for midshaft clavicle fracture is nonunion/delayed union. Extracorporeal shock wave therapy (ESWT) is an alternative to promote new bone formation without surgical complications. To date, no literature has reported low-intensity ESWT (LI-ESWT) in delayed union of midshaft clavicle fracture. CASE SUMMARY: We reported a 66-year-old Chinese amateur cyclist with clavicle delayed union treated with 10 sessions of LI-ESWT (radial, 0.057 mJ/mm2, 3 Hz, 3000 shocks). No anesthetics were applied, and no side effects occurred. At the 4 mo and 7 mo follow-ups, the patient achieved clinical and radiographical recovery, respectively. CONCLUSION: In conclusion, our findings indicated that LI-ESWT could be a good option for treating midshaft clavicular delayed union.

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