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1.
J Cardiothorac Surg ; 16(1): 296, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629094

RESUMO

BACKGROUND: Hepatic dysfunction (HD) increases the morbidity and mortality rates after cardiac surgery. However, few studies have investigated the association between HD and acute DeBakey type I aortic dissection (ADIAD) surgery. This retrospective study aimed to identify risk factors for developing HD in patients who received acute type I aortic dissection repair and its consequences. METHODS: A total of 830 consecutive patients who received ADIAD surgery from January 2014 to December 2019 at our center were screened for this study. The End-Stage Liver Disease (MELD) score more than 14 was applied to identify postoperative HD. Logistic regression model was applied to identify risk factors for postoperative HD, Kaplan-Meier survival analysis and Cox proportional hazards regression assay were conducted to analyze the association between HD and postoperative long-term survival. RESULTS: Among 634 patients who eventually enrolled in this study, 401 (63.2%) experienced postoperative HD with a 30-Day mortality of 15.5%. Preoperative plasma fibrinogen level (PFL) [odds ratio (OR): 0.581, 95% confidence interval (CI): 0.362-0.933, P = 0.025], serum creatinine (sCr) on admission (OR: 1.050, 95% CI 1.022-1.079, P < 0.001), cardiopulmonary bypass (CPB) time (OR: 1.017, 95% CI 1.010-1.033, P = 0.039), and postoperative mechanical ventilation (MV) duration (OR: 1.019, 95% CI 1.003-1.035, P = 0.020) were identified as independent risk factors for developing postoperative HD by multivariate analyses. In addition, the Kaplan-Meier analysis indicated that the long-term survival rate was significantly different between patients with or without postoperative HD. However, the hazard ratios of long-term survival for these two groups were not significantly different. CONCLUSIONS: HD was a common complication after ADIAD surgery and associated with an increasing 30-Day mortality rate. Decreased PFL, elevated sCr, prolonged CPB duration, and longer postoperative MV time were independent risk factors for postoperative HD.

2.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34576007

RESUMO

Seedless fruit is a feature appreciated by consumers. The ovule abortion process is highly orchestrated and controlled by numerous environmental and endogenous signals. However, the mechanisms underlying ovule abortion in pear remain obscure. Here, we found that gibberellins (GAs) have diverse functions during ovules development between seedless pear '1913' and seeded pear, and that GA4+7 activates a potential programmed cell death process in '1913' ovules. After hormone analyses, strong correlations were determined among jasmonic acid (JA), ethylene and salicylic acid (SA) in seedless and seeded cultivars, and GA4+7 treatments altered the hormone accumulation levels in ovules, resulting in significant correlations between GA and both JA and ethylene. Additionally, SA contributed to ovule abortion in '1913'. Exogenously supplying JA, SA or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid promoted 'Bartlett' seed death. The regulatory mechanism in which ethylene controls ovule death has been demonstrated; therefore, JA's role in regulating '1913' ovule abortion was investigated. A further study identified that the JA signaling receptor MYC2 bound the SENESCENCE-ASSOCIATED 39 promoter and triggered its expression to regulate ovule abortion. Thus, we established ovule abortion-related relationships between GA and the hormones JA, ethylene and SA, and we determined their synergistic functions in regulating ovule death.

3.
Int J Nanomedicine ; 16: 6455-6475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584411

RESUMO

Purpose: Prepare a multifunctional ultrasound molecular probe, cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (iRGD-ICG-10-HCPT-PFP-NPs), and to combine iRGD-ICG-10-HCPT-PFP -NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Materials and Methods: The morphology of nanoparticles (NPs) and iRGD-ICG-10-HCPT-PFP-NPs was detected. In vitro, we examined targeting ability by flow cytometry and confocal laser scanning microscopy (CLSM), assessed penetration ability into hepatoma cells, and assessed killing ability. In vivo, we examined the targeting ability of the NPs with a photoacoustic (PA) imager and fluorometer (FL), while LIFU irradiation was used to trigger the release of chemotherapeutic drugs, which had a therapeutic effect on tumors. Results: The particle size of iRGD-ICG-10-HCPT-PFP-NPs was 298.4 ± 10.42 nm. In vitro, iRGD-ICG-10-HCPT-PFP-NPs bound more to SK-Hep1 cells than ICG-10-HCPT-PFP-NPs. iRGD-ICG-10-HCPT-PFP-NPs could achieve PA/ultrasound imaging. The percentage of antiproliferative and apoptotic cells in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly higher. In vivo, iRGD-ICG-10-HCPT-PFP-NPs can target tumor sites and achieve PA/ultrasound imaging. The tumor volume in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly smaller, and the antiproliferative and proapoptotic effects were higher. Conclusion: We successfully prepared a novel molecular probe that has good targeting, can perform ultrasound/PA dual-modality imaging, and can penetrate deep into tumors to achieve better therapeutic tumor effects, providing a new idea and method for theranostics of HCC.

4.
Int J Biol Sci ; 17(13): 3522-3537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512163

RESUMO

Of all pathological types of renal cell cancer (RCC), clear cell renal cell carcinoma (ccRCC) has the highest incidence. Cyclovirobuxine (CVB), a triterpenoid alkaloid isolated from Buxus microphylla, exhibits antitumour activity against gastric cancer and breast cancer; however, the mechanism by which CVB inhibits ccRCC remains unclear. The aim of our study was to explore the antitumour effects of CVB on ccRCC and to elucidate its exact mechanism. Cell viability, proliferation, cell cycle distribution, apoptosis, wound healing and invasion were evaluated. Furthermore, Western blotting, immunofluorescence staining, immunohistochemical staining, and bioinformatics analyses were utilized to comprehensively probe the molecular mechanisms. The in vivo curative effect of CVB was explored using a 786-O xenograft model established in nude mice. CVB reduced cell viability, proliferation, angiogenesis, the epithelial-mesenchymal transition (EMT), migration and invasion. In addition, CVB induced cell cycle arrest in S phase and promoted apoptosis. The expression of the EMT-related transcription factor Snail was significantly downregulated by CVB via the inhibition of the AKT, STAT3 and MAPK pathways. We revealed that insulin-like growth factor binding protein 3 (IGFBP3) was the true therapeutic target of CVB. CVB exerted anti-ccRCC effects by blocking the IGFBP3-AKT/STAT3/MAPK-Snail pathway. Targeted inhibition of IGFBP3 with CVB treatment may become a promising therapeutic regimen for ccRCC.

5.
J Phys Chem Lett ; 12(36): 8713-8719, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34473516

RESUMO

In this work, we investigate the relationship between the charge distribution and electron occupation by exploring neutral gold superatoms Aun and their anion structures [Aun]- (n = 13, 55, and 147). It is shown that there exists "skin behavior" of charge distribution for gold superatoms. For the neutral Aun, there are negative charges of -0.1 e, -0.54 e, and -1.16 e distributed in the surface area of 1D5 SAMOs of Au13, 1F12 1G15 SAMOs of Au55, and 2D6 1H22 2F14 1I6 3S2 1J6 1I8 1J4 3P1 SAMOs of Au147, respectively. For the anion [Aun]-, more negative charges of -1.08 e, -1.55 e, and -2.14 e are distributed in the surface area of 1D SAMO of [Au13]-, 1G SAMO of [Au55]-, and 3P SAMO of [Au147]-. In addition, adding an electron will cause the SAMOs rearrangement and enhance the geometric symmetry of superatoms, especially in [Au13]- and [Au55]-. Our findings provide a new perspective on microelectronic structure in understanding the skin effects.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Ânions/química , Simulação por Computador , Técnicas Eletroquímicas , Elétrons , Propriedades de Superfície
6.
Genes Genomics ; 43(11): 1307-1316, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34524611

RESUMO

BACKGROUND: Gastric cell carcinoma (GCC) is a common and high-incidence malignant gastrointestinal cancer that seriously threatens human life and safety. Evidences suggest that microRNAs (miRNAs) exhibit an essential role in regulating the occurrence and development of GCC, while the effects and possible mechanisms remain to be further explored. OBJECTIVE: This study was designed to explore whether miR-200c-3p exerted its functional role in the growth and metastasis of GCC, and investigate the possible mechanisms. METHODS: The expression levels of miR-200c-3p in GCC tissues and cell lines were detected by qRT-PCR analysis. The functional role of miR-200c-3p in the viability, proliferation, migration and invasion of GCC cells were evaluated by CCK-8, EdU, wound healing and Transwell assays. In addition, the candidate targets of miR-200c-3p was predicted and confirmed by dual-luciferase reporter assay. Moreover, the relationship between miR-200c-3p and target (Krüppel like factor 6, KLF6) was assessed by qRT-PCR and western blot assays. Besides, the expression levels of KLF6 in GCC cells were determined by qRT-PCR and western blot assays. Furthermore, the role of KLF6 in the viability, proliferation, migration and invasion of GCC cells mediated with miR-200c-3p mimics was evaluated by CCK-8, EdU, wound healing and Transwell assays. RESULTS: In the present study, a new tumor promoting function of miR-200c-3p was disclosed in GCC. We found that the expression of miR-200c-3p was obviously increased in clinic GCC tissues and cell lines. In addition, down-regulation of miR-200c-3p suppressed cell viability, proliferation, migration, and invasion in GCC cells. Moreover, KLF6 was verified as a direct target of miR-200c-3p by binding its 3'-UTR. Additionally, KLF6 was remarkably decreased and was negatively associated with the miR-200c-3p expression in GCC cell lines. Furthermore, over-expression of KLF6 retarded the effects of miR-200c-3p on the growth and metastasis of GCC cell lines. CONCLUSIONS: MiR-200c-3p potentially played a tumor-promoting role in the occurrence and development of GCC, which may be achieved by targeting KLF6.

7.
Nat Commun ; 12(1): 5323, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493722

RESUMO

The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the promoter, thereby promoting dietary fat absorption. Supporting these findings, intestinal deficiency of Rev-erbα, a known BMAL1 repressor, enhances dietary fat absorption and exacerbates HFD-induced obesity and comorbidities. Moreover, small-molecule targeting of REV-ERBα/BMAL1 by SR9009 ameliorates HFD-induced obesity in mice. Altogether, intestine clock functions as an accelerator in dietary fat absorption and targeting intestinal BMAL1 may be a promising approach for management of metabolic diseases induced by excess fat intake.


Assuntos
Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/genética , Diacilglicerol O-Aciltransferase/genética , Fígado Gorduroso/genética , Hiperlipidemias/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Obesidade/genética , Fatores de Transcrição ARNTL/deficiência , Animais , Diacilglicerol O-Aciltransferase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Regulação da Expressão Gênica , Homeostase/efeitos dos fármacos , Homeostase/genética , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Regiões Promotoras Genéticas , Ligação Proteica , Pirrolidinas/farmacologia , Transdução de Sinais , Tiofenos/farmacologia , Triglicerídeos/biossíntese
8.
Biosens Bioelectron ; 194: 113594, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34474280

RESUMO

Gastric cancer cell-derived exosomes as biomarkers have a very high application potential to the non-invasive detection of early-stage gastric cancer. However, the small size of exosomes (30-150 nm) results in huge challenges in separating and detecting them from complex media (e.g., plasma, urine, saliva, and cell culture supernatant). Here we proposed a highly integrated exosome separation and detection (ExoSD) chip to immunomagnetic separate exosomes from cell culture supernatant in a manner of continuous flow, and to immunofluorescence detect gastric cancer cell-derived exosomes with high sensitivity. The ExoSD chip has achieved a high exosome recovery (>80%) and purity (>83%) at the injection rate of 4.8 mL/h. Furthermore, experimental results based on clinical serum samples of patients with gastric cancer (stages I and II) show that the detection rate of the ExoSD chip is as high as 70%. The proposed ExoSD chip has been successfully demonstrated as a cutting-edge platform for exosomes separation and detection. It can be served as a versatile platform to extend to the applications of separation and detection of the other cell-derived exosomes or cells.

9.
Aging Cell ; : e13461, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499402

RESUMO

Bone marrow-derived mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are potent candidates for the suppression of acute rejection post-renal allograft and have been reported to halt dendritic cells (DCs) maturation. However, whether BMSC-derived sEVs mitigate acute rejection post-renal allograft by targeting DCs is still unclear. In this study, donor BMSC-derived sEVs (sEVs) relieved the inflammatory response and suppressed mature DCs (mDCs) location in kidney grafts, and increased regulatory T (Treg) cell population in the spleens of the rats that underwent kidney allograft. In lipopolysaccharide (LPS)-stimulated immature DCs (imDCs), sEVs suppressed the maturation and migration of DCs and inactivated toll-like receptor 4 (TLR4) signaling. Compared with LPS-treated imDCs, imDCs treated with LPS+sEVs promoted CD4+ T cells differentiated toward Treg cells. Subsequently, we found that Loc108349490, a long non-coding RNA (lncRNA) abundant in sEVs, mediated the inhibitory effect of sEVs on DC maturation and migration by promoting TLR4 ubiquitination. In rats that underwent an allograft, Loc108349490 deficiency weakened the therapeutic effect of sEVs on acute rejection. The present study firstly found that sEVs alleviated acute rejection post-renal allograft by transferring lncRNA to DCs and screened out the functional lncRNA loaded in sEVs was Loc108349490.

10.
Sci Rep ; 11(1): 17846, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497313

RESUMO

We studied the effects of leaf surface characteristics on canopy droplet behaviour using two rice cultivars with similar leaf shapes but significantly different leaf surface characteristics: Jia58 (glabrous rice; smooth leaf surface and no burrs) and Yongyou12 (hairy-leaved rice; rough leaf surface covered with burrs). The plants were subjected to spray tests with different spray pressures and nozzle apertures. The results showed that the deposition amount per unit leaf area was significantly higher in the Yongyou12 canopy than in the Jia58 canopy. The diameter, volume median diameter, number median diameter, and coverage of droplets were significantly higher in Yongyou12 than in Jia58, while the coverage density of droplets was significantly lower. The proportion of small droplets of Jia58 is higher than that of Yongyou12. Thus, a larger amount of large-sized droplets could retain on the leaf surface of hairy-leaved rice, and a larger number of small-sized droplets were retained on the leaf surface of glabrous rice. Smaller pressure and larger flow nozzle were conducive to the retention of the Jia58, while Yongyou12 required larger pressure and larger flow nozzles. Ultrastructural analyses revealed that the leaf surface of glabrous rice had no trichomes and more wax than hairy-leaved rice, and the critical surface tension was lower, resulting in the retention of mainly small droplets on its leaf surface and a lower deposition amount. Therefore, in order to increase the deposition of pesticide droplets on the leaf surface in production, glabrous rice should choose nozzles with smaller spray pressure and large flow rate.

11.
Physiol Plant ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418106

RESUMO

Anthocyanins are common secondary metabolites in plants that impart red coloration to fruits and flowers. The important WRKY transcription factor family plays multifaceted roles in plant growth and development. In this study, we found a WRKY family gene, Pyrus bretschneideri WRKY75, that may be involved in anthocyanin synthesis in pear. Unlike Arabidopsis thaliana WRKY75, PbWRKY75 may be a positive regulator of anthocyanin synthesis. A transient expression assay indicated that PbWRKY75 promoted pear anthocyanin synthesis. The structural genes (PbANS, PbDFR, and PbUFGT) and positive regulators (PbMYB10 and PbMYB10b) of anthocyanin synthesis were significantly upregulated in the fruitlet skins of PbWRKY75-overexpressing "Zaosu" pears. Subsequently, yeast one-hybrid and dual-luciferase assays indicated that PbWRKY75 promoted PbDFR, PbUFGT, and PbMYB10b expression by activating their promoters. These results revealed that PbWRKY75 may promote the expression of both PbMYB10b and anthocyanin late biosynthetic genes (PbDFR and PbUFGT) by activating their promoters, thereby inducing anthocyanin synthesis in pear. This study enhanced our understanding of the mechanism of pear anthocyanin synthesis, which will be beneficial in the improvement of pear peel color.

13.
Orthop Surg ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351059

RESUMO

OBJECTIVE: To investigate the outcomes of C-shaped release around the greater trochanter in gluteal muscle contracture under arthroscopy. METHODS: From December 2016 to January 2018, 185 patients with gluteal muscle contracture who treated under arthroscopy were reviewed, including 69 males and 116 females. All patients had a history of repeated intramuscular injection into the buttocks. The follow signs were positive in all the patients before surgery: squatting and crouching disability, difficulty in crossing the leg, Ober's sign positive, clicking sound during rotation of the hip. The C-shaped release around the greater trochanter under arthroscopy was performed in 96 cases (C-shaped release group) with an average age of 24.6 ± 4.9 years old, and conventional gluteal muscle contracture release under arthroscopy was performed in 89 cases (conventional release group) with an average age of 25.1 ± 5.0 years. The released tissues in the C-shaped release group: iliotibial band (ITB) about 5 cm distal to the proximal end of the greater trochanter, the contracture tissue near the posterior and superior of the greater trochanter, which depended on both intraoperative physical examination and arthroscopic observation. The released tissues in conventional release group: the contracture tissues in gluteal muscles according to observation under arthroscopy. The gluteal muscle contracture disability scale (GDS) and Visual analogue scale (VAS) were evaluated before surgery and at the last follow-up. RESULTS: The average release time after making arthroscopic operation space for each lower limb were 12.2 ± 3.2 min in the C-shaped release group, and 21.4 ± 6.1 min in the conventional release group (P = 0.000). All the patients were followed for at least of 2 years after operation. There was one case of wound hematoma in the C-shaped release group and five cases in the conventional release group(P = 0.079), abductor weakness (IV level)occurred in two patients in the C-shaped release group and five cases in the conventional release group (P = 0.208). GDS was 49.3 ± 17.3 (22 to 70) in theC-shaped release group and 48.1 ± 15.6 (23 to 69) in the conventional release group before surgery (P = 0.622), 91.7 ± 5.2 (83 to 100) in the C-shaped release group and 90.2 ± 6.1 (83 to 98) in the conventional release group (P = 0.073) with difference nearly significant at last follow-up. CONCLUSION: Arthroscopic C-shaped release around the greater trochanter had less operation time, acceptable complication occurrence, and it has an optimistic outcome for gluteal muscle contracture under arthroscope.

14.
Biomater Sci ; 9(18): 6126-6141, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34378578

RESUMO

Sonodynamic therapy (SDT) is a fast-growing therapy activated by using ultrasound to initiate a catalytic reaction of sensitizing agents and kill tumor cells through producing reactive oxygen species (ROS). Both sinoporphyrin sodium (DVDMS) and IR780 are preeminent sonosensitizers and have been used in SDT alone. In this study, tumor targeting multifunctional composite nanoparticles (DVDMS@IR780@PFP@PLGA, DIPP-NPs) were synthesized by encapsulating DVDMS, IR780 and perfluoropentane (PFP) to synergistically enhance SDT and achieve imaging of tumors. The loaded IR780 is regarded as a "navigator" to accurately identify and target tumor cells/tissues. DVDMS and IR780 not only can realize the directed SDT, but also can perform photoacoustic (PA) imaging. PFP plays its role in enhancing the ultrasound (US) imaging. Generally, DIPP-NPs not only have an obvious synergistic anti-tumor effect, but also are able to carry out dual-mode imaging, which paves a promising way for tumor therapy.


Assuntos
Nanopartículas , Terapia por Ultrassom , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio
15.
J Environ Sci (China) ; 107: 171-183, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412780

RESUMO

Dimethyl phthalate (DMP), used as a plasticizer in industrial products, exists widely in air, water and soil. Staphylococcus aureus is a typical model organism representing Gram-positive bacteria. The molecular mechanisms of DMP toxicology in S. aureus were researched by proteomic and transcriptomic analyses. The results showed that the cell wall, membrane and cell surface characteristics were damaged and the growth was inhibited in S. aureus by DMP. Oxidative stress was induced by DMP in S. aureus. The activities of succinic dehydrogenase (SDH) and ATPase were changed by DMP, which could impact energy metabolism. Based on proteomic and transcriptomic analyses, the oxidative phosphorylation pathway was enhanced and the glycolysis/gluconeogenesis and pentose phosphate pathways were inhibited in S. aureus exposed to DMP. The results of real-time reverse transcription quantitative PCR (RT-qPCR) further confirmed the results of the proteomic and transcriptomic analyses. Lactic acid, pyruvic acid and glucose were reduced by DMP in S. aureus, which suggested that DMP could inhibit energy metabolism. The results indicated that DMP damaged the cell wall and membrane, induced oxidative stress, and inhibited energy metabolism and activation in S. aureus.


Assuntos
Proteômica , Staphylococcus aureus , Metabolismo Energético , Estresse Oxidativo , Ácidos Ftálicos
16.
Mol Med Rep ; 24(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414457

RESUMO

Colon carcinoma is one of the most common cancers worldwide. Epidemiological studies have revealed that colon cancer is the third leading cause of cancer­related deaths, which is due to the increased incidence and mortality rates. However, the treatment strategies for colon cancer remain unsatisfactory for patients, especially for those with advanced or recurrent colon cancer. Dysregulated microRNAs (miRNAs) are considered to influence tumor development and metastasis. However, the molecular mechanism through which miRNAs affect cancer progression is not yet completely understood. The aim of the present study was to investigate the expression levels of has­miR­15a­5p and its molecular mechanism in colon cell carcinoma. In the present study, the expression levels of hsa­miR­15a­5p were found to be decreased in colon tumor tissues and cancer cell lines. Hsa­miR­15a­5p overexpression inhibited colon cell proliferation and migration. Mechanistically, the G1/S­specific cyclin­D1 (CCND1) gene was predicted as a target of hsa­miR­15a­5p, as evidenced by bioinformatics and dual­luciferase reporter assay analyses. CCND1 overexpression significantly increased the progression of colon cancer. Furthermore, CCND1 was demonstrated to mediate the effects of hsa­miR­15a­5p on colon cancer cells. The present study demonstrated that hsa­miR­15a­5p alleviated the proliferation, migration and invasion of colon cancer by targeting the CCND1 gene, which represents a potential molecular target for the diagnosis and treatment of colon cancer.

17.
Adv Sci (Weinh) ; 8(19): e2100850, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34382370

RESUMO

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/MnFe2 O4 -ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2 O4 ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid-glycolic acid (PLGA) shells and is conjugated to an anti-VEGFR-2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP-mediated SDT promotes mitochondrial-caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP-mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP-mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP-mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.

18.
Int J Cardiol ; 342: 72-81, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311013

RESUMO

Ischemia/reperfusion (I/R) injury is an inevitable process during heart transplant and suppressing I/R injury could greatly improve the survival rate of recipients. Mesenchymal stem cells (MSCs) have positive effects on I/R. We aimed to investigate the mechanisms underlying the protective roles of MSCs in I/R. Both cell model and rat model of myocardial I/R were used. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. QRT-PCR and western blotting were employed to measure levels of lncRNA HCP5 (HLA complex P5), miR-497, apoptosis-related proteins, and insulin-like growth factor (IGF1)/PI3K/AKT pathway. Dual luciferase assay was used to validate interactions of HCP5 and miR-497, miR-497 and IGF1. Echocardiography was performed to evaluate cardiac function of rats. Serum levels of CK-MB and LDH were measured. H&E and Masson staining were used to examine morphology of myocardial tissues. hBMSC-derived exosomes (hBMSC-Exos) increased the viability of cardiomyocytes following hypoxia/reperfusion (H/R) and decreased apoptosis. H/R diminished HCP5 expression in cardiomyocytes while hBMSC-Exos recovered the level. Overexpression of HCP5 in hBMSC-Exos further enhanced the protective effects in H/R while HCP5 knockdown suppressed. HCP5 directly bound miR-497 and miR-497 targeted IGF1. miR-497 mimics or si-IGF1 blocked the effects of HCP5 overexpression. Further, hBMSC-Exos alleviated I/R injury in vivo and knockdown of HCP5 in hBMSC-Exos decreased the beneficial effects. AntagomiR-497 blocked the effects of HCP5 knockdown. HCP5 from hBMSC-Exos protects cardiomyocytes against I/R injury via sponging miR-497 to disinhibit IGF1/PI3K/AKT pathway. These results shed light on mechanisms underlying the protective role of hBMSC-Exos in I/R.

19.
Biomater Sci ; 9(16): 5652-5664, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34259244

RESUMO

Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis.


Assuntos
Nanopartículas , Placa Aterosclerótica , Animais , Linhagem Celular Tumoral , Células Endoteliais , Compostos Férricos , Imagem Multimodal , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Fototerapia , Placa Aterosclerótica/diagnóstico por imagem , Coelhos , Nanomedicina Teranóstica
20.
J Leukoc Biol ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231935

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has now become a pandemic, and the etiologic agent is the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). T cell mediated immune responses play an important role in virus controlling; however, the understanding of the viral protein immunogenicity and the mechanisms of the induced responses are still limited. So, identification of specific epitopes and exploring their immunogenic properties would provide valuable information. In our study, we utilized the Immune Epitope Database and Analysis Resource and NetMHCpan to predict HLA-A2 restricted CD8+ T cell epitopes in structural proteins of SARS-CoV-2, and screened out 23 potential epitopes. Among them, 18 peptides showed strong or moderate binding with HLA-A2 with a T2A2 cell binding model. Next, the mixed peptides induced the increased expression of CD69 and highly expressed levels of IFN-γ and granzyme B in CD8+ T cells, indicating effective activation of specific CD8+ T cells. In addition, the peptide-activated CD8+ T cells showed significantly increased killing to the target cells. Furthermore, tetramer staining revealed that the activated CD8+ T cells mainly recognized seven epitopes. All together, we identified specific CD8+ T cell epitopes in SARS-CoV-2 structural proteins, which could induce the production of specific immune competent CD8+ T cells. Our work contributes to the understanding of specific immune responses and vaccine development for SARS-CoV-2.

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