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1.
Biochem Biophys Res Commun ; 541: 95-101, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33493685

RESUMO

The tumor microenvironment is a complex microenvironment that combines the biochemical and biophysical factors. When the cells are exposed to the microenvironment, the direct biophysical factor is the matrix hardness. As an auxiliary indicator of clinical disease diagnosis, it is still not clear how the matrix hardness induces cell malignant changes and the regulation mechanisms. In this study, we identified that hard matrix significantly promoted cancer cell migratory behaviors. Cell shape was closely associated with cancer cell malignancy, the high malignant cells were associated with high ratios of length/width and low circularity. F-actin networks were also linked with extracellular matrix, it was not regularly distributed when cells were in non-malignant tumor phases or under F-actin inhibition. F-actin might play the key role that transmitted the signal from extracellular matrix to the intracellular organelles. Further study confirmed that active YAP was translocated to nucleus on hard matrix. Cells on hard matrix with cytochalasin D reversed the cancer cell malignancy, meanwhile F-actin re-distributed to the membrane and YAP nucleus translocations were hindered. This work confirmed that F-actin and YAP were upstream-downstream cascade for the cellular and nucleus outside-in signal transductions. The above results demonstrated that hard matrix promoted breast cancer cell malignant behaviors through F-actin network and YAP activation. These results not only described the signal transductions from extracellular to intracellular that was initiated by the biophysical tumor microenvironment, but provided clinical intervention ideas for cancer treatments.

2.
Biomed Res Int ; 2021: 6611244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506022

RESUMO

Liquid biopsy is conducted through minimally invasive or noninvasive procedures, and the resulting material can be subjected to genomic, proteomic, and lipidomic analyses for early diagnosis of cancers and other diseases. Extracellular vesicles (EVs), one kind of promising tool for liquid biopsy, are nanosized bilayer particles that are secreted by all kinds of cells and that carry cargoes such as lipids, proteins, and nucleic acids, protecting them from enzymatic degradation in the extracellular environment. In this review, we provide a comprehensive introduction to the properties and applications of EVs, including their biogenesis, contents, sample collection, isolation, and applications in diagnostics based on liquid biopsy.

3.
Cell Signal ; : 109877, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33296740

RESUMO

Tooth and bone are independent tissues with a close relationship. Both are composed of a highly calcified outer structure and soft inner tissue, and both are constantly under mechanical stress. In particular, the alveolar bone and tooth constitute an occlusion system and suffer from masticatory and occlusal force. Thus, mechanotransduction is a key process in many developmental, physiological and pathological processes in tooth and bone. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important participants in mechanotransduction, but their functions in tooth and bone are poorly understood. This review summarizes our current understanding of mechanosensitive ion channels and their roles in tooth and bone tissues. Research in these areas may shed new light on the regulation of tooth and bone tissues and potential treatments for diseases affecting these tissues.

4.
PeerJ ; 8: e10062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194377

RESUMO

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in head and neck cancer, with high recurrence and mortality. Early diagnosis and efficient therapeutic strategies are vital for the treatment of OSCC patients. Exosomes can be isolated from a broad range of different cell types, implicating them as important factors in the regulation of human physiological and pathological processes. Due to their abundant cargo including proteins, lipids, and nucleic acids, exosomes have played a valuable diagnostic and therapeutic role across multiple diseases, including cancer. In this review, we summarize recent findings concerning the content within and participation of exosomes relating to OSCC and their roles in tumorigenesis, proliferation, migration, invasion, metastasis, and chemoresistance. We conclude this review by looking ahead to their potential utility in providing new methods for treating OSCC to inspire further research in this field.

5.
BMC Oral Health ; 20(1): 321, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176777

RESUMO

BACKGROUND: Based on low-dose radiation Cone-bean computed tomography (CBCT) images, This study aims to establish a space coordinate system, which offers more precise and comparable evaluation on changes of maxillary third molars influenced by orthodontic treatment with premolar extraction in adults. The system suggests promising application prospect in future studies related to CBCT superimposition and evaluation for its feasibility and efficiency. METHODS: Forty-nine maxillary third molars from 27 patients (mean age, 20.78 years) were included. CBCT images were obtained before and after orthodontic treatment with premolars extracted (mean treatment duration, 31.47 months). The changes in the position, angulation, and rotation of the third molars were evaluated with a space coordinate system using four landmarks: anterior nasal spine (ANS), posterior nasal spine (PNS), left and right orbitales. RESULTS: After orthodontic treatment, the third molars moved forward (adjusted mean, 1.44 mm) (p < 0.001) and downward (adjusted mean, 2.87 mm) (p < 0.001) accompanied by outward rotation of the crowns (adjusted mean, 5.38°) (p = 0.001), while changes in angulation were insignificant. CONCLUSIONS: This was the first study to systematically investigate the spatial position change of maxillary third molars in adult patients who received orthodontic treatment with premolar extraction. During the process, maxillary third molars moved downward and forward accompanied by outward rotation of the crowns. Orthodontists should take tooth movement potential into consideration when making extraction plans.

6.
Cancer Manag Res ; 12: 9679-9689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116827

RESUMO

Introduction: Clinical studies have indicated a relationship between diabetic nephropathy (DN) and the incidence and prevalence of renal cell carcinoma (RCC). However, the mechanism linking diabetic nephropathy and renal cell carcinoma has not yet to be identified. Methods: In this study, a total of 42 male Sprague Dawley (SD) rats were randomly assigned to a DN group (n=35) and a control group (n=7). All animals in the DN group were unilaterally nephrectomized and treated with streptozotocin with the development of blood glucose levels >16.7mmol/L and dominant proteinuria and were compared to controls without such changes. Histopathologic alterations in the kidneys were examined by HE staining and Ki-67 immunohistochemistry. Differentially expressed genes were identified and validated by RNA-seq and PCR. Results: As the results, except for two rats that failed to develop the DN model and were excluded from the analysis, 33 rats in the DN group with overt signs of DN demonstrated significantly higher food and water intake, urine production, and urine protein and urinary protein/creatinine ratio than controls. Overall, 15.2% (n=5/33) of DN animals developed RCC while none tumors were observed in the control group (n=0/7). RNA-seq analysis in these animals indicated different TRPV5 gene expression and calcium pathway expression in DN animals with developing tumors, when compared with animals with no obvious tumors. In addition, DN animals diagnosed with RCC showed increased expression of GLUT2 and c-met, when compared to controls and DN animals without tumors. Discussion: In conclusion, the disordered calcium metabolism, especially disturbed TRPV5 mediated Ca2+ signal, may have been related to the development of RCC in DN rats. Further studies related to the detailed mechanism are still needed.

8.
Front Immunol ; 11: 1843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922398

RESUMO

The therapeutic potential of mesenchymal stem cells (MSCs) has been investigated in many preclinical and clinical studies. This potential is dominantly based on the immunosuppressive properties of MSCs. Although the therapeutic profiles of MSC transplantation are still not fully characterized, accumulating evidence has revealed that B cells change after MSC infusion, in particular inducing regulatory B cells (Bregs). The immunosuppressive effects of Bregs have been demonstrated, and these cells are being evaluated as new targets for the treatment of inflammatory diseases. MSCs are capable of educating B cells and inducing regulatory B cell production via cell-to-cell contact, soluble factors, and extracellular vesicles (EVs). These cells thus have the potential to complement each other's immunomodulatory functions, and a combined approach may enable synergistic effects for the treatment of immunological diseases. However, compared with investigations regarding other immune cells, investigations into how MSCs specifically regulate Bregs have been superficial and insufficient. In this review, we discuss the current findings related to the immunomodulatory effects of MSCs on regulatory B cells and provide optimal strategies for applications in immune-related disease treatments.

9.
Exp Neurol ; 334: 113461, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32926860

RESUMO

We investigated whether type 2 diabetes mellitus (T2DM), a risk factor of stroke, affects the level of scavenger receptor CD36 and the uptake of its ligand, oxidized LDL (oxLDL); and whether pioglitazone, a drug that enhances CD36, promotes oxLDL uptake. Compared to normoglycemic db/+ mice, adult db/db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood, brain, and bone marrow as detected by flow cytometry, which correlated with elevated plasma soluble-CD36 as determined by ELISA. Increased CD36 expression was found in brain macrophages and microglia of both genotypes 7 days after ischemic stroke. In juvenile db/db mice, prior to obesity and hyperglycemia, only a mild reduction of surface CD36 was found in blood neutrophils, while all other myeloid cells showed no difference relative to the db/+ strain. In vivo, oral pioglitazone treatment for four weeks increased CD36 levels on myeloid cells in db/db mice. In vitro, uptake of oxLDL by bone marrow derived macrophages (BMDMs) of db/db mice was reduced relative to db/+ mice in normal glucose medium. OxLDL uptake inversely correlated with glucose levels in the medium in db/+ BMDMs. Furthermore, pioglitazone restored oxLDL uptake by BMDMs from db/db mice cultured in high glucose. Our data suggest that T2DM is associated with reduced CD36 on adult myeloid cells, and pioglitazone enhances CD36 expression in db/db cells. T2DM or high glucose reduces oxLDL uptake while pioglitazone enhances oxLDL uptake. Our findings provide new insight into the mechanism by which pioglitazone may be beneficial in the treatment of insulin resistance.

10.
Int J Biol Macromol ; 163: 1208-1222, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32645496

RESUMO

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.

11.
J Cereb Blood Flow Metab ; 40(11): 2165-2178, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32669022

RESUMO

The leptomeningeal collateral status is an independent predictor of stroke outcome. By means of optical coherent tomography angiography to compare two mouse strains with different extent of native leptomeningeal collateralization, we determined the spatiotemporal dynamics of collateral flow and downstream hemodynamics following ischemic stroke. A robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, with continued expansion over the course of seven days. In contrast, little collateral recruitment was seen in Balb/C mice during- and one day after MCAO, which coincided with a greater infarct size and worse functional outcome compared to C57BL/6, despite a slight improvement of cortical perfusion seven days after MCAO. Both strains of mice experienced a reduction of blood flow in the penetrating arterioles (PA) by more than 90% 30-min after dMCAO, although the decrease of PA flow was greater and the recovery was less in the Balb/C mice. Further, Balb/C mice also displayed a prolonged greater heterogeneity of capillary transit time after dMCAO in the MCA territory compared to C57BL/6 mice. Our data suggest that the extent of native leptomeningeal collaterals affects downstream hemodynamics with a long lasting impact in the microvascular bed after cortical stroke.

13.
Stem Cells Dev ; 29(16): 1073-1083, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32552417

RESUMO

Mesenchymal stromal cells (MSCs) have become a promising treatment for inflammation-related diseases, and their therapeutic efficacy mainly depends on crosstalk between MSCs and inflammation. However, methods to improve the immunosuppressive efficiency of MSCs in different diseases still need to be developed. In this study, we investigated whether preconditioning MSCs with a disease-related inflammatory cytokine could increase their immunosuppressive properties and improve therapeutic efficacy. In a contact hypersensitivity (CHS) mouse model, inflammatory profile screening revealed that among all tested cytokines, monocyte chemotactic protein-1 (MCP-1) exhibited the most significantly increased level in the local microenvironment. As expected, MSCs preconditioned with MCP-1 (P-MSCs) exhibited an enhanced ability to downregulate proinflammatory cytokine secretion, induce regulatory T cells, inhibit T cell proliferation, and polarize M2-type macrophages. In vivo experiments showed that P-MSCs alleviated ear swelling and local proinflammatory cytokine production more effectively than control MSCs. Mechanistically, MCP-1 could significantly activate the signal transducer and activator of transcription 3 (STAT3) signaling pathway and induce the expression of cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) in MSCs. STAT3 inhibitor reversed the MCP-1-mediated enhancing of their immunosuppressive ability. Collectively, our findings demonstrate that CHS-related MCP-1 preconditioning enhanced the immunomodulatory effects of MSCs and improved their therapeutic efficacy in CHS. Enhancing the immunosuppressive efficacy of MSCs by preconditioning with certain disease-related inflammatory cytokines may provide a new strategy for MSC-based therapies for inflammatory diseases.

14.
Food Sci Nutr ; 8(5): 2436-2444, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32405400

RESUMO

Chicken soup is one of the most popular Chinese-style soups due to its high nutritional value and special flavor. However, the nutrients, mainly soluble protein, in the soup are relatively low. The aim of the present work was to enhance the protein solubility and other physicochemical properties of Cordyceps militaris chicken soup by enzymatic hydrolysis pretreatment. Results indicated that the soluble protein dissolution rate and flavor nucleotides (I+G) of Cordyceps militaris chicken soup had 1.6-fold and 0.5-fold increase, respectively, after enzymatic hydrolysis pretreatment. Not only the contents of total amino acids (TAA) and essential amino acids (EAA) in Cordyceps militaris chicken soup significantly increased, the organoleptic quality was also markedly improved after the enzymatic hydrolysis pretreatment. The present work provides a potential approach, which is enzymatic hydrolysis pretreatment of chicken meat, to enhance the protein solubility and physicochemical quality of Cordyceps militaris chicken soup.

16.
iScience ; 23(3): 100919, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32114378

RESUMO

Lithium selenium (Li-Se) batteries have attracted increasing interest for its high theoretical volumetric capacities up to 3,253 Ah L-1. However, current studies are largely limited to electrodes with rather low mass loading and low areal capacity, resulting in low volumetric performance. Herein, we report a design of covalent selenium embedded in hierarchical nitrogen-doped carbon nanofibers (CSe@HNCNFs) for ultra-high areal capacity Li-Se batteries. The CSe@HNCNFs provide excellent ion and electron transport performance, whereas effectively retard polyselenides diffusion during cycling. We show that the Li-Se battery with mass loading of 1.87 mg cm-2 displays a specific capacity of 762 mAh g-1 after 2,500 cycles, with almost no capacity fading. Furthermore, by increasing the mass loading to 37.31 mg cm-2, ultra-high areal capacities of 7.30 mAh cm-2 is achieved, which greatly exceeds those reported previously for Li-Se batteries.

17.
Cell Prolif ; 53(3): e12780, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32031738

RESUMO

OBJECTIVES: RING finger protein 8 (RNF8) is an E3 ligase that plays an essential role in DSB repair. p53 is a well-established tumour suppressor and cellular gatekeeper of genome stability. This study aimed at investigating the functional correlations between RNF8 and p53 in DSB damage repair. MATERIALS AND METHODS: In this article, wild-type, knockout and shRNA-depleted HCT116 and U2OS cells were stressed, and the roles of RNF8 and p53 were examined. RT-PCR and Western blot were utilized to investigate the expression of related genes in damaged cells. Cell proliferation, apoptosis and neutral cell comet assays were applied to determine the effects of DSB damage on differently treated cells. DR-GFP, EJ5-GFP and LacI-LacO targeting systems, flow cytometry, mass spectrometry, IP, IF, GST pull-down assay were used to explore the molecular mechanism of RNF8 and p53 in DSB damage repair. RESULTS: We found that RNF8 knockdown increased cellular sensitivity to DSB damage and decreased cell proliferation, which was correlated with high expression of the p53 gene. RNF8 improved the efficiency of DSB repair by inhibiting the pro-apoptotic function of p53. We also found that RNF8 restrains cell apoptosis by inhibiting over-activation of ATM and subsequently reducing p53 acetylation at K120 through regulating Tip60. CONCLUSIONS: Taken together, these findings suggested that RNF8 promotes efficient DSB repair by inhibiting the pro-apoptotic activity of p53 through regulating the function of Tip60.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Lisina Acetiltransferase 5/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Apoptose , Linhagem Celular Tumoral , Células HCT116 , Humanos
18.
Am J Pathol ; 190(3): 642-659, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31972158

RESUMO

Ischemia due to hypoperfusion is one of the most common forms of acute kidney injury. We hypothesized that kidney hypoxia initiates the up-regulation of miR-218 expression in endothelial progenitor cells (EPCs) to guide endocapillary repair. Murine renal artery-derived EPCs (CD34+/CD105-) showed down-regulation of mmu-Mir218-5p/U6 RNA ratio after ischemic injury, while in human renal arteries, MIR218-5p expression was up-regulated after ischemic injury. MIR218 expression was clarified in cell culture experiments in which increases in both SLIT3 and MIR218-2-5p expressions were observed after 5 minutes of hypoxia. ROBO1 transcript, a downstream target of MIR218-2-5p, showed inverse expression to MIR218-2-5p. EPCs transfected with a MIR218-5p inhibitor in three-dimensional normoxic culture showed premature capillary formation. Organized progenitor cell movement was reconstituted when cells were co-transfected with Dicer siRNA and low-dose Mir218-5p mimic. A Mir218-2 knockout was generated to assess the significance of miR-218-2 in a mammalian model. Mir218-2-5p expression was decreased in Mir218-2-/- embryos at E16.5. Mir218-2-/- decreased CD34+ angioblasts in the ureteric bud at E16.5 and were nonviable. Mir218-2+/- decreased peritubular capillary density at postnatal day 14 and increased serum creatinine after ischemia in adult mice. Systemic injection of miR-218-5p decreased serum creatinine after injury. These experiments demonstrate that miR-218 expression can be triggered by hypoxia and modulates EPC migration in the kidney.


Assuntos
Lesão Renal Aguda/patologia , Isquemia/patologia , MicroRNAs/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Idoso , Animais , RNA Helicases DEAD-box , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Feminino , Humanos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microvasos/patologia , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Receptores Imunológicos/genética , Ribonuclease III
19.
J Cereb Blood Flow Metab ; 40(9): 1778-1796, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31558106

RESUMO

The functional consequences of ischemic stroke in the remote brain regions are not well characterized. The current study sought to determine changes in hippocampal oscillatory activity that may underlie the cognitive impairment observed following distal middle cerebral artery occlusion (dMCAO) without causing hippocampal structural damage. Local field potentials were recorded from the dorsal hippocampus and cortex in urethane-anesthetized rats with multichannel silicon probes during dMCAO and reperfusion, or mild ischemia induced by bilateral common carotid artery occlusion (CCAO). Bilateral change of brain state was evidenced by reduced theta/delta amplitude ratio and shortened high theta duration following acute dMCAO but not CCAO. An aberrant increase in the occurrence of sharp-wave-associated ripples (150-250 Hz), crucial for memory consolidation, was only detected after dMCAO reperfusion, coinciding with an increased occurrence of high-frequency discharges (250-450 Hz). dMCAO also significantly affected the modulation of gamma amplitude in the cortex coupled to hippocampal theta phase, although both hippocampal theta and gamma power were temporarily decreased during dMCAO. Our results suggest that MCAO may disrupt the balance between excitatory and inhibitory circuits in the hippocampus and alter the function of cortico-hippocampal network, providing a novel insight in how cortical stroke affects function in remote brain regions.

20.
Nanotechnology ; 31(1): 015402, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31514178

RESUMO

Germanium (Ge) has gained a great deal of attention as an anode material for sodium ion batteries (SIBs) and lithium ion batteries (LIBs) for its high theoretical capacity and ion diffusivity. Unfortunately, Ge particle pulverization triggered by huge volume expansion during the alloying and dealloying processes can cause rapid capacity fade. Herein we report a facile method for the preparation of ultrafine Ge nanoparticles embedded in hierarchical N-doped multichannel carbon fibers (denoted as Ge-NMCFs) by electrospinning. The hierarchical carbon matrix not only provides sufficient internal void space to accommodate the large volume expansion of Ge nanoparticles, but also provides numerous open channels for the easy access of electrolyte and Na/Li ions. As half-cell tests revealed, the composite provides discharge capacity of 303 mA h g-1 (1st cycle) and 160 mA h g-1 (700th cycle) for SIBs, 1146.7 mA h g-1 (1st cycle) and 600 mA h g-1 (500th cycle) for LIBs at a current density of 500 mA g-1 (all the presented capacity based on the total weight of Ge/C composites). Density functional theory calculation suggests that N-doped in carbon can enhance the Na/Li ion storage and improve the electrochemical performance. This demonstration is an important step towards the development of SIBs and LIBs with much higher specific energy capacity and longer cycle stability.

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