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1.
Lett Appl Microbiol ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33550599

RESUMO

Candida albicans is one of the most common clinical pathogenic microorganisms and it is becoming a serious health threat, particularly to immunocompromised populations. Drug resistance of Candida species has also frequently emerged, and combination therapy for fungal infections has attracted considerable attention. In this study, we established the Qinling Mountains myxobacterial secondary metabolites library and a synergic assay in combination with ketoconazole against C. albicans was introduced for metabolites screening. Two active compounds with synergic anticandidal activities were obtained, which were identified as trans-resveratrol and cis-resveratrol. According to our study, resveratrol can reduce the dosage to 1/64 of ketoconazole as well as itraconazole. Furthermore, synergistic anticandidal activity of resveratrol combined with azoles was verified against a panel of clinical C. albicans isolates, and the combination strategy enhanced the azoles susceptibility of three fluconazole-resistant isolates. These findings suggest that resveratrol enhances the efficacy of azoles and provides a promising application in therapy of C. albicans infection.

3.
Artigo em Chinês | MEDLINE | ID: mdl-33535333

RESUMO

Objective: To identify the differential expression of Peroxiredoxin 4 (PRDX4) in alveolar macrophages (AMs) from patients with silicosis in different phases using Western blot. Methods: From June 2017 to June 2018, Twelve pneumoconiosis patients in the pneumoconiosis Department of Beidaihe Sanitarium were selected by random sampling. A msong them, there were 4 groups, that was lung with dust, silicosis with grade one, silicosis with grade two, silicosis with grade three. There were 3 persons in each group, a total of 12. AMs was obtained by filtration and centrifugation. The intracellular protein was extracted and PRDX4 was detected by using Western blot method. Results: It results showed that PRDX4 was expressed in AMs in 4 groups; with the increase of fibrosis, the average relative expression of PRDX4 in AMs was 0.258±0.026, 0.214±0.012, 0.180±0.004, 0.165±0.008. The highest expression level was in the lung with dust group, and the lowest was in the silicosis with grade three group. The difference of the expression level of PRDX4 protein in AMs between groups was statistically significant (P<0.05) . Conclusion: This experiment verified that PRDX4 expressed differentially in AMs in patients with silicosis. With the development of silicosis, PRDX4 expression in AMs reduced significantly.


Assuntos
Pneumoconiose , Silicose , Humanos , Pulmão , Macrófagos Alveolares , Peroxirredoxinas
4.
Artigo em Chinês | MEDLINE | ID: mdl-33535334

RESUMO

Objective: To explore the relationship between input and output of occupational health funds, and to provide basis for relevant departments to make decisions. Methods: In September 2018, a state-owned iron ore in Hebei Province (mining history of more than 10 years, which can represent the general type of iron ore) was selected as the research object. Through the investigation and collection of enterprise general situation, occupational health input, loss and output related indicators, the iron mine occupational health expenditure input-output table and model were established, and the digital relationship between the investment and output was solved by MATLAB software. Results: The labor consumption in the departments of underground mining, open pit mining, crushing and rock discharging, transportation, tailings and mineral processing (taking labor wages as reference) were 756.46, 1.281.78, 987.61, 1 570.71, 50.956 and 18.9116 million yuan/year respectively. The output value of each sector is 11 207.19, 18 989.95, 15 176.40, 25 294.00, 7.704.94 and 280.1797 million yuan/year respectively. The ratio of health input to total output was 0.004 5, and the ratio of occupational health input to output was 1/0.046. Conclusion: The input-output table model of occupational health in iron mine can reflect the relationship between input and output of occupational health funds. The input situation of the coal mine is poor, and the input does not bring obvious occupational health benefits.


Assuntos
Saúde do Trabalhador , Ferro , Mineração
5.
Artigo em Chinês | MEDLINE | ID: mdl-33535351

RESUMO

The human epigenetic gene of SET domain containing 2 (SETD2) is located at the cytogenetic band p21.31 of chromosome 3, which encodes the histone3 lysine36 trimethyltransferase SETD2, the major enzyme that catalyzes the trimethylation of lysine 36 on histone 3 (H3K36me3) of human. SETD2 involves in many pathologic and physiological processes such as transcriptional elongation, DNA damage repair, alternative splicing, epigenetic modifications of gene expression, viral immunology, embryonic development, and angiogenesis. A growing list of tumor types including renal cell carcinoma and mesothelioma develops with mutation or inactivation of SETD2. SETD2 loss-of-function promotes the occurrences and development of cancers by inhibiting process of transcription extension, damage repair, cell cycles, apoptosis and cell metabolism. The under expression and mutation of SETD2 is synthetically lethal with the inhibition of G2M checkpoint and PI3K-AKT pathway and SETD2 is considered as a potential epigenetic therapy targets. Furthermore, a loss of SETD2 indicates worse pathological features. There are huge prospects in the diagnosis and treatment of related cancers.


Assuntos
Neoplasias , Fosfatidilinositol 3-Quinases , Epigênese Genética , Histonas/metabolismo , Humanos , Mutação , Neoplasias/genética
6.
Eur Rev Med Pharmacol Sci ; 25(2): 812-819, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33577036

RESUMO

OBJECTIVE: The aim of this study was to explore the role of pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, in cardiac fibrosis of diabetic mice. MATERIALS AND METHODS: A total of 60 adult male C57/B6 mice were divided into 3 groups using a random number table, namely, control group (Sham group, n=20), diabetic cardiomyopathy group (DCM group, n=20), DCM + PIO group (n=20). Streptozocin (STZ) was injected into mice at a dose of 125 mg/Kg to induce the model of diabetes in vivo. After successful induction, mice in DCM + PIO group were intragastrically given PIO at 10 mg/kg/d once a day for 6 weeks. Meanwhile, those in Sham group and DCM group were given the same volume of normal saline. After 6 weeks, ejection fraction % (EF%), fraction shortening % (FS%) and heart rate of mice in each group were examined via echocardiography. Picrosirius red (PSR) staining assay was conducted to detect collagen deposition in myocardial tissues of mice in each group. The protein expression level of PPARγ in mouse myocardial tissues in each group was measured through Western blotting and immunohistochemical staining assays. Hematoxylin-eosin (H&E) staining assay was carried out to evaluate the myocardial hypertrophy of mice in each group. The protein expression level of transforming growth factor-ß (TGF-ß) in mouse myocardial tissues in each group was measured through immunohistochemical staining assay. In addition, Western blotting was employed to detect the expression of proteins related to the phosphate and tension homology deleted on chromsome ten (PTEN)/protein kinase B (AKT)/focal adhesion kinase (FAK) signaling pathway in myocardial tissues of mice in each group. RESULTS: The messenger ribonucleic acid (mRNA) and protein expression levels of PPARγ in mouse myocardial tissues were significantly lower in DCM group than those in Sham group (p<0.05). PPARγ agonist PIO could significantly increase the protein expression of PPARγ in myocardial tissues of DCM mice. The results of cardiac Doppler ultrasound revealed that PIO significantly upregulated EF% and FS% in DCM mice (p<0.05). Besides, PIO remarkably reduced collagen deposition and TGF-ß protein expression in myocardial tissues in DCM mice (p<0.05). H&E staining results showed that PIO notably attenuated myocardial hypertrophy in DCM mice (p<0.05). Furthermore, it was discovered that PIO markedly elevated PTEN protein in myocardial tissues of DCM mice and inhibited the phosphorylation of AKT and FAK proteins (p<0.05). CONCLUSIONS: The protective effect of PIO against cardiac fibrosis in diabetic mice may be related to its regulation on the PTEN/AKT/FAK signaling pathway. Our findings suggest that PIO is expected to become a targeted drug for the treatment of DCM in clinical practice.

7.
Eur Rev Med Pharmacol Sci ; 25(2): 957-967, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33577051

RESUMO

OBJECTIVE: To investigate the changes of CaM-CaMK-CREB signaling pathway and related neuron factors in hippocampus of rats after sevoflurane and propofol administration. MATERIALS AND METHODS: A total of 90 SD rats, half male and half female, were selected. They were randomized into anesthesia group (AG) and control group (CG), in which 30 rats under propofol anesthesia in the AG were included in group A, 30 rats under sevoflurane anesthesia were included in group B, and 30 rats under mixed ventilation of air and oxygen were included in the CG. Before (10 rats were killed in each group) and at the end of anesthesia (2 weeks of anesthesia and 7 days of Morris water maze test), rats were respectively killed and then an appropriate amount of hippocampus was separated. Human tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), calmodulin (CaM), calmodulin-dependent kinase Ⅱ a (CaMK II a), NMDA receptor 2B (NR2B), cysteine aspartate specific protease-3 mRNA (Caspase-3mRNA) and protein contents were detected. RESULTS: The latency of rats in group A and group B, as well as their times of crossing the original platform on 1, 4, and 7d were markedly higher than those of the CG, and those in group B were markedly lower than those in group A (p<0.001). The total distance of rats in group A and group B on 1, 4, and 7d was significantly higher than that of the CG, and that in group B was dramatically lower than that in group A (p<0.001). The speed of rats in the three groups ranged from 1d to 7d, and there was no significant difference at different time points (p>0.05). At the end of anesthesia, the expression levels of CaM mRNA and protein in hippocampus of rats in group A and group B were remarkably higher than those of the CG, and those of CaMK II a mRNA and protein were remarkably lower than those of the CG; the CaM mRNA and protein expression levels in hippocampus of group A were significantly higher than those of group B, and those of CaMK IL a mRNA and protein were significantly lower than those of group B (p<0.001). Simultaneously, the expression levels of NR2BmRNA, Caspase-3mRNA and protein in hippocampus of group A and group B were substantially higher than those of the CG, and those in group B were substantially lower than those in group A (p<0.001). What's more, the TNF-a and VEGF expression levels in hippocampus of group A and B were markedly higher than those of the CG, and those in group B were dramatically lower than those of group A (p<0.001). CONCLUSIONS: Sevoflurane anesthesia on the CaM-CaMK-CREB signaling pathway and learning and memory function of rats is less volatile, which does better in safeguarding stability.

8.
Biophys J ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33607086

RESUMO

The current COVID-19 pandemic has led to a devastating impact across the world. SARS-CoV-2 (the virus causing COVID-19) is known to use the receptor-binding domain (RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2 (ACE2) receptor expressed on many human cell types. The RBD-ACE2 interaction is a crucial step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2 interaction with the SARS-CoV-2 S protein has a higher affinity than its binding with the structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS outbreak. However, the biophysical mechanism behind such binding affinity difference is unclear. This study utilizes combined single-molecule force spectroscopy and steered molecular dynamics (SMD) simulation approaches to quantify the specific interactions between CoV-2 or CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between CoV-2 RBD and ACE2 range from 70 to 105 pN and are 30-40% higher than those of CoV-1 RBD and ACE2 under similar loading rates. SMD results indicate that CoV-2 RBD interacts with the N-linked glycan on Asn90 of ACE2. This interaction is mostly absent in the CoV-1 RBD-ACE2 complex. During the SMD simulations, the extra RBD-N-glycan interaction contributes to a greater force and prolonged interaction lifetime. The observation is confirmed by our experimental force spectroscopy study. After removing N-linked glycans on ACE2, its mechanical binding strength with CoV-2 RBD decreases to a similar level of the CoV-1 RBD-ACE2 interaction. Together, the study uncovers the mechanism behind the difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies to block SARS-CoV-2 entry.

10.
Clin Exp Dermatol ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33548083

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2 ) immune responses are dominant. SHANK-associated RH domain interacting protein (SHARPIN) is expressed at low levels in AD, resulting in the upregulation of signal transducer and activator of transcription3 (STAT3) and the Th2 cytokine, interleukin (IL)-33. However, the roles of SHARPIN in AD have not been fully elucidated. OBJECTIVES: Here, we aimed to evaluate the signaling interactions of SHARPIN and IL-33 to improve our understanding of the pathogenesis of AD. METHODS: Western blotting was used to detect the Janus kinase (JAK)/STAT signaling proteins and IL-33 protein in HaCaT cells to determine the key proteins mediating the interaction between SHARPIN and IL-33. The findings were validated by immunofluorescence and immunohistochemical staining. Chromatin immunoprecipitation assays were employed to evaluate the activity of STAT3 at the IL-33 promoter. RESULTS: We found that phospho-JAK2 and phospho-STAT3 were upregulated in SHARPIN-knockdown HaCaT cells. Subsequent chromatin immunoprecipitation assays revealed that STAT3 bound to the IL-33 promoter to mediate IL-33 expression. Moreover, SHARPIN-mediated expression of IL-33 was reduced after treatment of HaCaT cells with the JAK/STAT inhibitor ruxolitinib. STAT3 and IL-33 expression levels were higher in AD skin lesion tissues than in normal skin tissues. CONCLUSIONS: These findings suggested that SHARPIN modulated inflammation in HaCaT cells by inhibiting JAK/STAT signaling, supporting the application of SHARPIN as a potential therapeutic target for AD.

11.
Poult Sci ; 100(2): 1004-1007, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518058

RESUMO

Our study was aimed to investigate the effects of dietary metabolizable energy (ME) and crude protein (CP) levels on the digestive physiology in the jejunal fluid of Muscovy ducks to provide digestive parameters for in vitro digestion. There were 6 ME levels (11.0, 11.5, 12.0, 12.5, 13.0, and 13.5 MJ/kg; Exp. 1) and six CP levels (140, 155, 170, 185, 200, and 215 g/kg; Exp. 2) and each treatment included 6 replicates with 3 ducks each replicate. In Exp. 3, the comparison of energy utilization was investigated between in vivo and in vitro using the digestion parameters obtained from Exp. 1 and 2. As dietary ME was increased, the chymotrypsin activity was increased linearly (P < 0.05), and the concentrations of Ca2+, K+, and Mg2+ were increased quadratically (P < 0.05) in the jejunal fluid. As dietary CP was increased, amylase activity was increased linearly (P < 0.05), whereas trypsin and chymotrypsin activities and Ca2+ concentration were increased quadratically (P < 0.05). The pH values were decreased quadratically with the increased dietary ME or CP levels (P < 0.05). The optimal digestion parameters for energy feedstuffs with 307.26 U/mL amylase, 54.68 U/mL trypsin, 24.90 U/mL chymotrypsin, 104.39 mmol/L Na+, 51.25 mmol/L Cl-, and pH 7.79; for protein feedstuffs with 381.88 U/mL amylase, 72.84 U/mL trypsin, 11.98 U/mL chymotrypsin, 93.53 mmol/L Na+, 46.25 mmol/L Cl-, and pH 7.80, respectively. Using the optimal digestion parameters for in vitro digestion, energy utilization in vitro reflected the degree of the apparent energy utilization of corn, sorghum, and barley as well as true energy utilization of soybean meal, rapeseed meal, and cottonseed meal in vivo and the variation of digestion was lower in vitro than in vivo.

12.
Sci Adv ; 7(5)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33571117

RESUMO

This paper reports a flexible electronics-based epidermal biomicrofluidics technique for clinical continuous blood glucose monitoring, overcoming the drawback of the present wearables, unreliable measurements. A thermal activation method is proposed to improve the efficiency of transdermal interstitial fluid (ISF) extraction, enabling extraction with a low current density to notably reduce skin irritation. An Na+ sensor and a correction model are proposed to eliminate the effect of individual differences, which leads to fluctuations in the amount of ISF extraction. An electrochemical sensor with a 3D nanostructured working electrode surface is designed to enable precise in situ glucose measurement. A differential structure is proposed to eliminate the effect of passive perspiration, which leads to inaccurate blood glucose prediction. Fabrications of the epidermal biomicrofluidic device including formation of flexible electrodes, nanomaterial modification, and enzyme immobilization are fully realized by inkjet printing to enable facile manufacturing with low cost, which benefits practical production.

13.
Animal ; : 100027, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573989

RESUMO

Lactose and somatic cell score (SCS) are major economic traits of milk. However, for many countries, they are typically not directly considered in the national genetic evaluation of Simmental cattle. This study aimed to estimate the genetic relationships between lactose, SCS, and growth traits of Simmental cattle to provide information for the national genetic evaluation of the selection of traits of this cattle population. The data of 1781 animals with 6519 records obtained over a period of 41 years (1975-2016) were collected from Xinjiang Hutubi Farm, China. The analyzed traits included 305 days of milk yield (305MY), milk fat percentage (MFP), milk protein percentage (MPP), milk lactose percentage (MLP), total solids (TS), SCS, body height (BH), body length (BL), chest girth (CG), abdominal circumference (AC), rump width (RW), rump length (RL), leg circumference (LC), and cannon circumference (CC). The multiple-trait repeatability model was adopted to estimate (co)variance components using the average information-restricted maximum likelihood method implemented using the DMU statistical package. The heritability estimates for milk components and growth traits ranged from 0.09 (SCS) to 0.51 (BH). Genetic correlations for milk components ranged from 0.03 ±â€¯0.14 (MFP and MLP) to 0.81 ±â€¯0.08 (MFP and MPP). Genetic correlation between MLP and SCS was moderate and negative (-0.50 ±â€¯0.15) compared with that among other traits. Genetic correlations between the milk components and growth traits ranged from 0.00 ±â€¯0.07 (305MY and RW) to -0.64 ±â€¯0.15 (MLP and BL). Genetic correlations of BL, LC, RW, and RL with MLP were moderate to high and negative ranging from -0.39 to -0.64. Somatic cell score showed the highest correlation with BL (0.41) followed by LC (0.21). An increase in MLP would result in an increase in 305MY or TS and a decrease in BL, LC, RW, and RL. Additionally, a decrease in SCS would occur with the selection of increased MLP and reduced BL. We conclude that selection based on easily and inexpensively measured growth traits could improve the milk quality from Simmental cattle.

14.
J Nutr Health Aging ; 25(3): 335-339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575725

RESUMO

BACKGROUND AND PURPOSE: As a very common risk of adverse outcomes of the ischemic stroke patients, sarcopenia is associated with infectious complications and higher mortality. The goal of this retrospective study is to explore the predictive value of serum Cr/CysC ratio in acute ischemic stroke patients receiving nutritional intervention. METHODS: We reviewed adult patients with AIS from December 2019 to February 2020. Patients with acute kidney injury were excluded and all patients received nutritional intervention during a 3-month follow-up period. We collected baseline data at admission including creatinine and cystatin C. The primary poor outcome was major disability (modified Rankin Scale score ≥ 4) at 3 months after AIS. RESULTS: A total of 217 patients with AIS were identified for this study. Serum Cr/CysC ratio was significantly correlated with NIHSS at discharge, 1-month modified Rankin Scale score, and 3-month modified Rankin Scale score. During 3 months, 34 (15.70%) patients had a poor outcome after AIS and 11 (5.10%) patients died within 30 days. In multivariable logistic regression analyses, serum Cr/CysC ratio at admission was independently associated with 3-month poor outcomes (OR: 0.953, 95% CI: 0.921-0.986, p = .006) and 30-day mortality (OR: 0.953, 95% CI: 0.921-0.986, p = .006). CONCLUSION: As a blood biochemical indexes reflecting the muscle mass and aiding in risk stratification, Cr/CysC ratio at admission could be used as a predictor of 30-day mortality and long-term poor prognosis in AIS patients.

15.
Eur Rev Med Pharmacol Sci ; 25(2): 1097-1100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33577066

RESUMO

OBJECTIVE: The aim of the present study was to assess the value of inflammatory factors procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP) in the early diagnosis and evaluation of novel coronavirus pneumonia (COVID-19). MATERIALS AND METHODS: The data of 140 patients with pneumonia in our hospital, including 70 who had COVID-19 and 70 who had community-acquired pneumonia (CAP), were statistically analyzed. The levels of PCT, IL-6, and CRP were measured and statistically analyzed to determine the differences between the two groups. The differences in the COVID-19 group were analyzed after subgrouping into the ordinary type, severe type, and critical type. RESULTS: The PCT and CRP levels in the COVID-19 group were statistically lower than those in the CAP group (p < 0.05), but IL-6 was not statistically different between the two groups (p > 0.05). Statistically significant differences existed in IL-6 and CRP when comparing the COVID-19 subgroups of the critical type, severe type, and ordinary type (p < 0.05). However, there was no clinical meaning in the evaluation of the difference in PCT levels among the three subgroups with COVID-19. CONCLUSIONS: PCT and CRP could be used as indicators in the differentiation between COVID-19 and CAP, but IL-6 was of little significance in the differentiation. The higher the IL-6 and CRP, the more severe the condition of COVID-19 might be.

16.
Animal ; : 100172, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33589350

RESUMO

Some grain processing by-products rich in digestible fiber are good feed resources for ruminants. This experiment was conducted to investigate the effects of replacing a portion of corn and corn stover with the combinations of corn bran and soybean hulls in the diet of fattening lambs on nutrient digestion, rumen microbial protein synthesis, and growth performance. A total of 36 Dorper × Small Thin-Tailed crossbred ram lambs (BW = 22.2 ±â€¯0.92 kg; mean ±â€¯SD) were randomly divided into three groups, and each group was fed 1 of 3 treatment diets: 1) 0% corn bran and soybean hulls (control); 2) 9% corn bran and 9% soybean hulls (18MIX); and 3) 17% corn bran and 17% soybean hulls (34MIX). The feeding experiment was conducted for 70 days, with the first 10 days for adaption. The DM intake was higher for 34MIX (1635.3 g/d) than for control diet (1434.7 g/d; P = 0.001). Lambs fed 18MIX and 34MIX diets (230.2 and 263.6 g/d, respectively) had higher average daily gain and feed efficiency than those fed control diet (194.8 g/d; P < 0.01). Dry matter and NDF digestibility for 34MIX group (60.9 and 49.5%) were higher than for control (55.2 and 41.3%; P < 0.01). No difference was observed in nitrogen digestibility among treatment diets (P = 0.778). The lambs fed 34MIX diet excreted more urinary purine derivatives, indicating that more microbial protein was yielded than those fed control diet (P < 0.01), while 18MIX was not different from the other two diets (P > 0.05). The metabolizable protein supplies were improved with increasing co-products inclusion rate. The results indicated that corn bran and soybean hulls in combination can effectively replace a portion of corn and corn stover in the ration of finishing lambs with positive effect on nutrient digestion and growth performance.

18.
J Prev Alzheimers Dis ; 8(2): 224-233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33569571

RESUMO

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. OBJECTIVES: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression. METHODS: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients' peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm. RESULTS: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer's Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different. CONCLUSIONS: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients' peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application.

19.
Zhonghua Gan Zang Bing Za Zhi ; 29(1): 67-71, 2021 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-33541026

RESUMO

Objective: To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen (APAP) in mice. Methods: Colgalt2(+/+) wild-type control mice and Colgalt2(-/-) mice (all C57BL/6J strains) were selected as the research subject. APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury. The mouse were divided into four groups: Colgalt2(+/+) wild-type control group, Colgalt2(+/+) wild-type drug group (APAP 500 mg/kg), Colgalt2(-/-) control group, and Colgalt2(-/-) drug group (APAP 500 mg/kg). The survival rate was measured to plot survival curve. Liver function was evaluated by detecting serum ALT and AST levels. Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury. Western blot was used to detect protein c-Jun N-terminal kinase (JNK)-related liver injury. Results: Compared with Colgalt2(+/+) mice, the survival rate was significantly increased after giving APAP to Colgalt2(-/-) mice (86.7% vs. 40%), and liver cell necrosis and inflammatory cell infiltrates of Colgalt2(+/+) mice were milder. Serum ALT, and AST level was significantly decreased [ALT: (5 291.9 ± 1 016.34) U/L vs. (1 616.9 ± 330.65) U/L, P = 0.000; AST: (4 978.0 ± 1 028.43) U/L vs. (1 851.0 ± 437.55) U/L, P = 0.000]. The expression level of JNK was significantly decreased in liver tissue. Conclusion: Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen (APAP) in mice. Therefore, Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Deleção de Genes , Glicosiltransferases/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
20.
Zhonghua Nei Ke Za Zhi ; 60(2): 122-127, 2021 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-33503722

RESUMO

Objective: To investigate the intrinsic organization of cortical circuitry in individuals with subjective cognitive decline (SCD) via resting-state functional magnetic resonance imaging (rs-fMRI) connectome analysis and its correlation with cognitive level. Methods: From June 2017 to November 2019, thirty-six middle-aged and elderly individuals with complaints of memory decline and 32 normal controls (NC) were enrolled from communities in Nanjing. We collected cognitive scale performance,T1-weighted imaging (T1WI) and rs-fMRI data of all subjects. There were 5 males and 31 females in the SCD group, with an average age of (64±5) years. In the NC group, there were 8 males and 24 females, with an average age of (65±5) years. Preprocessing of rs-fMRI data was conducted, then the cerebral cortex was divided into 333 cortical parcels (nodes) and 10 predefined communities according to the prior template. Further, we established full connection matrices between cortical parcels and calculated the within-module degree (WMD) and participation coefficient (PC) of each node based on the matrices. The WMD and PC values were compared between the SCD and NC groups,and their correlations with cognitive scale performance were analyzed. Results: Compared to the NC group,the SCD group showed increased WMD in the dorsolateral prefrontal cortex (DLPFC)(P<0.05,FDR corrected) and the middle frontal gyrus (P<0.005,uncorrected) of the right frontoparietal network (FPN). The SCD group also showed decreased WMD(P<0.05,FDR corrected) in the superior occipital gyrus of the left visual network (VN) and decreased PC (P<0.005,uncorrected) in the supramarginal gyrus of the left dorsal attention network (DAN). The WMD values in the DLPFC showed significant positive correlations with the auditory verbal learning test (AVLT)short-delayed memory (r=0.364,P=0.029),recognition memory (r=0.364, P=0.029) and the Boston naming test scores (BNT, r=0.356, P=0.033)in the SCD group. The PC values in the supramarginal gyrus were significantly positively correlated with the BNT scores (r=0.413, P=0.012) in the SCD group. Conclusion: Cortical network imbalance and reconstruction characterized by decreased intra-module connectivity of VN and inter-module connectivity of DAN exist in SCD subjects,while increased intra-module connectivity of FPN may serve in a compensatory way for the early cognitive decline.


Assuntos
Disfunção Cognitiva , Conectoma , Idoso , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Lobo Frontal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
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