Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 977
Filtrar
1.
Int J Med Inform ; 157: 104638, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34775213

RESUMO

BACKGROUND: The cytological analysis of bronchoalveolar lavage fluid (BALF) plays an essential role in the differential diagnosis of respiratory diseases. In recent years, deep learning has demonstrated excellent performance in image processing and object recognition. OBJECTIVES: We aim to apply deep learning to the automated interpretation and analysis of BALF. METHOD: Visual images were acquired using an automated biological microscopy platform. We propose a three-step algorithm to automatically interpret BALF cytology based on a convolutional neural network (CNN). The clinical value was evaluated at the patient level. RESULTS: Our model successfully detected most cells in BALF specimens and achieved a sensitivity, precision, and F1 score of over 0.9 for most cell types. In two tests in the clinical context, the algorithm outperformed experienced practitioners. CONCLUSION: The program can automatically provide the cytological background of BALF and augment clinical decision-making for clinicians.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34791515

RESUMO

Mupirocin, a polyketide antibiotic produced by Pseudomonas fluorescens, is used as a topical antimicrobial treatment to cure various skin infections. Quorum sensing system plays an important role in regulation of mupirocin biosynthesis in P. fluorescens NCIMB 10586. In Pseudomonas, the RpeA/RpeB two-component signal transduction (TCST) system regulates quorum sensing system. However, the influences of the RpeA/RpeB TCST system on mupirocin production or other cell activities have not been studied. In this work, the homologous genes of rpeA and rpeB in P. fluorescens NCIMB 10586 were identified and inactivated in the chromosome, respectively. The deletion of rpeA reduced the mupirocin production from 160 in the wild-type to 21.3 mg/L along with slightly decreased cell growth, while no significant effected on mupirocin production in the rpeB mutant. Next, it was found that the RpeA/RpeB TCST system regulated the biosynthesis of mupirocin by modulating the quorum sensing system. Furthermore, untargeted metabolomics analysis was employed to detect the influences of RpeA on other cell activities modulated by quorum sensing system. Combined with quantitative real-time PCR, the results demonstrated that RpeA also regulated other cell activities including central carbon, amino acids, fatty acids, and purine metabolism. Overall, this study expands the current understanding of the RpeA/RpeB TCST system and provides several targets for increasing yields of mupirocin. KEY POINTS: • In P. fluorescens, the RpeA/RpeB TCST system regulates the biosynthesis of mupirocin. • RpeA modulates the cell activities through effecting the central carbon metabolism.

3.
Ophthalmol Ther ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800261

RESUMO

INTRODUCTION: To evaluate the correlation between macular integrity assessment (MAIA) and standard automated perimetry (SAP) in detecting macular function damage in glaucoma and to explore the relationship between macular structure and functional damage by using spectral domain optical coherence tomography (SD-OCT). METHODS: This was a cross-sectional study. Seventy patients with glaucoma, with hemifield defects verified by Humphrey 24-2 examination, and 60 normal subjects underwent Humphrey 10-2 and MAIA expert 10-2 examinations. Patients with glaucoma with normal hemifields, as detected by SAP, were divided into a normal hemifield group and a visual field (VF) defect group. The difference in the retina and ganglion cell complex (GCC) thicknesses was analyzed between the abnormal and normal hemifields. RESULTS: Among the 70 glaucoma eyes, the results of MAIA and SAP were consistent for 66 (66/70, 94.3%). The others showed SAP hemifield defects, while MAIA was normal (4/70, 5.7%). There was a good correlation of the mean sensitivity between MAIA and SAP (P < 0.001). There also was a good correlation between the mean threshold of MAIA and the mean deviation (MD) of SAP (P = 0.008, r = 0.507). Among the patients with glaucoma with a normal hemifield, MAIA showed abnormal results in 50 eyes (50/66, 75.8%), which was consistent with the changes in the inner retina and GCC thicknesses. Meanwhile, MAIA showed normal results; there were no significant differences between patients with glaucoma and the normal group in the thicknesses of the inner retina and GCC. CONCLUSION: MAIA and SAP have good consistency in detecting macular dysfunction. MAIA can also identify abnormal VFs in the macular regions that may not be detected by SAP, which is consistent with the changes in the GCC thicknesses, suggesting that there may be central VF damage in patients with glaucoma that has not been previously identified.

4.
Nanomedicine (Lond) ; 16(27): 2411-2430, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34749510

RESUMO

Background: Chemotherapeutic drugs are associated with toxic effects. Metastasis is the leading cause of death in breast cancer patients. Aim: To evaluate the antitumor effect of paclitaxel (PTX) combined with psoralen-loaded polymeric lipid nanoparticles (PSO-PLNs) in triple-negative breast cancer. Methods: After treatment of samples, cell viability, apoptosis, migration, invasion, expression of proteins in the IRAK1/NF-κB/FAK signal pathway, biodistribution and pathological characteristics were detected. Results: Compared with the control group, the PTX + PSO-PLNs group showed increased apoptosis and reduced migration, invasion and expression of phosphorylated IRAK1 and NF-κB, with significant inhibition of tumor growth and lung metastases and no obvious toxicity. Conclusion: Combined administration of PTX and PSO-PLNs exerted a synergistic effect and significantly inhibited the growth and metastasis of triple-negative breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Paclitaxel/farmacologia , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Linhagem Celular Tumoral , Feminino , Ficusina , Humanos , Lipídeos , Camundongos Endogâmicos BALB C , Distribuição Tecidual , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
5.
Front Genet ; 12: 783128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804131

RESUMO

Given the limitation of technologies, the subcellular localizations of proteins are difficult to identify. Predicting the subcellular localization and the intercellular distribution patterns of proteins in accordance with their specific biological roles, including validated functions, relationships with other proteins, and even their specific sequence characteristics, is necessary. The computational prediction of protein subcellular localizations can be performed on the basis of the sequence and the functional characteristics. In this study, the protein-protein interaction network, functional annotation of proteins and a group of direct proteins with known subcellular localization were used to construct models. To build efficient models, several powerful machine learning algorithms, including two feature selection methods, four classification algorithms, were employed. Some key proteins and functional terms were discovered, which may provide important contributions for determining protein subcellular locations. Furthermore, some quantitative rules were established to identify the potential subcellular localizations of proteins. As the first prediction model that uses direct protein annotation information (i.e., functional features) and STRING-based protein-protein interaction network (i.e., network features), our computational model can help promote the development of predictive technologies on subcellular localizations and provide a new approach for exploring the protein subcellular localization patterns and their potential biological importance.

6.
Front Oncol ; 11: 743077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722295

RESUMO

MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies.

7.
Cell Tissue Res ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725717

RESUMO

RNA N6-methyladenosine (m6A) is essential for many bioprocesses in many species, but its role in goat testis development remains elusive, especially alkB homolog 5 (ALKBH5), one of the m6A demethylases. To this end, nine healthy Haimen goats of different ages were chosen randomly to provide testes. The results showed that the expression level of ALKBH5 was increased significantly (P < 0.05) in the 9-month group compared with the 0-day and 3-month groups, and ALKBH5 was located in goat spermatocytes with the highest expression level compared with Leydig cells and Sertoli cells. Thus, pcDNA3.1-ALKBH5 was constructed to explore the influences of the ALKBH5 increase in goat spermatogonial stem cells (SSC) in vitro. The results showed that the expression level of ALKBH5 in SSC transfected with pcDNA3.1-ALKBH5 (OE_ALKBH5) was significantly increased (P < 0.001) compared with that in SSC transfected with pcDNA3.1-EGFP (EGFP). With ALKBH5 overexpression in SSC, flow cytometry analysis showed that cells at G1 phase were significantly reduced (P < 0.01), while cells at S phase significantly increased (P < 0.01), and cell apoptosis was inhibited. Accordingly, the mRNA degradation of CCND1, CCNE1, and BCL2 was suppressed with ALKBH5 overexpression in SSC after treatment with actinomycin D. Furthermore, the mRNA levels of pluripotency maintenance- and cell differentiation-associated genes were changed between the two groups. Overall, the results indicated the crucial role of ALKBH5 during Haimen goat testis development. The results of this study provide a theoretical basis and technical means for RNA methylation participating in goat testis development.

8.
Front Immunol ; 12: 727750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721390

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune disease of the central nervous system, mainly targets the optic nerve and spinal cord. To date, all attempts at the establishment of NMOSD animal models have been based on neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and mimic the disease in part. To solve this problem, we developed a rodent model by opening the blood-brain barrier (BBB) with low frequency ultrasound, followed by injection of NMO-IgG from NMOSD patients and complement to mice suffering pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis (EAE). In this study, we showed that ultrasound with NMO-IgG and complement caused marked inflammation and demyelination of both spinal cords and optic nerves compared to blank control group, as well as glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) loss of spinal cords and optic nerves compared to EAE mice and EAE mice with only BBB opening. In addition, magnetic resonance imaging (MRI) revealed optic neuritis with spinal cord lesions. We further demonstrated eye segregation defects in the dorsal lateral geniculate nucleus (dLGN) of these NMOSD mice.


Assuntos
Proteínas do Sistema Complemento/imunologia , Encefalomielite Autoimune Experimental/imunologia , Imunoglobulina G/imunologia , Neuromielite Óptica/imunologia , Animais , Aquaporina 4/metabolismo , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/diagnóstico por imagem , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/metabolismo , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/imunologia , Nervo Óptico/metabolismo , Medula Espinal/diagnóstico por imagem , Medula Espinal/imunologia , Medula Espinal/metabolismo , Ondas Ultrassônicas
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(9): 1110-1115, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34839871

RESUMO

OBJECTIVE: To investigate the possible mechanism of ultrasound therapy in the rat model of sepsis. METHODS: Seventy-eight male Sprague-Dawley (SD) rats were randomly divided into Sham group (n = 12), septic model group (n = 22), ultrasound treatment group (n = 22), methyllycaconitine citrate (MLA) combined with ultrasound treatment group (n = 22). In the Sham group, only the abdomen was opened, the cecum was found to be free, without cecal ligation and puncture (CLP). In the septic model group, CLP was used to replicate the septic rat model. After operation, each group of rats were subcutaneously injected with preheated 37 centigrade normal saline. The rats in the ultrasound treatment group were treated with ultrasound [Philips IU22 L9-3 ultrasound instrument and 9 MHz probe were used to break the sequence in the spleen area once every 6 seconds, with 1 second for each time, the mechanical index (MI) was 0.72, and the treatment time was 10 minutes]. In the MLA combined with ultrasound treatment group, α7 nicotinic acetylcholine receptor (α7nAChR) specific blocker MLA 4 mg/kg was injected intraperitoneally 30 minutes before operation, and ultrasound treatment was performed 2 hours after operation. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-1ß, IL-6) in serum of each group were measured by enzyme-linked immunosorbent assay (ELISA) at 24 hours after operation. The 10-day survival rate of each group was recorded, and the symptoms of each group were evaluated by clinical disease score (CDS). The histopathological changes of lung and colon were observed under light microscope. RESULTS: Compared with the Sham group, the 10-day survival rate of rats in the septic model group was decreased significantly [40% (4/10) vs. 100% (6/6)], the CDS was (10.73±2.19 vs. 6.17±0.58) and the levels of TNF-α, IL-6, and IL-1ß were increased significantly at 24 hours after operation [TNF-α (ng/L): 42.00±8.92 vs. 13.16±3.19, IL-6 (ng/L): 129.37±25.04 vs. 63.99±12.92, IL-1ß (ng/L): 254.98±67.27 vs. 76.83±25.39, all P < 0.01]. Compared with the septic model group, the survival rate in the ultrasound treatment group was improved [70% (7/10) vs. 40% (4/10)], but there was no significant difference (P > 0.05). The CDS (7.64±2.68 vs. 10.73±2.19) and the expressions of TNF-α, IL-6, and IL-1ß were significantly reduced at 24 hours after operation [TNF-α (ng/L): 16.93±6.02 vs. 42.00±8.92, IL-6 (ng/L): 73.65±24.38 vs. 129.37±25.04, IL-1ß (ng/L): 111.86±14.08 vs. 254.98±67.27, all P < 0.01]. Compared with the ultrasound treatment group, the survival rate in the MLA combined with ultrasound treatment group was reduced [60% (6/10) vs. 70% (7/10)], but the difference was not statistically significant (P > 0.05). CDS was significantly increased (9.55±2.72 vs. 7.64±2.68), and the levels of TNF-α, IL-6 and IL-1ß were significantly increased at 24 hours after operation [TNF-α (ng/L): 34.61±7.89 vs. 16.93±6.02, IL-6 (ng/L): 112.92±10.42 vs. 73.65±24.38, IL-1ß (ng/L): 212.57±32.16 vs. 111.86±14.08, all P < 0.01]. Microscopically, in the septic model group, the alveolar septum was thickened, a large number of inflammatory cells infiltrated, normal pulmonary reticular structure disappeared, and pulmonary interstitium showed obvious hemorrhage and edema, meanwhile, the structure of colonic villi was obviously abnormal, with cells were edema and inflammatory cell infiltration, and the arrangement was disordered, so that the subepithelial space and the top of it fell off. After ultrasound treatment, the thickness of the alveolar interval in rats was similar to that in Sham group, without obvious inflammatory cell infiltration, and the pulmonary reticular structure was relatively intact. At the same time, the morphology of colonic villi was basically normal and orderly, the edema of cell was not obvious, and subcutaneous space and tip fall off were not obvious. After being antagonized by MLA, the rat lung tissue showed thickened alveolar septum, inflammatory cell infiltration, incomplete pulmonary network structure, hemorrhage and edema in the interstitium. The villi structure of the colon was faintly visible, with obvious cell edema and inflammatory cell infiltration, and the arrangement was abnormal. CONCLUSIONS: Ultrasound treatment improves the prognosis of septic rats, MLA can reverse the anti-inflammatory effect of ultrasound therapy by antagonizing α7nAChR, suggesting that the protective mechanism of ultrasound in sepsis may be related to activating the cholinergic anti-inflammatory pathway mediated by α7nAChR.


Assuntos
Sepse , Animais , Ceco , Mucosa Intestinal , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/terapia , Fator de Necrose Tumoral alfa
10.
Environ Pollut ; : 118570, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843857

RESUMO

The geochemistry of iron (Fe), manganese (Mn) and sulfur (S) and their effects on arsenic (As) mobility in the mudflats of small river estuaries remain unclear. Here, diffusive gradient in thin films (DGT) and high-resolution dialysis (HR-Peeper) techniques combined with a sequential extraction procedure (BCR) were employed to investigate As, Fe, Mn and S geochemistry in the mudflat of the Jiuxi River estuary, Southeast China. Grain size analysis indicated that fine-grained particles were likely to be deposited in the estuarine intertidal zone and coastal area. DGT and HR-Peeper results revealed that in the estuary and coastal area, the dissolved As in sediment in summer was controlled by Mn geochemistry, which includes not only the release of As through Mn/Fe reduction but also the stabilization of dissolved As in pore water. This stabilization of dissolved As may due to the formation of As-Mn-OM complexes. In winter, the significant positive correlations between DGT-Fe, DGT-Mn, DGT-As and DGT-S indicated that sulfate reduction was the start of As mobilization in sediment in winter. In both the estuary and the coastal area, the easily reducible Fe, Mn and As contents in intertidal sediment were higher than those in the subtidal zone. Combined with the As flux across the sediment-overlying water interface (SWI), these phenomena suggested that As in subtidal sediment diffused into overlying water and that As in overlying water tended to accumulate in the intertidal sediment. The total organic carbon content (TOC) and DGT results in the lower reach, estuary and coastal areas indicated that organic matter is the controlling factor of Fe/Mn reduction, sulfate reduction and As mobilization. The BCR test results showed higher reactive fraction contents of Fe, Mn and As in winter sediment, which threaten the overlying water quality.

11.
Adv Mater ; : e2106996, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34626026

RESUMO

Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironment (TME). Therefore, combination therapy involving additional therapeutics is often necessary and the resulting complication may jeopardize the practical feasibility. Herein, an unprecedented "all-in-one" Fe3 O4 /Ag/Bi2 MoO6 nanoparticle (FAB NP) is rationally devised to achieve synergistic chemodynamic, photodynamic, photothermal therapy with guidance by magnetic resonance, photoacoustic, and photothermal imaging. Based on its manifold nanozyme activities (mimicking peroxidase, catalase, superoxide dismutase, glutathione oxidase) and photodynamic property, cascaded nanocatalytic reactions are enabled and sustained in TME for outstanding therapeutic outcomes. The working mechanisms underlying the intraparticulate interactions, sustainability, and self-replenishment arising from the coupling between the nanocatalytic reactions and nanozyme activities are carefully revealed, providing new insights into the design of novel nanozymes for nanocatalytic therapy with high efficiency, good specificity, and low side effects.

12.
Mediators Inflamm ; 2021: 7785890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602858

RESUMO

Breast cancer is one of the top-ranked cancers for incidence and mortality worldwide. The biggest challenges in breast cancer treatment are metastasis and drug resistance, for which work on molecular evaluation, mechanism studies, and screening of therapeutic targets is ongoing. Factors that lead to inflammatory infiltration and immune system suppression in the tumor microenvironment are potential therapeutic targets. Interleukin-1 is known as a proinflammatory and immunostimulatory cytokine, which plays important roles in inflammatory diseases. Recent studies have shown that interleukin-1 cytokines drive the formation and maintenance of an inflammatory/immunosuppressive microenvironment through complex intercellular signal crosstalk and tight intracellular signal transduction, which were found to be potentially involved in the mechanism of metastasis and drug resistance of breast cancer. Some preclinical and clinical treatments or interventions to block the interleukin-1/interleukin-1 receptor system and its up- and downstream signaling cascades have also been proven effective. This study provides an overview of IL-1-mediated signal communication in breast cancer and discusses the potential of IL-1 as a therapeutic target especially for metastatic breast cancer and combination therapy and current problems, aiming at enlightening new ideas in the study of inflammatory cytokines and immune networks in the tumor microenvironment.

13.
CNS Neurosci Ther ; 27(12): 1483-1492, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34605602

RESUMO

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

14.
PLoS Genet ; 17(10): e1009834, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34644293

RESUMO

Stem cells have the potential to maintain undifferentiated state and differentiate into specialized cell types. Despite numerous progress has been achieved in understanding stem cell self-renewal and differentiation, many fundamental questions remain unanswered. In this study, we identify dRTEL1, the Drosophila homolog of Regulator of Telomere Elongation Helicase 1, as a novel regulator of male germline stem cells (GSCs). Our genome-wide transcriptome analysis and ChIP-Seq results suggest that dRTEL1 affects a set of candidate genes required for GSC maintenance, likely independent of its role in DNA repair. Furthermore, dRTEL1 prevents DNA damage-induced checkpoint activation in GSCs. Finally, dRTEL1 functions to sustain Stat92E protein levels, the key player in GSC maintenance. Together, our findings reveal an intrinsic role of the DNA helicase dRTEL1 in maintaining male GSC and provide insight into the function of dRTEL1.


Assuntos
Proteínas de Drosophila/genética , Drosophila/genética , Células Germinativas/fisiologia , Células-Tronco/fisiologia , Animais , Autorrenovação Celular/genética , DNA Helicases/metabolismo , Reparo do DNA/genética , Feminino , Masculino , Transdução de Sinais/genética , Transcriptoma/genética
15.
Endocr J ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34483150

RESUMO

In the current study, we aimed to study the effect of miR-146a on proliferation and migration in an in vitro diabetic foot ulcer (DFU) model by targeting A-kinase-anchoring protein 12 (AKAP12). An in vitro DFU model was initially established using HaCaT cells derived from human keratinocytes and induced by advanced glycation end products (AGEs). The effects of overexpression of miR-146a on proliferation and migration ability were analysed. The expression levels of miR-146a and AKAP12 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and AKAP12, hypoxia-inducible factor-1α (HIF-1α), Wnt3a and ß-catenin protein levels were measured by western blotting. The cell proliferation ability was measured by MTT, and the migration ability was analysed by a cell scratch assay. The binding between miR-146a and AKAP12 was identified using a luciferase reporter assay. The results demonstrated that AGEs significantly suppressed cell proliferation and migration, while the expression of miR-146a decreased and the expression of AKAP12 increased. A luciferase reporter assay revealed that miR-146a could directly target AKAP12. Overexpression of miR-146a promoted cell proliferation and migration in an in vitro DFU model and also promoted the expression of HIF-1α, Wnt3a and ß-catenin but suppressed the expression of AKAP12. Co-overexpression of miR-146a and AKAP12 reversed the effect of miR-146a on cell proliferation and migration. Our findings revealed that miR-146a directly targeted AKAP12 and promoted cell proliferation and migration in an in vitro DFU model. This study provides a new perspective for the study of miR-146a in the treatment of DFU.

16.
World J Emerg Med ; 12(4): 309-316, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512829

RESUMO

BACKGROUND: Our group previously reported that right-sided vagus nerve stimulation (RVNS) significantly improved outcomes after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). However, whether left-sided vagus nerve stimulation (LVNS) could achieve the same effect as RVNS in CPR outcomes remains unknown. METHODS: A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fibrillation (VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation (ROSC), and their health and behavior were evaluated every 24 hours. RESULTS: Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation (VNS) decreased the serum levels of tumor necrosis factor-alpha (TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with findings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no significant difference in efficacy when comparing the laterality of stimulation. CONCLUSIONS: LVNS may have similar effects as RVNS on improving outcomes after CPR.

17.
Mol Ther Nucleic Acids ; 26: 34-48, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34513292

RESUMO

N6-methyladenosine (m6A) modification plays a critical role in mammalian development. However, the role of m6A in the skeletal muscle development remains largely unknown. Here, we report a global m6A modification pattern of goat skeletal muscle at two key development stages and identified that the m6A modification regulated the expression of the growth arrest and DNA damage-inducible 45B (GADD45B) gene, which is involved in myogenic differentiation. We showed that GADD45B expression increased during myoblast differentiation, whereas the downregulation of GADD45B inhibits myogenic differentiation and mitochondrial biogenesis. Moreover, the expression of GADD45B regulates the expression of myogenic regulatory factors and peroxisome proliferator-activated receptor gamma coactivator 1 alpha by activating the p38 mitogen-activated protein kinase (MAPK) pathway. Conversely, the inactivation of p38 MAPK abolished the GADD45B-mediated myogenic differentiation. Furthermore, we found that the knockdown of fat mass and obesity-associated protein (FTO) increases GADD45B m6A modification and decreases the stability of GADD45B mRNA, which impairs myogenic differentiation. Our results indicate that the FTO-mediated m6A modification in GADD45B mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation.

18.
Front Cell Dev Biol ; 9: 712931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513841

RESUMO

Cancer has been generally defined as a cluster of systematic malignant pathogenesis involving abnormal cell growth. Genetic mutations derived from environmental factors and inherited genetics trigger the initiation and progression of cancers. Although several well-known factors affect cancer, mutation features and rules that affect cancers are relatively unknown due to limited related studies. In this study, a computational investigation on mutation profiles of cancer samples in 27 types was given. These profiles were first analyzed by the Monte Carlo Feature Selection (MCFS) method. A feature list was thus obtained. Then, the incremental feature selection (IFS) method adopted such list to extract essential mutation features related to 27 cancer types, find out 207 mutation rules and construct efficient classifiers. The top 37 mutation features corresponding to different cancer types were discussed. All the qualitatively analyzed gene mutation features contribute to the distinction of different types of cancers, and most of such mutation rules are supported by recent literature. Therefore, our computational investigation could identify potential biomarkers and prediction rules for cancers in the mutation signature level.

19.
Front Cardiovasc Med ; 8: 717536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513956

RESUMO

With the globally increasing prevalence, cardiovascular diseases (CVDs) have become the leading cause of mortality. The transplantation of endothelial progenitor cells (EPCs) holds a great promise due to their potential for vasculogenesis, angiogenesis, and protective cytokine release, whose mechanisms are essential for CVD therapies. In reality, many investigations have attributed the therapeutic effects of EPC transplantation to the secretion of paracrine factors rather than the differentiation function. Of note, previous studies have suggested that EPCs could also release exosomes (diameter range of 30-150 nm), which carry various lipids and proteins and are abundant in microRNAs. The EPC-derived exosomes (EPC-EXs) were reported to act on the heart and blood vessels and were implicated in anti-inflammation, anti-oxidation, anti-apoptosis, the inhibition of endothelial-to-mesenchymal transition (EndMT), and cardiac fibrosis, as well as anti-vascular remodeling and angiogenesis, which were considered as protective effects against CVDs. In this review, we summarize the current knowledge on using EPC-EXs as therapeutic agents and provide a detailed description of their identified mechanisms of action to promote the prognosis of CVDs.

20.
Biol Trace Elem Res ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546491

RESUMO

Manganese (Mn) is a crucial trace element for poultry nutrition, and its deficiency compromises tibial cartilage development, leading to perosis and a higher incidence of slipped tendon. Tibial dyschondroplasia (TD) is a metabolic cartilage disease characterized by disruption of endochondral bone formation, which is closely related to extracellular matrix (ECM) degradation, in which Mn deficiency plays an important role. Previous studies have confirmed the role of matrix metalloproteinases (MMPs) in the pathogenesis of TD, but whether dysregulated ECM degradation and MMP expression profiles in growth plate are involved in Mn deficiency-induced avian TD has not been fully elucidated yet. Thus, this study was conducted to clarify these issues. Firstly, we successfully established TD model induced by Mn deficiency in broiler chicks. Mn deficiency decreased the number of chondrocytes, contents of proteoglycan, and type II collagen in tibial growth plate, demonstrating the tibial growth plate damage with enhanced ECM degradation. Also, Mn deficiency inhibited the Nrf2 signaling pathway and enhanced the protein levels of NLRP3, active caspase-1, and active IL-1ß in tibial growth plate, indicating the oxidative stress and inflammatory response in Mn deficiency-induced TD. Additionally, upregulated expression levels of MMPs (MMP1, 9, and 13) were observed in tibial growth plate of Mn deficiency group. In summary, these findings suggest that Mn deficiency-enhanced ECM degradation is involved in avian TD, which may be correlated with oxidative stress, inflammatory response, and upregulation of MMPs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...