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1.
Mol Cancer ; 21(1): 32, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090469

RESUMO

N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic in recent years. M6A plays multifunctional roles in normal and abnormal biological processes, and its role may vary greatly depending on the position of the m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis, most of which involve the breakdown of the plasma membrane. Based on the implications of m6A methylation on PCD, the regulators and functional roles of m6A methylation were comprehensively studied and reported. In this review, we focus on the high-complexity links between m6A and different types of PCD pathways, which are then closely associated with the initiation, progression and resistance of cancer. Herein, clarifying the relationship between m6A and PCD is of great significance to provide novel strategies for cancer treatment, and has a great potential prospect of clinical application.


Assuntos
Adenosina , Neoplasias , Adenosina/análogos & derivados , Adenosina/metabolismo , Apoptose/genética , Humanos , Metilação , Neoplasias/genética , Neoplasias/metabolismo
2.
Mol Cell Endocrinol ; 544: 111541, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973370

RESUMO

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) accounts for a big portion of non-traumatic ONFH; nevertheless, the pathogenesis has not yet been fully understood. GC-induced endothelial dysfunction might be a major contributor to ONFH progression. The Gene Expression Omnibus (GEO) dataset was analyzed to identify deregulated miRNAs in ONFH; among deregulated miRNAs, the physiological functions of miR-122-5p on ONFH and endothelial dysfunction remain unclear. In the present study, miR-122-5p showed to be under-expressed within GC-induced ONFH femoral head tissues and GC-stimulated bone microvascular endothelial cells (BMECs). In human umbilical vein endothelial cells (HUVECs) and BMECs, GC stimulation significantly repressed cell viability, promoted cell apoptosis and increased the mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IFN-γ. After overexpressing miR-122-5p, GC-induced endothelial injuries were attenuated, as manifested by rescued cell viability, cell migration, and tube formation capacity. Regarding the BMP signaling, GC decreased the protein levels of BMP-2/6/7 and SMAD-1/5/8, whereas miR-122-5p overexpression significantly attenuated the inhibitory effects of GC on these proteins. Online tool and experimental analyses revealed the direct binding between miR-122-5p and GREM2, a specific antagonist of BMP-2. In contrast to miR-122-5p overexpression, GREM2 overexpression aggravated GC-induced endothelial injury; GREM2 silencing partially eliminated the effects of miR-122-5p inhibition on GC-stimulated HUVECs and BMECs. Finally, GREM2 silencing reversed the suppressive effects of GC on BMP-2/6/7 and SMAD-1/5/8, and attenuated the effects of miR-122-5p inhibition on these proteins upon GC stimulation. Conclusively, the present study demonstrates a miR-122-5p/GREM2 axis modulating the GC-induced endothelial damage via the BMP/SMAD signaling. Considering the critical role of endothelial function in ONFH pathogenesis, the in vivo role and clinical application of the miR-122-5p/GREM2 axis is worthy of further investigation.


Assuntos
Glucocorticoides , MicroRNAs , Apoptose , Citocinas/metabolismo , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
3.
Rev. bras. med. esporte ; 28(5): 493-496, Set.-Oct. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376668

RESUMO

ABSTRACT Introduction: The Fifth International Conference on Sports Biochemistry defines sports fatigue as the physiological process of dysfunction at a certain level or inability to maintain predetermined exercise intensity. When left untreated, it can cause adverse effects to the musculoskeletal system. Natural alternatives for controlling sports fatigue exist in Chinese culture, but scientific research is needed to determine the effectiveness of these treatments. Objective: This study aimed to verify the effect of traditional Chinese medicinal baths on athletes' muscle fatigue. Methods: 100 athletes with exercise-induced muscle fatigue were randomly divided into two groups. The control group received ganglioside injection combined with therapeutic exercise protocols, while the experimental group received the medicinal bath based on traditional Chinese medicine. Tonus of adductors, ischiotibials, gastrocnemius, in addition to lower limb motor function, was evaluated. Results: The total effective rate (90.8%) of the observation group was higher than that of the control group (72.3%), and the difference was statistically significant (P<0.05). After treatment, adductor, hamstring, and gastrocnemius muscle tension in the observation group were lower than the control group (P<0.05). Gross motor function assessment score (GMFM-88), Berg Balance Scale (BBS), 10m walking speed on a 20cm wide walkway (MWS) in the observation group were higher than those in the control group (P<0.05). Conclusion: Chinese herbal lavender lotion combined with suspension exercise can effectively improve the body's muscle strength after exercises, accelerate the recovery of muscle strength, and significantly reduce exercise-induced muscle fatigue. Evidence Level II; Therapeutic Studies - Investigating the result.


RESUMO Introdução: A Quinta Conferência Internacional de Bioquímica Esportiva, define a fadiga esportiva como o processo fisiológico de disfunção em um determinado nível ou incapacidade de manter uma intensidade de exercício predeterminada. Quando não tratada, pode causar efeitos adversos ao sistema musculoesquelético. Há alternativas naturais para o controle da fadiga esportiva na cultura chinesa, mas pesquisas científicas são necessárias afim de descobrir a real efetividade desses tratamentos. Objetivo: Verificar o efeito do banho medicinal tradicional da medicina chinesa na fadiga muscular de atletas. Métodos: 100 atletas com fadiga muscular induzida por exercícios foram aleatoriamente divididos em dois grupos. O grupo controle recebeu injeção de gangliosideo combinada com protocolos de exercícios terapêuticos enquanto o grupo experimental recebeu o banho medicinal baseado na medicina tradicional chinesa. Foi avaliado o tônus de adutores, isquiotibiais, gastrocnêmios além da função motora dos membros inferiores. Resultados: A taxa efetiva total (90,8%) do grupo de observação foi superior à do grupo controle (72,3%) e a diferença foi estatisticamente significante (P<0,05). Após o tratamento, a tensão muscular adutores, jarrete e gastrocnêmio no grupo de observação foi menor que o grupo controle (P<0,05). O escore bruto de avaliação da função motora (GMFM-88), escore de escala de balanço de Berg (BBS), velocidade de caminhada de 10m em uma passarela de 20cm de largura (MWS) no grupo de observação foram maiores do que os do grupo controle (P<0,05). Conclusão: A loção de lavanda de ervas chinesas combinada com o exercício de suspensão pode melhorar efetivamente a força muscular do corpo após os exercícios, acelerar a recuperação da força muscular e reduzir significativamente a fadiga muscular induzida pelo exercício. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.


RESUMEN Introducción: La Quinta Conferencia Internacional de Bioquímica del Deporte, define la fatiga deportiva como el proceso fisiológico de disfunción a un determinado nivel o incapacidad para mantener una intensidad de ejercicio predeterminada. Si no se trata, puede causar efectos adversos en el sistema musculoesquelético. Existen alternativas naturales para el control de la fatiga deportiva en la cultura china, pero se necesita una investigación científica para descubrir la eficacia real de estos tratamientos. Objetivo: Verificar el efecto del baño medicinal tradicional de la medicina china sobre la fatiga muscular de los atletas. Métodos: 100 atletas con fatiga muscular inducida por el ejercicio fueron divididos aleatoriamente en dos grupos. El grupo de control recibió una inyección de gangliósidos combinada con protocolos de ejercicio terapéutico, mientras que el grupo experimental recibió el baño medicinal basado en la medicina tradicional china. Se evaluó el tono de los aductores, los isquiotibiales y los gastrocnemios, además de la función motora de los miembros inferiores. Resultados: La tasa efectiva total (90,8%) del grupo de observación fue superior a la del grupo de control (72,3%) y la diferencia fue estadísticamente significativa (P<0,05). Tras el tratamiento, la tensión de los músculos aductores, jarretes y gastrocnemios en el grupo de observación fue inferior a la del grupo de control (P<0,05). La puntuación de la evaluación de la función motora gruesa (GMFM-88), la puntuación de la Escala de Equilibrio de Berg (BBS) y la velocidad de marcha de 10 m en una pasarela de 20 cm de ancho (MWS) en el grupo de observación fueron mayores que las del grupo de control (P<0,05). Conclusión: La loción de hierbas chinas de lavanda combinada con el ejercicio de suspensión puede mejorar eficazmente la fuerza muscular del cuerpo después de los ejercicios, acelerar la recuperación de la fuerza muscular y reducir significativamente la fatiga muscular inducida por el ejercicio. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

4.
Front Physiol ; 13: 902802, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910570

RESUMO

The objective was to investigate the effects of alfalfa (Medicago sativa Linn)-mixed silage fermentation material (AMSFM) on various aspects of growth, function, and carcass characteristics of Lande (meat) geese. Based on a previous study, we used the following AMSFM: 80% Alfalfa +10% soybean meal +10% DDGS ensiled for 45 days. Lande geese, n = 264, 77 days of age, were randomly allocated into four groups with six replicates in each group. Control geese were fed a basal diet, whereas experimental groups were fed a basal diet supplemented with 6, 12, or 24% AMSFM. The experiment lasted 21 days. The AMSFM promoted some aspects of growth, with increase (p < 0.05) in leg muscle rate, lean meat rate, muscle protein content, and total energy content of leg muscle plus concurrent decreases (p < 0.05) in crude fat content and abdominal fat rate in chest muscle. In addition, AMSFM increased (p < 0.05) glutathione content in chest and leg muscles and serum superoxide dismutase activity, and it reduced (p < 0.05) muscle malondialdehyde content and serum concentrations of triglycerides, total cholesterol, urea, and aspartate aminotransferase, consistent with good liver and kidney function. Moreover, AMSFM improved (p < 0.05) ileum morphology. In conclusion, the optimal supplemented rate of AMSFM in the meat geese diet (12%) improved immunity and antioxidant status and enhanced growth performance and carcass characteristics of meat geese.

5.
Drug Des Devel Ther ; 16: 2365-2382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910781

RESUMO

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.


Assuntos
Adenocarcinoma de Pulmão , Curcumina , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais , Biologia Computacional , Curcumina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Simulação de Acoplamento Molecular
6.
Theranostics ; 12(12): 5364-5388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910787

RESUMO

Autophagy is a catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, thus serving an important role in cellular homeostasis and protection against insults. We previously reported that defects in autophagy contribute to neuronal cell damage in traumatic spinal cord injury (SCI). Recent data from other inflammatory models implicate autophagy in regulation of immune and inflammatory responses, with low levels of autophagic flux associated with pro-inflammatory phenotypes. In the present study, we examined the effects of genetically or pharmacologically manipulating autophagy on posttraumatic neuroinflammation and motor function after SCI in mice. Methods: Young adult male C57BL/6, CX3CR1-GFP, autophagy hypomorph Becn1+/- mice, and their wildtype (WT) littermates were subjected to moderate thoracic spinal cord contusion. Neuroinflammation and autophagic flux in the injured spinal cord were assessed using flow cytometry, immunohistochemistry, and NanoString gene expression analysis. Motor function was evaluated with the Basso Mouse Scale and horizontal ladder test. Lesion volume and spared white matter were evaluated by unbiased stereology. To stimulate autophagy, disaccharide trehalose, or sucrose control, was administered in the drinking water immediately after injury and for up to 6 weeks after SCI. Results: Flow cytometry demonstrated dysregulation of autophagic function in both microglia and infiltrating myeloid cells from the injured spinal cord at 3 days post-injury. Transgenic CX3CR1-GFP mice revealed increased autophagosome formation and inhibition of autophagic flux specifically in activated microglia/macrophages. NanoString analysis using the neuroinflammation panel demonstrated increased expression of proinflammatory genes and decreased expression of genes related to neuroprotection in Becn1+/- mice as compared to WT controls at 3 days post-SCI. These findings were further validated by qPCR, wherein we observed significantly higher expression of proinflammatory cytokines. Western blot analysis confirmed higher protein expression of the microglia/macrophage marker IBA-1, inflammasome marker, NLRP3, and innate immune response markers cGAS and STING in Becn1+/- mice at 3 day after SCI. Flow cytometry demonstrated that autophagy deficit did not affect either microglial or myeloid counts at 3 days post-injury, instead resulting in increased microglial production of proinflammatory cytokines. Finally, locomotor function showed significantly worse impairments in Becn1+/- mice up to 6 weeks after SCI, which was accompanied by worsening tissue damage. Conversely, treatment with a naturally occurring autophagy inducer trehalose, reduced protein levels of p62, an adaptor protein targeting cargo to autophagosomes as well as the NLRP3, STING, and IBA-1 at 3 days post-injury. Six weeks of trehalose treatment after SCI led to improved motor function recovery as compared to control group, which was accompanied by reduced tissue damage. Conclusions: Our data indicate that inhibition of autophagy after SCI potentiates pro-inflammatory activation in microglia and is associated with worse functional outcomes. Conversely, increasing autophagy with trehalose, decreased inflammation and improved outcomes. These findings highlight the importance of autophagy in spinal cord microglia and its role in secondary injury after SCI.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Traumatismos da Medula Espinal , Animais , Autofagia , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal/complicações , Trealose/metabolismo , Trealose/farmacologia
7.
Oxid Med Cell Longev ; 2022: 7411824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910849

RESUMO

Salvianolic acid A (SAA) is one of bioactive polyphenol extracted from a Salvia miltiorrhiza (Danshen), which was widely used to treat cardiovascular disease in traditional Chinese medicine. SAA has been reported to be protective in cardiovascular disease and ischemia injury, with anti-inflammatory and antioxidative effect, but its role in acute lung injury (ALI) is still unknown. In this study, we sought to investigate the therapeutic effects of SAA in a murine model of lipopolysaccharide- (LPS-) induced ALI. The optimal dose of SAA was determined by comparing the attenuation of lung injury score after administration of SAA at three different doses (low, 5 mg/kg; medium, 10 mg/kg; and, high 15 mg/kg). Dexamethasone (DEX) was used as a positive control for SAA. Here, we showed that the therapeutic effect of SAA (10 mg/kg) against LPS-induced pathologic injury in the lungs was comparable to DEX. SAA and DEX attenuated the increased W/D ratio and the protein level, counts of total cells and neutrophils, and cytokine levels in the BALF of ALI mice similarly. The oxidative stress was also relieved by SAA and DEX according to the superoxide dismutase and malondialdehyde. NET level in the lungs was elevated in the injured lung while SAA and DEX reduced it significantly. LPS induced phosphorylation of Src, Raf, MEK, and ERK in the lungs, which was inhibited by SAA and DEX. NET level and phosphorylation level of Src/Raf/MEK/ERK pathway in the neutrophils from acute respiratory distress syndrome (ARDS) patients were also inhibited by SAA and DEX in vitro, but the YEEI peptide reversed the protective effect of SAA completely. The inhibition of NET release by SAA was also reversed by YEEI peptide in LPS-challenged neutrophils from healthy volunteers. Our data demonstrated that SAA ameliorated ALI via attenuating inflammation, oxidative stress, and neutrophil NETosis. The mechanism of such protective effect might involve the inhibition of Src activation.


Assuntos
Lesão Pulmonar Aguda , Doenças Cardiovasculares , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Ácidos Cafeicos , Doenças Cardiovasculares/patologia , Humanos , Lactatos , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno , Neutrófilos/metabolismo
8.
Front Cardiovasc Med ; 9: 952114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911512

RESUMO

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/ß cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting against pressure overload. Interestingly, the cardioprotective effect of SR9009 against TAC retains in cDKO mice. In addition, SR9009 administered at the time points corresponding to the peak or trough of REV-ERB expression showed similar cardioprotective effects, suggesting the REV-ERB-independent mechanisms in SR9009-mediated post-TAC cardioprotection. These findings highlight that genetic deletion of REV-ERB in cardiomyocytes accelerates adverse cardiac remodeling in response to pressure overload and demonstrated the REV-ERB-independent cardioprotective effect of SR9009 upon pressure overload.

9.
Front Oncol ; 12: 914997, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912198

RESUMO

Background: Numerous studies showed that preoperative platelet-albumin-bilirubin (PALBI) grade was closely related to the prognostic outcome of patients with hepatocellular carcinoma (HCC). However, the conclusions were inconsistent. Therefore, we implemented the study to comprehensively evaluate the association between PALBI grade and prognosis in patients with HCC. Methods: Relevant articles were collected from the specified databases until February 10, 2022. We included all studies exploring the relationship between PALBI grade and prognosis in HCC patients. We used the hazard ratio (HR) and 95% confidence interval (CI) to calculate the comprehensive analysis. All data analyses were performed using STATA 12.0. Results: Thirteen retrospective articles containing 15534 patients were included in the meta-analysis. The pooled results displayed that the high PALBI grade was obviously correlated with poor overall survival (OS) (HR: 1.71, 95% CI: 1.46-2.02) and disease-free survival/relapse-free survival (DFS/RFS) (HR:1.31; 95% CI: 1.11-1.54). Subgroup analyses further confirmed the reliability of the comprehensive results. Conclusions: PALBI may be a valid prognostic indicator in HCC patients. More investigations were needed to test our findings.

10.
Front Oncol ; 12: 931812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912248

RESUMO

Background: Lung cancer is the most common primary tumor metastasizing to the brain. A significant proportion of lung cancer patients show epidermal growth factor receptor (EGFR) mutation status discordance between the primary cancer and the corresponding brain metastases, which can affect prognosis and therapeutic decision-making. However, it is not always feasible to obtain brain metastases samples. The aim of this study was to establish a radiomic model to predict the EGFR mutation status of lung cancer brain metastases. Methods: Data from 162 patients with resected brain metastases originating from lung cancer (70 with mutant EGFR, 92 with wild-type EGFR) were retrospectively analyzed. Radiomic features were extracted using preoperative brain magnetic resonance (MR) images (contrast-enhanced T1-weighted imaging, T1CE; T2-weighted imaging, T2WI; T2 fluid-attenuated inversion recovery, T2 FLAIR; and combinations of these sequences), to establish machine learning-based models for predicting the EGFR status of excised brain metastases (108 metastases for training and 54 metastases for testing). The least absolute shrinkage selection operator was used to select informative features; radiomics models were built with logistic regression of the training cohort, and model performance was evaluated using an independent test set. Results: The best-performing model was a combination of 10 features selected from multiple sequences (two from T1CE, five from T2WI, and three from T2 FLAIR) in both the training and test sets, resulting in classification area under the curve, accuracy, sensitivity, and specificity values of 0.85 and 0.81, 77.8% and 75.9%, 83.7% and 73.1%, and 73.8% and 78.6%, respectively. Conclusions: Radiomic signatures integrating multi-sequence MR images have the potential to noninvasively predict the EGFR mutation status of lung cancer brain metastases.

11.
Thromb J ; 20(1): 43, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915486

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in general thoracic surgery, but the incidence of patients undergoing surgery for bronchiectasis was not known. The purpose of our study was to investigate the incidence of VTE in bronchiectasis patients undergoing lung resection and to evaluate the risk stratification effect of the modified caprini risk assessment model (RAM). METHODS: We prospectively enrolled patients with bronchiectasis who underwent lung resection surgery between July 2016 and July 2020.The postoperative duplex lower-extremity ultrasonography or(and) computed tomographic pulmonary angiography (CTPA) was performed to detect VTE. The clinical characteristics and caprini scores of VTE patients and non-VTE patients would be compared and analyzed. Univariate logistic regression was performed to evaluate whether higher Caprini scores were associated with postoperative VTE risk.In addition, We explored the optimal cutoff for caprini score in patients with bronchiectasis by using the receiver operating characteristic (ROC) curve. RESULTS: One hundred and seventeen patients were eligible based on the prospective study criteria. The postoperative VTE incidence was 8.5% (10/117). By comparing the clinical characteristics and Caprini scores of VTE and non-VTE patients, the median preoperative hospitalization (7 vs 5 days, P = 0.028) and Caprini score (6.5 vs 3,P < 0.001) were significantly higher in VTE patients. In univariate logistic regression, a higher Caprini score was associated with higher odds ratio (OR) for VTE of 1.7, 95% confidence interval (CI) was from 1.2 to 2.5 (P = 0.001), C-statistics was 0.815 in the modified caprini RAM for predicting VTE. In a multivariable analysis adjusting for preoperative hospitalization, a higher Caprini score was associated with higher odds OR for VTE of 1.8 (95%CI: 1.2-2.6, P = 0.002), C-statistics was 0.893 in the caprini RAM for predicting VTE. When taking the Caprini score as 5 points as the diagnostic threshold, the Youden index is the largest. CONCLUSIONS: The postoperative VTE incidence in patients undergoing lung resection for bronchiectasis was 8.5%.The modified caprini RAM effectively stratified bronchiectasis surgery patients for risk of VTE and showed excellent predictive power for VTE. The patients with postoperative caprini scores = 5, should be recommended to take positive measures to prevent postoperative VTE. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR-EOC-17010577.

12.
RSC Adv ; 12(32): 20771-20777, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35919178

RESUMO

A chemical investigation on the herb Gerbera anandria (Linn) Sch-Bip led to the isolation and identification of six previously undescribed coumarin derivatives, named Gerberdriasins A-F (1-6). Structurally, their chemical structures and absolute configurations were determined by nuclear magnetic resonance (1D and 2D NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), experimental and quantum mechanical nuclear magnetic resonance (QM-NMR) methods, Mosher's method and calculated electronic circular dichroism (ECD) experiments. The biological activity of the obtained compounds showed that they displayed significant neuroprotective effects against scopolamine-induced injury in PC12 cells at the concentrations 12.5, 25.0 and 50.0 nM. Further study demonstrated that 1 could inhibit cell apoptosis, decrease malondialdehyde (MDA) levels and increase superoxide dismutase (SOD) activity in scopolamine-treated PC12 cells.

13.
Diabetes Metab Syndr Obes ; 15: 2183-2195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923253

RESUMO

Purpose: To explore the mechanism of Yishen capsule against diabetic nephropathy (DN) based on the analysis of transcriptomics. Material and Methods: SD rats (Male, SPF grade) were randomly divided into four groups, the normal group, the DN group, the Yishen capsule group and the resveratrol group. Urine and renal tissue samples were collected after feeding with physiological saline and above drugs for 8 weeks. 24-hour urine microalbumin protein was detected by ELISA. HE staining and PAS staining were performed on renal tissues. Differential gene expression in renal tissues was analyzed by transcriptome sequencing. The differentially expressed genes were analyzed by GO enrichment and KEGG enrichment, and verified by RT-PCR and immunohistochemistry staining. Results: The level of 24-hour urinary microalbumin in DN group was increased, while Yishen capsule treatment reversed the increasement of urinary microalbumin. Mesangial cell proliferation, matrix accumulation, edema and vacuolar degeneration of renal tubular epithelial cells and glycogen accumulation were observed in DN group. However, pathological phenotypes mentioned above were alleviated after Yisen capsule administration. This result indicates that Yishen capsule reversed pathological phenotypes of DN in rats. The expression of 261 genes were changed in Yishen capsule group compared with DN group. GO enrichment analysis and KEGG pathway analysis showed that these genes were implicated in pathways, including mineral absorption, adipocytokine signaling pathway, fatty acid biosynthesis, thyroid hormone synthesis, renin-angiotensin system, and NOD-like receptor signaling pathway. Based on previous reported study, the expression of key factors in NOD-like receptor signaling pathway was verified. RT-PCR and immunohistochemistry staining showed that the expression of NLRP3, Caspase-1 and IL-1ß in renal tissues of DN group were increased (P < 0.05), which were decreased in Yishen capsule group (P < 0.05). Conclusion: Yishen capsule reduced microalbuminuria and alleviated pathological changes in DN rats, which may be achieved by regulating NOD-like receptor signaling pathway.

14.
Ther Adv Chronic Dis ; 13: 20406223221091177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924009

RESUMO

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes, Firmicutes, Bacteroidetes, etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism.

15.
Front Psychiatry ; 13: 969166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923446

RESUMO

[This corrects the article DOI: 10.3389/fpsyt.2021.802513.].

16.
J Clin Invest ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35925681

RESUMO

Infantile (fetal and neonatal) megakaryocytes have a distinct phenotype consisting of hyperproliferation, limited morphogenesis, and low platelet production capacity. These properties contribute to clinical problems that include thrombocytopenia in neonates, delayed platelet engraftment in recipients of cord blood stem cell transplants, and inefficient ex vivo platelet production from pluripotent stem cell-derived megakaryocytes. The infantile phenotype results from deficiency of the actin-regulated coactivator, MKL1, which programs cytoskeletal changes driving morphogenesis. As a strategy to complement this molecular defect, we screened pathways with potential to affect MKL1 function and found that Dyrk1a kinase inhibition dramatically enhanced megakaryocyte morphogenesis in vitro and in vivo. Dyrk1 inhibitors rescued enlargement, polyploidization, and thrombopoiesis in human neonatal megakaryocytes. Megakaryocytes derived from induced pluripotent stem cells responded in a similar manner. Progenitors undergoing Dyrk1 inhibition demonstrated filamentous actin assembly, MKL1 nuclear translocation, and modulation of MKL1 target genes. Loss of function studies confirmed MKL1 involvement in this morphogenetic pathway. Ablim2, a stabilizer of filamentous actin, increased with Dyrk1 inhibition, and Ablim2 knockdown abrogated the actin, MKL1, and morphogenetic responses to Dyrk1 inhibition. These results thus delineate a pharmacologically tractable morphogenetic pathway whose manipulation may alleviate clinical problems associated with the limited thrombopoietic capacity of infantile megakaryocytes.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35925873

RESUMO

Ovarian cancer has become an urgent threat to global female healthcare. Cisplatin, as the traditional chemotherapeutic agent against ovarian cancer, retains several limitations, such as drug resistance and dose-limiting toxicity. In order to solve the above problems and promote the therapeutic effect of chemotherapy, combining chemotherapy and phototherapy has aroused wide interest. In this study, we constructed a versatile cisplatin prodrug-conjugated therapeutic platform based on ultrasmall CuS-modified Fe(III)-metal-organic frameworks (MIL-88) (named M-Pt/PEG-CuS) for tumor-specific enhanced synergistic chemo-/phototherapy. After intravenous injection, M-Pt/PEG-CuS presented obvious accumulation in tumor and Fe(III)-MOFs possessed magnetic resonance imaging (MRI) to guide synergy therapy. Both in vitro and in vivo experimental results showed that M-Pt/PEG-CuS could not only successfully inhibit tumor growth by combining chemotherapy and NIR-II PTT but also avoid the generation of liver damage by the direct treatment of cisplatin(II). Our work presented the development of the nanoplatform as a novel NIR-II photothermal agent, as well as gave a unique combined chemo-photothermal therapy strategy, which might provide new ways of ovarian cancer therapy for clinical translation.

18.
Acta Crystallogr D Struct Biol ; 78(Pt 8): 997-1009, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916224

RESUMO

Protein crystals grown in microfluidic droplets have been shown to be an effective and robust platform for storage, transport and serial crystallography data collection with a minimal impact on diffraction quality. Single macromolecular microcrystals grown in nanolitre-sized droplets allow the very efficient use of protein samples and can produce large quantities of high-quality samples for data collection. However, there are challenges not only in growing crystals in microfluidic droplets, but also in delivering the droplets into X-ray beams, including the physical arrangement, beamline and timing constraints and ease of use. Here, the crystallization of two human gut microbial hydrolases in microfluidic droplets is described: a sample-transport and data-collection approach that is inexpensive, is convenient, requires small amounts of protein and is forgiving. It is shown that crystals can be grown in 50-500 pl droplets when the crystallization conditions are compatible with the droplet environment. Local and remote data-collection methods are described and it is shown that crystals grown in microfluidics droplets and housed as an emulsion in an Eppendorf tube can be shipped from the US to the UK using a FedEx envelope, and data can be collected successfully. Details of how crystals were delivered to the X-ray beam by depositing an emulsion of droplets onto a silicon fixed-target serial device are provided. After three months of storage at 4°C, the crystals endured and diffracted well, showing only a slight decrease in diffracting power, demonstrating a suitable way to grow crystals, and to store and collect the droplets with crystals for data collection. This sample-delivery and data-collection strategy allows crystal droplets to be shipped and set aside until beamtime is available.


Assuntos
Microfluídica , Proteínas , Cristalização , Cristalografia por Raios X , Coleta de Dados , Emulsões , Humanos
19.
20.
Langmuir ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921226

RESUMO

Dynamic wetting, described by a dynamic contact angle (DCA), is a fundamental behavior of fluid on surface. With the development of blue energy, the research of droplet nanogenerator is flourishing. There is a growing interest in the dynamic wetting behavior of nanodroplets on surfaces. Molecular dynamics simulations are performed to reveal the influence of the velocity of nanodroplets and the wetting state (Cassie and Wenzel) on the DCA and the energy dissipation on the contact line. The simulation results demonstrate a more complicated scenario of dynamic wetting than the static wetting: The increasing rate of advancing DCA is lower than the decreasing rate of the receding DCA with respect to the nanodroplet velocity. As for the Wenzel state, larger surface roughness increases the dynamic wetting hysteresis, while for Cassie nanodroplets, the larger surface roughness leads to smaller dynamic wetting hysteresis. It is found that a structural force exists on the rough surface. The energy dissipation of the dynamic wetting mainly comes from the motion of the contact line, which is positively correlated to the velocity and can be decomposed to the viscosity and friction dissipations, respectively. The Cassie state causes much lower energy dissipation than the Wenzel state. Furthermore, the quasi-static contact angle is proposed to describe the contact angle on a rough surface. These findings advance the understanding of dynamic wetting behavior and inspire theoretical guidance for the design of novel functional interfaces.

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