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1.
Sci Total Environ ; 804: 150235, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798749

RESUMO

The nitrate reduction contributions of denitrification, anaerobic ammonium oxidation (anammox) and dissimilatory nitrate reduction to ammonium (DNRA) remain largely unknown especially in the context of river remediation. In this research, the quantitative differentiation of these three nitrate-reduction processes with different remediation conditions was done by the joint use of microbial analysis and nitrogen isotope-tracing. The experiments were done in simulated river systems with 100-day operations. The results of isotope-tracing showed that the respective N-removal contribution of denitrification was 85.88%-92.46% and 83.49%-84.73% in urban river with aeration and addition of Ca(NO3)2, whereas anammox became the same important (contribution of 49.35%-57.85%) with denitrification for nitrogen removal at a high C/N (Chemical oxygen demand/total nitrogen) ratio of 20. Besides, DNRA only occurred at a C/N ratio of 10 with high-level ammonium accumulation (11.20 ± 0.61 mg/L). Microbial analyses indicated that Ca(NO3)2 injection could promote not only the relative abundance of Proteobacteria (from 47.66% to 59.52%) but also the abundance of hzsB (from (4.66 ± 0.40) × 104 copies·g-1 to (2.66 ± 0.12) × 105 copies·g-1). Moreover, Ca(NO3)2 injection showed significantly positive correlation with Candidatus Jettenia of hzsB and Thiobacillus of all the denitrification functional genes including narG, norB, nosZ and nirS. The C/N ratio showed significantly positive correlation with Azoarcus of nirS (r = 0.941, p < 0.01) and Alloactinosynnema of hzsB (r = 0.941, p < 0.01). It was worth noting that Thiobacillus dominated in N-transformation processes, which underlined the need for the coupling of N transformation with other elements such as sulfur for better understanding and manipulating N cycling in urban rivers.


Assuntos
Compostos de Amônio , Desnitrificação , Variação Genética , Nitratos/análise , Nitrogênio , Oxirredução , Rios
2.
Reprod Domest Anim ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850471

RESUMO

Postpartum ovarian cycle arrest is the main factor affecting yak reproductive efficiency. There are few reports regarding the molecular regulatory mechanism of postpartum estrus at transcriptome and proteome level in yaks. Our previous studies focused on the ovaries of yaks with postpartum ovarian cycle arrest and postpartum estrus yaks. In this study, RNA sequencing transcriptomic study was combined with quantitative proteomic analyses to identify postpartum ovarian cycle-related genes and proteins. Consequently 1,149 genes and 24 proteins were found to be up- or downregulated during postpartum estrus. The analysis of differentially regulated genes identified three gene or protein pairs that were synchronously upregulated and no gene or protein pairs that were synchronously downregulated, suggesting that these upregulated genes may regulate the postpartum ovarian cycle. The functional classification of these differentially expressed genes and proteins indicated their connection with oocyte meiosis, the estrogen signaling pathway, progesterone-mediated oocyte maturation and the gonadotrophin releasing hormone (GnRH) signaling pathway. In this study, a total of six genes and two proteins involved in the oocyte meiosis, the estrogen signaling pathway, progesterone-mediated oocyte maturation and the GnRH signaling pathway were identified. The CSNK1A1, M91_09723, M91_11326, M91_21439, M91_19073, SHC2, Atf6b, M91_03062, HSPCA and calmodulin could regulate estrus, respectively, in the postpartum so as to control the anestrus status.

3.
Scand J Gastroenterol ; : 1-10, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726133

RESUMO

BACKGROUND: The present study aimed to assess the survival, incidence, and characteristics of secondary primary lung cancer (SPLC) after esophageal cancer (EC-LC). METHODS: The patients with esophageal cancer (EC) who developed SPLC and patients with first primary lung cancer (LC-1) were retrospectively reviewed in the Surveillance, Epidemiology, and End Results 18 registries covering 2000-2016. Overall survival and characteristics were compared between patients with EC-LC and patients with LC-1. The independent relation between a history of EC and death was evaluated by calculating hazard ratios in multivariate Cox regression analysis propensity score-matching analysis, and multiple imputation for cases with missing information. RESULTS: In comparison with the general population, the patients with EC had a higher risk for developing secondary primary lung cancer (SIR =1.86, 95% confidence interval (CI): 1.69-2.05). A history of EC was found to be an independent risk factor of death for lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients in localized stage based on multivariate Cox regression analysis, propensity score-matching analysis and multiple imputation. CONCLUSIONS: There is a significantly increased risk of secondary primary lung cancer in EC survivors and a history of EC adversely affects overall survival in individuals who subsequently develop localized LUSC and LUAD. Clinicians should moderately strengthen lung tissue protection during the management of EC patients.

4.
J Healthc Eng ; 2021: 9457070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840706

RESUMO

Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors α-globulin, γ-globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of α-globulin, γ-globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.

6.
Front Aging Neurosci ; 13: 703734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512306

RESUMO

Background: Multimodal CT, including CT angiography (CTA) and CT perfusion (CTP), was increasingly used in stroke triage. This study was to determine the relationship between a new integrated parameter-both collateral circulation and relative permeability surface (PS)-and the hemorrhagic transformation (HT) in acute ischemic stroke (AIS) with middle cerebral artery occlusion (MCAO). Methods: We retrospectively reviewed consecutive AIS patients with MCAO who underwent baseline CTA/CTP within 4 h of symptom onset and follow-up susceptibility-weighted imaging (SWI) within 3 weeks. Collateral circulation was assessed on the baseline CTA. Baseline CTP data were postprocessed to generate PS parameter. The patients with poor collateral circulation and at the same time with high relative PS were classified as the group of both poor collateral circulation and high relative PS. HT was defined according to European Cooperative Acute Stroke Study II criteria on follow-up SWI imaging. Multivariate logistic regression analysis was performed using HT as an outcome variable. Results: The group of patients with both poor collateral circulation and high relative PS was thirteen and thirty-three (52%) developed HT of the final cohort sixty-three AIS patients with MCAO. Multivariate logistic analysis revealed the new integrated parameter-both collateral circulation and relative PS (odds ratio, 16.59; 95% confidence interval, 13.09-19.10; P < 0.001) was independent predictor of HT. The area under the curve was 0.85 (95% confidence interval, 0.81-0.89). The sensitivity was 57%, specificity 97% and positive predictive value 92%, negative predictive value 58%. Conclusions: For AIS patients with MCAO, these with poor collateral circulation on CTA and at the same time with high relative PS on CTP were at high risk for HT.

7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 967-972, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590565

RESUMO

OBJECTIVE: To establish a nomogram model for predicting the risk of coronary artery disease in elderly patients with acute myocardial infarction (AMI). METHODS: The clinical data of elderly patients with AMI who underwent coronary angiography in the department of cardiology of Cangzhou Central Hospital from July 2015 to March 2020 were analyzed, including age, gender, smoking history, underlying diseases, family history, blood pressure, left ventricular ejection fraction (LVEF), and several biochemical indicators at admission, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein [Lp(a)], apolipoproteins (ApoA, ApoB), ApoA/B ratio, total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), fasting blood glucose (FBG) and uric acid (UA). Patients were divided into model group (2 484 cases) and validation group (683 cases) according to the ratio of 8:2. According to Gensini score, the model group and validation group were divided into mild lesion group (0-20 points) and severe lesion group (≥ 81 points). The differences of each index between different coronary lesion degree groups were compared. Lasso regression and Logistic regression were used to analyze the risk factors of aggravating coronary lesion risk in elderly patients with AMI, and then the nomogram prediction model was established for evaluation and external validation. RESULTS: (1) In the model group, there were significant differences in the family history of coronary heart disease, FBG and HDL-C between the mild lesion group (411 cases) and the severe lesion group (417 cases) [family history of coronary heart disease: 3.6% vs. 7.7%, FBG (mmol/L): 5.88±1.74 vs. 6.43±2.06, HDL-C (mmol/L): 1.48±0.69 vs. 1.28±0.28, all P < 0.05]. In the validation group, there were significant differences between the mild lesion group (153 cases) and the severe lesion group [132 cases; FBG (mmol/L): 5.58±0.88 vs. 6.85±0.79, HDL-C (mmol/L): 1.59±0.32 vs. 1.16±0.21, both P < 0.05]. (2) Lasso regression analysis showed that family history of coronary heart disease, FBG, and HDL-C were risk factors of coronary artery disease in elderly patients with AMI, with coefficients 0.118, 0.767, and -0.558, respectively. Logistic regression analysis showed that FBG [odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.051-2.082, P = 0.025] and HDL-C (OR = 0.386, 95%CI was 0.270-0.553, P < 0.001] were independent risk factors of coronary artery disease in elderly patients with AMI. (3) According to the rank score of FBG and HDL-C, the nomogram prediction risk model of aggravating coronary artery disease degree was established for each patient. It was concluded that the risk of coronary artery disease in elderly people with higher FBG level and (or) lower HDL-C level was significantly increased. (4) The nomogram model constructed with the model group data predicted the risk concordance index (C-index) was 0.689, and the C-index of the external validation group was 0.709. CONCLUSIONS: FBG and HDL-C are independent risk factors for aggravating coronary artery disease in elderly patients with AMI. The nomogram model of aggravating coronary artery disease in elderly patients with AMI has good predictive ability, which can provide more intuitive research methods and clinical value for preventing the aggravation of coronary artery disease in elderly patients.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Idoso , HDL-Colesterol , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Nomogramas , Fatores de Risco , Volume Sistólico , Função Ventricular Esquerda
8.
Bioresour Technol ; 341: 125822, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34467889

RESUMO

This study discovered one nitrate-calcium-based anammox start-up pathway. Compared with control, the start-up time of anammox was saved by 33.3%, and the average total nitrogen removal efficiency increased from 29.6% to 53.7% during the start-up. Besides, the continuous nitrite accumulation (1.18 mg/L) and a marked increase in the relative abundance of denitrifying and anammox bacteria were observed in the only Ca(NO3)2-added group. These results suggested that calcium nitrate induced partial denitrification to provide nitrite for anammox. Additionally, the role of dissimilatory nitrate reduction to ammonium (DNRA) in the Ca(NO3)2-added systems also deserved attention, for the contribution of DNRA to nitrate removal as well as the relative abundance of DNRA bacteria were both increased for the Ca(NO3)2-added groups. These results suggested that a mutualistic symbiosis among denitrification, DNRA and anammox exists in the calcium nitrate-added systems, which may explain the reason for acceleration of anammox start-up by adding calcium nitrate.


Assuntos
Compostos de Amônio , Anaerobiose , Compostos de Cálcio , Desnitrificação , Nitratos , Nitrogênio , Oxirredução
9.
Ecotoxicol Environ Saf ; 225: 112735, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478979

RESUMO

BACKGROUND: The kidney toxicity of fluoride exposure has been demonstrated in animal studies, and a few studies have reported kidney function injury in children with fluoride exposure. However, epidemiological information for the effects of long-term fluoride exposure on adult kidney function remains limited. METHODS: We conducted a cross-sectional investigation in Wenshui County, Shanxi Province to examine the association between fluoride exposure and kidney function in adults, and a total of 1070 adults were included in our study. Urinary fluoride concentrations were measured using the national standardized ion selective electrode method. And markers of kidney function injury (urinary NAG, serum RBP, serum Urea, serum C3, serum UA and serum αl-MG) were measured using automatic biochemical analyzer. Multivariate linear regression analysis and binary logistic regression model were used to assess the relationship between urinary fluoride and markers of kidney function injury. RESULTS: Urinary fluoride was positively correlated with urinary NAG and serum Urea, negatively correlated with serum C3. In multivariate linear regression models, every 1 mg/L increment of urinary fluoride was associated with 1.583 U/L increase in urinary NAG, 0.199 mmol/L increase in serum Urea, 0.037 g/L decrease in serum C3 after adjusting for potential confounding factors. In the binary logistic regression model, higher levels of urinary fluoride were associated with an increased risk of kidney function injury. Determination of kidney function based on urinary NAG, every 1 mg/L increment in the urinary fluoride concentrations was associated with significant increases of 22.8% in the risk of kidney function injury after adjusting for potential confounding factors. Sensitivity analysis for the association between urinary fluoride concentrations and markers of kidney function (urinary NAG, serum Urea, and serum C3) by adjusting for the covariates, it is consistent with the primary analysis. CONCLUSIONS: Our study suggests that long-term fluoride exposure is associated with kidney function in adults, and urinary NAG is a sensitive and robust marker of kidney dysfunction caused by fluoride exposure, which could be considered for the identification of early kidney injury in endemic fluorosis areas.


Assuntos
Fluoretos , Rim , Animais , China/epidemiologia , Estudos Transversais , Fluoretos/análise , Fluoretos/toxicidade , Rim/química , Análise Multivariada
10.
Microb Pathog ; 161(Pt A): 105210, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34563609

RESUMO

Colonization and development of the gut microbiome during early life is important in establishing a host-microbial symbiotic relationship. It contributes to maintaining health and well-being throughout the life span. To date, early longitudinal development of intestinal microflora in the ileum micro-ecology of the Yimeng black goats (YBGs) is rare. The purpose of this research was to study the effect of milk replacer with age on the ileal microbiota growth and maturation in YBGs throughout the post-weaning phase. The newborn YBGs (n = 24) were divided into two groups, i.e., milk replacer (R group) and control group (B group). The microbiome of Ileum was observed on days 15, 25, 45, and 75. When compared with baseline (B group), the R group's alpha diversity was lower (day 15, 25, 45), but it gradually approached and exceeded the baseline in the later stages (day 75). On the time axis, the richness of intestinal microflora was increased with age, but there was no statistically significant difference. The relative abundances of Proteobacteria, Firmicutes, Peptoclustridium, Lachnospiraceae, and Prevotellaceae showed a continuous trend of increase initially. They then decreased except Ruminococcaceae, which reflected the gradual maturity of intestinal microbial development. Milk replacer treatment temporarily increased the abundance of Actinomycetes (day 25 and 45), while the relative proportion of several intestinal bacteria such as Parasutterella, Megasphaera, Prevotellaceae, Akkermansia, and Subdoligranulum species were significantly higher in R group than in B group. The major changes in gut microflora composition might reflect positive effect of milk replacer on the development and maturation of the intestine during the early stage, connecting with substrate availability in the gut. Our study provides an effective strategy to promote the development of the gut microbiome, which is helpful for a smooth transition during the early-weaning period in YBGs.

11.
Int J Clin Exp Pathol ; 14(7): 845-854, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367416

RESUMO

A Disintegrin and metalloproteinase 17 (ADAM17) was proposed to cooperate with NF-κB p65, promoting tumorigenesis and progression of several human cancers. However, the role of ADAM17 remains unknown in human esophageal squamous cell carcinoma (ESCC). In this study, gene expression analyses and cell viability assays suggested that knockdown of ADAM17 suppressed ESCC cell viability. Gene expression analyses and ChIP-qPCR revealed that NF-κB p65 positively regulated ADAM17 expression by binding to the ADAM17 promoter. Rescue experiments showed that overexpression of ADAM17 in NF-κB p65-depleted ESCC cells restored cell viability. In addition, western blot analyses and ChIP-qPCR indicated that ADAM17 was responsible for the persistent activation of NF-κB p65 and contributed to ADAM17 expression in ESCC cells. In conclusion, we propose that ADAM17-activated NF-κB p65 signaling positively regulates ADAM17 expression, and facilitates ESCC cell viability.

13.
Front Genet ; 12: 686993, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276787

RESUMO

Germline mosaicism should be suspected when the same de novo mutations are identified in a second pregnancy with asymptomatic parents. Our study aims to find a feasible approach to reveal the existence of germline mosaicism. Multiplex Ligation-dependent Probe Amplification was performed on a Duchenne muscular dystrophy affected pedigree to detect deletion mutations. Then gap-polymerase chain reaction was performed to amplify the breakpoints junction sequence. Droplet digital polymerase chain reaction was utilized to identify the mutation frequencies in healthy parents. The same deletion in the exon 51 of the dystrophin gene, which was 50,035 bp in size, was detected in the proband and the fetus but not in their parents. Droplet digital polymerase chain reaction analysis of peripheral blood samples revealed mutant alleles of 3.53% in maternal blood cells. We here report a case of maternal low-level mosaicism confirmed by droplet digital polymerase chain reaction in peripheral blood samples, which reveals the existence of germline mosaicism. Gap-polymerase chain reaction combined with droplet digital polymerase chain reaction provide insights into the detection of germline mosaicism.

14.
Hum Mutat ; 42(11): 1429-1442, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34273908

RESUMO

Xq28 duplication syndrome (MIM# 300815) is a severe neurodevelopmental disorder in males due to MeCP2 overexpression. Most females with MECP2 duplication are asymptomatic carriers, but there are phenotypic heterogeneities. Skewed X-chromosome inactivation (XCI) can protect females from exhibiting clinical phenotypes. Herein we reported two asymptomatic females (mother and grandmother) with interstitial Xq28 duplication. AR and RP2 assays showed that both had extremely skewed XCI, the Xq28 duplicated chromosome was inactivated in the mother, but was surprisingly activated in the grandmother. Interestingly, by combining RNA sequencing and whole-exome sequencing, we confirmed that XIST only expressed in the Xq28 duplication chromosomes of the two females, indicating that the Xq28 duplication chromosomes were inactive. Meanwhile, MECP2 and most XCI genes in the duplicated X-chromosomes were not transcriptionally expressed or upregulated, precluding major clinical phenotypes in the two females, especially the grandmother. We showed that XCI status detected using RNA sequencing was more relevant for establishing the clinical phenotype of MECP2 duplication in females. It suggested that there were other factors maintaining the XCI status in addition to DNA methylation, a possible additional inhibition mechanism occurred at the transcriptional level in the unmethylated X-chromosome, counter balancing the MECP2 duplication's detrimental phenotype effects.

15.
Front Aging Neurosci ; 13: 682908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113247

RESUMO

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI). Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6-12 months after stroke. Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07-47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03-40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (P trend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82-0.99). Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.

16.
Chem Commun (Camb) ; 57(54): 6612-6615, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34116566

RESUMO

Negative ion mode paper spray mass spectrometry (PS-MS) suffers from intense background noise and unstable MS signal. For the first time, we reported fluorinated boron nitride nanosheet (h-FBN) assisted negative ion PS-MS for the detection of a series of molecules. We demonstrated that the introduction of h-FBN can greatly improve the detection sensitivity and signal stability in the negative ion mode.


Assuntos
Compostos de Boro/química , Halogenação , Limite de Detecção , Espectrometria de Massas/métodos , Papel , Nanoestruturas/química , Razão Sinal-Ruído
17.
Am J Transl Res ; 13(4): 2350-2364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017394

RESUMO

OBJECTIVE: Myocardial ischemia reperfusion (MI/RI) stresses the pathological process of progressive aggravation of tissue damage in ischemic myocardium. Isoflurane (ISO) is cardioprotective in MI/RI. Thus, this work aimed to identify the mechanism of isoflurane (ISO) post-treatment in MI/RI by regulating microRNA-378 (miR-378) and mitogen-activated protein kinase 1 (MAPK1). METHODS: A MI/RI model was established by ligating the left anterior descending coronary artery in mice. The modeled mice were injected with ISO or miR-378 or MAPK1 to define their roles in hemodynamics, myocardial injury, cell apoptosis and inflammatory infiltration of mice. CD45, miR-378 and MAPK1 levels were detected. Dual luciferase reporter gene assay was utilized for detection of the targeting connection of miR-378 and MAPK1. RESULTS: Reduced miR-378 and elevated MAPK1 existed in MI/RI. ISO elevated miR-378 to target MAPK1. ISO improved hemodynamics and myocardial injury, reduced apoptosis rate and inflammatory infiltration in MI/RI mice. Up-regulated miR-378 further enhanced the protective effect of ISO on MI/RI mice. Depleting MAPK1 reversed the effects of suppressed miR-378 on MI/RI. CONCLUSION: This study highlights that elevating miR-378 strengthens the isoflurane-mediated effects on MI/RI in mice via suppressing MAPK1, which provides a potential treatment for MI/RI.

18.
Nanoscale ; 13(20): 9364-9370, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33999091

RESUMO

The widespread coronavirus disease 2019 (COVID-19) has been declared a global health emergency. As one of the most important targets for antibody and drug developments, the Spike RBD-ACE2 interface has received extensive attention. Here, using molecular dynamics simulations, we explicitly analyzed the energetic features of the RBD-ACE2 complex of both SARS-CoV and SARS-CoV-2. Despite the high structural similarity, the binding strength of SARS-CoV-2 to the ACE2 receptor is estimated to be -16.35 kcal mol-1 stronger than that of SARS-CoV. Energy decomposition analyses identified three binding patches in SARS-CoV-2 RBD and eleven key residues (F486, Y505, N501, Y489, Q493, L455, etc.), which are believed to be the main targets for drug development. The dominating forces arise from van der Waals attractions and dehydration of these residues. Compared with SARS-CoV, we found seven mutational sites (K417, L455, A475, G476, E484, Q498 and V503) on SARS-CoV-2 that unexpectedly weakened the RBD-ACE2 binding. Interestingly, the E484 site is recognized to be the most repulsive residue at the RBD-ACE2 interface, indicating that from the energy point of view, a mutation of E484 would be beneficial to RBD-ACE2 binding. This is in line with recent findings that it is mutated by lysine (E484K mutation) in the rapidly spreading variants of COVID-19 belonging to the B.1.351 and P.1 lineages. In addition, this mutation is reported to cause virus neutralization escapes from highly neutralizing COVID-19 convalescent plasma. Thus, further efforts are required to probe its functional relevance. Overall, our results present a systematic understanding of the energetic binding features of SARS-CoV-2 RBD with the ACE2 receptor, which can provide a valuable insight for the design of SARS-CoV-2 drugs and identification of cross-active antibodies.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2 , Sítios de Ligação , COVID-19/terapia , Humanos , Imunização Passiva , Simulação de Dinâmica Molecular , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
19.
Front Oncol ; 11: 622085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796458

RESUMO

High iodine can alter the proliferative activity of thyroid cancer cells, but the underlying mechanism has not been fully elucidated. Here, the role of high iodine in the proliferation of thyroid cancer cells was studied. In this study, we demonstrated that high iodine induced the proliferation of BCPAP and 8305C cells via accelerating cell cycle progression. The transcriptome analysis showed that there were 295 differentially expressed genes (DEGs) in BCPAP and 8305C cells induced by high iodine, among which CDK1 expression associated with the proliferation of thyroid cancer cells induced by high iodine. Moreover, the western blot analysis revealed that cells exposed to high iodine enhanced the phosphorylation activation of AKT and the expression of phospho-Wee1 (Ser642), while decreasing the expression of phospho-CDK1 (Tyr15). Importantly, the inhibition of AKT phosphorylation revered the expression of CDK1 induced by high iodine and arrested the cell cycle in the G1 phase, decreasing the proliferation of thyroid cancer cells induced by high iodine. Taken together, these findings suggested that high iodine induced the proliferation of thyroid cancer cells through AKT-mediated Wee1/CDK1 axis, which provided new insights into the regulation of proliferation of thyroid cancer cells by iodine.

20.
Chem Biol Interact ; 341: 109451, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33798506

RESUMO

The pathogenesis of rheumatoid arthritis (RA) is characterized by synoviocyte hyperplasia and proinflammatory cytokine secretion, as well as the destruction of cartilage and bone. Glaucocalyxin A (GLA) is an alkaloid derived from a Chinese medicinal plant that exhibits anti-inflammatory, anti-tumor and neuroprotective properties. We investigated the effects of GLA on RA-fibroblast-like synoviocytes (FLS cells), and collagen-induced arthritis (CIA), and further explored the underlying mechanisms. GLA inhibited TNF-a-induced RA-FLS proliferation, increased apoptotic ratios and upregulated levels of caspase-3, cleaved PARP, and Bax. GLA also inhibited the expression of IL-10, IL-1ß, and IL-6 in vitro. Levels of p-STAT3 were downregulated in a dose-dependent manner. Over-expression of STAT3 partly neutralized the GLA-mediated elevation of caspase-3 and cleaved PARP levels as well as the downregulation of IL-10, IL-1B and IL-6 expression levels. This suggests that GLA inactivated the STAT3 pathway. Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model were inhibited effectively by GLA. Taken together, our data suggest that GLA is a potential long-term therapeutic agent for patients with RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Fator de Transcrição STAT3/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos Endogâmicos DBA , Ratos Wistar , Fator de Transcrição STAT3/genética , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Células Th17/efeitos dos fármacos , Células Th17/fisiologia , Fator de Necrose Tumoral alfa/farmacologia
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