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1.
Br J Cancer ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33828254

RESUMEN

BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC. METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively. CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS. GOV IDENTIFIER: NCT03332498.

2.
J Cell Mol Med ; 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33830648

RESUMEN

Our previous studies have shown that the Adipose-derived mesenchymal stem cells (ADSCs) can regulate metastasis and development of ovarian cancer. However, its specific mechanism has yet to be fully revealed. In this study, an RNA-seq approach was adopted to compare the differences in mRNA levels in ovarian cancer cells being given or not given ADSCs. The mRNA level of paired box 8 (PAX8) changed significantly and was confirmed as an important factor in tumour-inducing effect of ADSCs. In comparison with the ovarian cancer cells cultured in the common growth medium, those cultured in the medium supplemented with ADSCs showed a significant increase of the PAX8 level. Moreover, the cancer cell growth could be restricted, even in the ADSC-treated group (P < .05), by inhibiting PAX8. In addition, an overexpression of PAX8 could elevate the proliferation of ovarian cancer cells. Moreover, Co-IP assays in ovarian cancer cells revealed that an interaction existed between endogenous PAX8 and TAZ. And the PAX8 levels regulated the degradation of TAZ. The bioluminescence images captured in vivo manifested that the proliferation and the PAX8 expression level in ovarian cancers increased in the ADMSC-treated group, and the effect of ADSCs in promoting tumours was weakened through inhibiting PAX8. Our findings indicate that the PAX8 expression increment could contribute a role in promoting the ADSC-induced ovarian cancer cell proliferation through TAZ stability regulation.

3.
Orthop Surg ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33821565

RESUMEN

OBJECTIVE: To evaluate mid- to long-term results of revision total hip arthroplasty for massive femoral bone loss using a cementless modular, fluted, tapered stem. METHODS: This is a retrospective study performed at a single hospital. During the period of January 2007 to January 2015, 33 patients (34 hips) underwent primary revision surgery with cementless modular, fluted, tapered stems due to femoral bone loss. Sixteen men and 17 women were included in the study, with an average age of 63.9 ± 11.7 years (range, 27 to 88 years). Operative data including operative duration, length of incision, drainage volume and duration, blood loss and transfusion, cases of bone graft and extended trochanteric osteotomy were recorded. Clinical evaluation was performed using Harris hip score (HHS), visual analogue scale (VAS), and patients' satisfaction. Radiographic data including femoral stem fixation, subsidence, integrin of allograft bone, and leg length discrepancy were assessed. Complications and survivorship were evaluated using Kaplan-Meier survival rate. RESULTS: The mean follow-up was 9.1 ± 2.5 years (range, 5-13 years). The Harris hip score was 43.6 ± 11.5 preoperatively and maintained at 86.5 ± 6.6 at the time of latest follow-up (P < 0. 05). The X-ray showed bone ingrowth fixation in 30 hips (88%), fibrous stable fixation in three hips (9%), and instability in one hip (3%). The average stem subsidence was 3.9 ± 2.2 mm (range, 1 to 10 mm). The mean difference in leg length in our study was 3.3 ± 2.7 mm (range, 0 to 10 mm), and the leg length discrepancy in 28 (82%) patients was within 5 mm. No case of junction fracture was observed. Seven (21%) intraoperative fractures occurred in our study. Three (9%) cases with infection were observed after revision. Six (18%) patients had lower limb vein thrombosis. The survivorship of prostheses with re-revision for any reason was 95% (95% CI, 12.0 to 13.0) at the 10-year follow-up. Three (9%) re-revisions were needed, including one for aseptic loosening, one for dislocation, and one for infection. CONCLUSION: The mid- to long-term results of revision total hip arthroplasty with the cementless modular, fluted, tapered stems are encouraging for massive femoral bone loss.

4.
J Pers Med ; 11(3)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33803960

RESUMEN

3GO is a condition in which hypertension, hyperglycemia, and dyslipidemia co-occur, and these conditions are related to each other and genetic and environmental factors. We hypothesized that common genetic variants and their interactions with lifestyles influenced 3GO risk. We aimed to explore common genetic variants to affect 3GO risk and their haplotype interaction with lifestyles in a city hospital-based cohort in 58,701 Koreans > 40 years. 3GO was defined as SBP ≥ 140 mmHg and DBP ≥ 90 mmHg for hypertension, fasting blood glucose ≥ 126 mg/dL for hyperglycemia, and LDL ≥ 160 mg/dL or HDL ≤ 40 mg/dL, or triglyceride ≥ 200 mg/dL for dyslipidemia. Haplotypes were generated by genetic variants selected from genome-wide association study ((GWAS) an observational study of the genetic variation of the whole genome in different individuals, used to see if any variation is related to traits) after adjusting for age, sex, area of residence, and body mass index (BMI). Nutrient intakes were assessed using food frequency questionnaires. Interactions between haplotype and lifestyles and 3GO risk were investigated. Parameters related to metabolic syndrome were significantly different in the 0GO, 1-2GO, and 3GO groups, that is, groups of individuals with none, one to two, or all three of the components of 3GO. At the 11q23 locus, KCNQ1_rs2237892, ZPR1_rs2075291, APOA5_rs662799, APOA1_rs5072, and SIK3_rs151139277, influenced 3GO risk, and the minor alleles of their haplotype had a 3GO risk 3.23 times higher than the major alleles. For subjects with a high energy intake, the 3GO risk of the minor alleles was significantly higher than that of the major alleles (OR = 3.230, 95% confidence interval (CI) = 2.062~5.061, p < 0.001). BMI, HbA1c, SBP, and serum concentrations of glucose, HDL, and triglyceride were significantly higher for the minor allele than the major alleles (p < 0.001). The haplotype interacted with the intakes of protein (p = 0.033), digestible carbohydrate (p = 0.012), fat (p = 0.008), and undigestible carbohydrates (p = 0.015) to increase 3GO risk. An interaction was also observed between smoking and the haplotype (p = 0.007). The minor allele effects on 3GO incidence were higher in the high digestible carbohydrate intake and smoking groups. By contrast, the minor allele impacts on 3GO frequencies were much higher in the low intake of undigestible carbohydrates, protein, and fat. In conclusion, people who carry a minor allele of the 11q23 locus haplotype should avoid smoking and replace digestible carbohydrate intake with consuming high-quality protein, healthy fat, and undigestible carbohydrates.

5.
Bioresour Technol ; 332: 125109, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33839508

RESUMEN

Anaerobic digestion (AD) systems with high substrate concentrations are characterized by high viscosity, which affects material and energy transfer efficiencies, thereby influencing methane production efficiency. In this study, adding granular activated carbon (GAC) and increasing the temperature decreased the viscosity by 4.56-10.19% and 27.13-28.85%, respectively, and improved AD efficiency. Adding GAC and increasing the temperature enhanced the methane yields by 34.37-38.15% and 25.60-28.31%, respectively. Distance-based redundancy analysis showed that the viscosity, temperature, and GAC had the greatest effects on the composition of the microbial community. The dominant bacteria in the medium-temperature AD system at the phylum level belonged to Firmicutes, Bacteroidetes, and Euryarchaeota. In addition to the dominant bacteria in the medium-temperature AD system, the thermophilic phylum Thermotogae was abundant in the high-temperature AD system. Moreover, the relative abundance of Euryarchaeota, which contained most of the methanogens, was higher in the high-temperature AD system than in the medium-temperature AD system.

6.
J Orthop Surg Res ; 16(1): 261, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33853660

RESUMEN

BACKGROUND: Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter. METHODS: For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized. RESULTS: At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks. CONCLUSIONS: This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions.

7.
Oncol Rep ; 45(6)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33846801

RESUMEN

Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma characterized by high aggressiveness and extremely poor patient prognosis. The germ cell­specific gene 2 protein (GSG2) is a histone H3 threonine­3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in the progression and development of CCA remain elusive. In the present study, the association between GSG2 and CCA was elucidated. Firstly, we demonstrated that GSG2 was overexpressed in CCA specimens and HCCC­9810 and QBC939 cells by immunohistochemical (IHC) staining. It was further revealed that high expression of GSG2 in CCA had significant clinical significance in predicting disease deterioration. Subsequently, cell proliferation, apoptosis, cell cycle distribution and migration were measured by MTT, flow cytometry, and wound healing assays, respectively in vitro. The results demonstrated that downregulation of GSG2 decreased proliferation, promoted apoptosis, arrested the cell cycle and weakened migration in the G2 phase of CCA cells. Additionally, GSG2 knockdown inhibited CCA cell migration by suppressing epithelial­mesenchymal transition (EMT)­related proteins, such as N­cadherin and vimentin. Mechanistically, GSG2 exerted effects on CCA cells by modulating the PI3K/Akt, CCND1/CDK6 and MAPK9 signaling pathways. In vivo experiments further demonstrated that GSG2 knockdown suppressed tumor growth. In summary, GSG2 was involved in the progression of CCA, suggesting that GSG2 may be a potential therapeutic target for CCA patients.

8.
Plant Dis ; 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33858186

RESUMEN

Plum pox or Sharka disease, caused by infection with plum pox virus (PPV), results in enormous economic losses to the stone fruit industry. However, the frequency and distribution of PPV remains unclear in China, the world's largest stone fruit producer. Systemic visual surveys were performed on stone fruit trees in China from 2008 to 2018, and the results suggest that plum pox disease is widely distributed on common apricots (Prunus armeniaca) and Japanese apricots (P. mume), with an average symptoms incidence rate >30% in the latter. In samples collected from Beijing, Nanjing, Shanghai, Wuhan, Wuxi, and Yuncheng, PPV was detected in 77% (85 out of 110) of collected samples by immunochromatographic (IC) strip tests and RT-PCR, and 96% (67 out of 70) of samples showing Sharka symptoms were PPV-positive. Transmission electron microscopy revealed filamentous particles of ~640 × 12.5 nm (n = 19) in size, and pinwheel inclusions in symptomatic plants, but not in the asymptomatic and PPV negative plant. Full-length genomes were determined for four isolates (three from Japanese apricot and one from common apricot), and phylogenetic analyses indicated that all four isolates belong to a clade PPV-D, despite slight differences in genome size. These findings not only highlight the widespread occurrence and distribution of PPV in China, but also provide detailed information about the genomic characteristics and evolutionary position of PPV isolates in China.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33848246

RESUMEN

This article investigates spectral chromatic and spatial defocus aberration in a monocular hyperspectral image (HSI) and proposes methods on how these cues can be utilized for relative depth estimation. The main aim of this work is to develop a framework by exploring intrinsic and extrinsic reflectance properties in HSI that can be useful for depth estimation. Depth estimation from a monocular image is a challenging task. An additional level of difficulty is added due to low resolution and noises in hyperspectral data. Our contribution to handling depth estimation in HSI is threefold. Firstly, we propose that change in focus across band images of HSI due to chromatic aberration and band-wise defocus blur can be integrated for depth estimation. Novel methods are developed to estimate sparse depth maps based on different integration models. Secondly, by adopting manifold learning, an effective objective function is developed to combine all sparse depth maps into a final optimized sparse depth map. Lastly, a new dense depth map generation approach is proposed, which extrapolate sparse depth cues by using material-based properties on graph Laplacian. Experimental results show that our methods successfully exploit HSI properties to generate depth cues. We also compare our method with state-of-the-art RGB image-based approaches, which shows that our methods produce better sparse and dense depth maps than those from the benchmark methods.

10.
Plants (Basel) ; 10(3)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33801805

RESUMEN

In the present study, we utilized high throughput and Sanger sequencing to determine the complete nucleotide sequence of a putative new ilarvirus species infecting sweet cherry, tentatively named prunus virus I (PrVI). The genome of PrVI is comprised of three RNA segments of 3474 nt (RNA1), 2911 nt (RNA2), and 2231 nt (RNA3) and features conserved motifs representative of the genus Ilarvirus. BlastN analysis revealed 68.1-71.9% nt identity of PrVI with strawberry necrotic shock virus (SNSV). In subsequent phylogenetic analysis, PrVI was grouped together with SNSV and blackberry chlorotic ringspot virus (BCRV), both members of subgroup 1 of ilarviruses. In addition, mini-scale surveys in stone fruit orchards revealed the presence of PrVI in a limited number of sweet cherries and in one peach tree. Overall, our data suggest that PrVI is a novel species of the genus Ilarvirus and it consists the fifth member of the genus that is currently known to infect Prunus spp.

11.
Hum Cell ; 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33860459

RESUMEN

The intraoperative ischemia in partial nephrectomy (PN) often leads to postoperative renal function impairment and fibrosis, which can be regulated by macrophage polarization. We have previously demonstrated that microvesicles derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSC-MVs) attenuated renal ischemia-induced renal fibrosis and contained a substantial quantity of hepatocyte growth factor (HGF). Herein, we investigated whether MSC-MVs regulate macrophage polarization and ameliorate renal fibrosis following ischemia-PN via transferring HGF. A rat model of ischemia-PN was established by 45 min of left renal ischemia followed by removal of 1/3 upper left kidney. MSC-MVs were injected through the tail vein immediately after ischemia. Renal injury biomarkers were measured and histologic analysis was performed to analyze renal injury. A co-culture model of THP-1 macrophages and MSC-MVs was utilized. The expression of M1 markers and M2 markers were determined to evaluate macrophage polarization. MSC-MV administration significantly ameliorated renal inflammation, lesions, and fibrosis in ischemia-PN rats, and promoted M2 macrophage polarization both in rat remnant renal tissues and LPS-treated THP-1 cells. These effects of MSC-MVs were compromised when HGF expression was downregulated in MSC-MVs. Collectively, MSC-MVs promote M2 macrophage polarization and attenuate renal fibrosis following ischemia-PN via transferring HGF.

12.
Neural Netw ; 139: 237-245, 2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33794426

RESUMEN

The existing keyword spotting (KWS) techniques can recognize pre-defined keywords well but have a poor recognition accuracy for user-defined keywords. In real use cases, there is a high demand for users to define their keywords for various reasons. To address the problem, in this work, three techniques have been proposed, including incremental training with revised loss function, data augmentation, and fine-grained training, to improve the accuracy for the user-defined keywords while maintaining high accuracy for pre-defined keywords. The proposed techniques are applied to a classical KWS model (cnn-trad-fpool3) and a state-of-the-art KWS model (res15) respectively. The experimental results show that the proposed techniques have better recognition accuracy than several existing methods for the recognition of use-defined keywords. With the proposed techniques, the recognition accuracy of user-defined keywords on cnn-trad-fpool3 and res15 are significantly improved by 21.78% and 24.42%, respectively.

13.
Int J Biol Sci ; 17(5): 1382-1394, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33867853

RESUMEN

Implant-derived wear particles can be phagocytosed by local macrophages, triggering an inflammatory cascade that can drive the activation and recruitment of osteoclasts, thereby inducing peri-prosthetic osteolysis. Efforts to suppress pro-inflammatory cytokine release and osteoclastsogenesis thus represent primary approaches to treating and preventing such osteolysis. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylases that control diverse metabolic processes. However, whether SIRT3 could mitigate wear debris-induced osteolysis has not been reported. Herein we explored the impact of the SIRT3 on titanium particle-induced osteolysis. Tartrate resistant acid phosphatase (TRAP) staining revealed that the inhibition of SIRT3 suppressed nuclear factor-κB ligand (RANKL)-mediated osteoclasts activation in a dose-dependent fashion. Notably, inhibition of SIRT3 also suppressed matrix metallopeptidase 9 (MMP9) and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) expression at the mRNA and protein levels, while also inhibiting the mRNA expression of dendritic cell-specific transmembrane protein (DC-STAMP), ATPase H+ Transporting V0 Subunit D2 (Atp6v0d2), TRAP and Cathepsin K (CTSK) . In addition, inhibition of SIRT3 suppressed titanium particle-induced tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) expression and prevented titanium particle-induced osteolysis and bone loss in vivo. This inhibition of osteoclasts differentiation was found to be linked to the downregulation and reduced phosphorylation of JNK and ERK. Taken together, inhibition of SIRT3 may be a potential target for titanium particle-induced bone loss.

14.
Nanomaterials (Basel) ; 11(4)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807185

RESUMEN

Brucella is a foodborne pathogen globally affecting both the economy and healthcare. Surface Enhanced Raman Spectroscopy (SERS) nano-biosensing can be a promising strategy for its detection. We combined high-performance quasi-crystal patterned nanocavities for Raman enhancement with the use of covalently immobilized Tbilisi bacteriophages as high-performing bio-receptors. We coupled our efficient SERS nano-biosensor to a Raman system to develop an on-field phage-based bio-sensing platform capable of monitoring the target bacteria. The developed biosensor allowed us to identify Brucella abortus in milk by our portable SERS device. Upon bacterial capture from samples (104 cells), a signal related to the pathogen recognition was observed, proving the concrete applicability of our system for on-site and in-food detection.

15.
Med Sci Monit ; 27: e930853, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33844678

RESUMEN

BACKGROUND COVID-19 has become a worldwide epidemic disease and is a public health crisis. We aim to provide evidence for clinical diagnosis and assessment of severity by analyzing patients' clinical data and early laboratory results and exploring the correlation between laboratory results and clinical classification. MATERIAL AND METHODS We enrolled 283 cases of suspected and diagnosed COVID-19 from 16 hospitals in Jiangsu Province from January to April 2020. The routine laboratory blood examinations, T lymphocyte subsets, and biochemical and coagulation function among different populations were contrasted by t test and chi-square (χ²) test. RESULTS Cough, fever, and dyspnea could be helpful to diagnose COVID-19 infection (P<0.05). Patients who were older or had comorbidities tended to become severe and critical cases. Among all the patients, the most obvious abnormal laboratory results were higher neutrophil count, CRP, total bilirubin, BUN, CRE, APTT, PT, and D-dimer, and lower blood platelet and lymphocyte count. CD3⁺ T cell, CD4⁺ T cell, and CD8⁺ T cell counts gradually decreased with exacerbation of the disease (P<0.05). CONCLUSIONS Cough and fever were the most common symptom. Patients with comorbidities were in more serious condition. The detection of inflammatory indexes, coagulation function, lymphocyte subsets, and renal function can help diagnose and assess the severity of COVID-19.

16.
J Biol Chem ; : 100644, 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33839152

RESUMEN

Exposure of mucosal epithelial cells to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is known to disrupt epithelial cell junctions by impairing stathmin-mediated microtubule depolymerization. However, the pathological significance of this process and its underlying molecular mechanism remain unclear. Here we show that treatment of epithelial cells with pseudotyped HIV-1 viral particles or recombinant gp120 protein results in the activation of protein kinase G 1 (PKG1). Examination of epithelial cells by immunofluorescence microscopy reveals that PKG1 activation mediates the epithelial barrier damage upon HIV-1 exposure. Immunoprecipitation experiments show that PKG1 interacts with stathmin and phosphorylates stathmin at serine 63 in the presence of gp120. Immunoprecipitation and immunofluorescence microscopy further demonstrate that PKG1-mediated phosphorylation of stathmin promotes its autophagic degradation by enhancing the interaction between stathmin and the autophagy adaptor protein p62. Collectively, these results suggest that HIV-1 exposure exploits the PKG1/stathmin axis to affect the microtubule cytoskeleton and thereby perturbs epithelial cell junctions. Our findings reveal a novel molecular mechanism by which exposure to HIV-1 increases epithelial permeability, which has implications for the development of effective strategies to prevent mucosal HIV-1 transmission.

17.
Dent Mater J ; 2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33642446

RESUMEN

It is crucial to emphasize the biomineralization therapeutic method to repair etched dentin in clinic. Non-collagenous proteins (NCPs) play critical role in the biomineralization of dentine. In this paper, we synthesized the phosphate-terminated polyamidoamine dendrimer (PAMAM-PO3H2) by one-step modification successfully and examined by Fourier-transform infrared spectroscopy (FTIR) and 1H-nuclear Magnetic Resonance (1H-NMR) to characterize the structure of PAMAM-PO3H2. PAMAM-PO3H2 and carboxylterminated dendrimers (PAMAM-COOH) were applied as the dual biomimetic analogs of NCPs. Through the characterization of FT-IR, field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD), the surfaces of human dentin were covered with regenerated crystals and the dentinal tubules were occluded by PAMAM-PO3H2 and PAMAM-COOH. In summary, the combination of PAMAM-PO3H2 and PAMAM-COOH may be another feasible therapeutic method for the treatment of dentin caries and dentin hypersensitivity.

19.
Mol Med Rep ; 23(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33649860

RESUMEN

Vascular endothelial dysfunction is a vital pathological change in hypertension, which is mainly caused by apoptosis and oxidative stress injury of vascular endothelial cells. Peptidomics is a method for the direct analysis of small bioactive peptides in various biological samples using liquid chromatography­mass spectrometry (MS)/MS. Given the advantages of the low molecular weight, optimum targeting and easy access to cells, peptides have attracted extensive attention in the field of drug research. However, to the best of our knowledge, little is currently known regarding the role of peptides in vascular endothelial injury. In order to investigate the peptides involved in vascular endothelial protection, MS was used to analyze the peptide profiles in the supernatant of human umbilical vein endothelial cells (HUVECs) stimulated by Ang II. The results revealed that 211 peptides were identified, of which six were upregulated and 13 were downregulated when compared with the control group. Subsequently, the present study analyzed the physical and chemical properties and biological functions of identified peptides by bioinformatics, and successfully screened a peptide (LLQDSVDFSLADAINTEFK) named VMP­19 that could alleviate the apoptosis and oxidative stress injury of HUVECs induced by Ang II. In conclusion, to the best of our knowledge, the present study was the first to use peptidomics to analyze the peptide profiles of supernatant secreted by HUVECs, and revealed that the novel peptide VMP­19 could protect HUVECs from apoptosis and oxidative stress injury. The results of the present study could provide novel insights into treatment strategies for hypertension.

20.
J Endod ; 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33775732

RESUMEN

INTRODUCTION: Regenerative endodontics have created a desirable shift in treatment paradigm, despite current limitations of regenerative outcomes. Mesenchymal stem cells (MSCs) facilitate tissue regeneration and repair in a mild inflanmmatory environment. Small extracellular vesicles (sEVs) derived from MSCs play an imperative role in the paracrine modulation of regenerative responses modulated by MSCs. However, it remains unknown whether MSCs enhance dental pulp regeneration or whether this enhancement is mediated by sEVs in mild inflammatory environment. The present study aimed to elucidate the effects of sEVs originated from lipopolysaccharide (LPS)-preconditioned human dental pulp stem cells (hDPSCs) on dental pulp regeneration. METHODS: All sEVs were isolated from hDPSCs cultured with or without LPS; N-sEVs and L-sEVs, respectively. The effect of N-sEVs and L-sEVs on proliferation, migration, angiogenesis, and differentiation of rat bone marrow MSCs (BMSCs) was identified in vitro. Moreover, N-sEVs or L-sEVs were implanted into rat pulpless root canal models, and the regenerated tissue in root canals was assessed via hematoxylin and eosin staining, Masson staining, and immunohistochemistry (IHC) after 30 days of transplantation. RESULTS: Both N-sEVs and L-sEVs could modulate BMSCs proliferation, migration, angiogenesis, and differentiation. Both kinds of sEVs enhanced the structure of the regenerated tissue closer to that of a normal dental pulp in vivo. L-sEVs had a more significant effect than N-sEVs. CONCLUSIONS: sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating the regeneration of dental pulp through functional healing instead of scar healing, which has potential applications as in regenerative endodontics.

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