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1.
Stroke ; 55(10): 2431-2438, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39315825

ABSTRACT

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.


Subject(s)
Ischemic Stroke , Magnetic Resonance Imaging , Humans , Male , Middle Aged , Female , Aged , Prospective Studies , Prognosis , Ischemic Stroke/diagnostic imaging , Adult , Aged, 80 and over , Stroke/diagnostic imaging , Stroke/etiology , Stroke/epidemiology
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 581-591, 2024 Aug.
Article in Zh | MEDLINE | ID: mdl-39223023

ABSTRACT

Vigilance is a sensitive ability to respond to small changes in the environment and it is a major component of various cognitive performance tasks.Professionals in a variety of fields require high physical and vigilance performance during the working process to ensure productivity,workplace safety,and their own safety. This article reviews the research progress in vigilance in terms of the examination methods,influencing factors,and drug treatment in recent years,aiming to improve the understanding of vigilance and provide support for the research on vigilance and clinical treatment of vigilance-related dysfunctions.


Subject(s)
Attention , Humans
3.
Proc Natl Acad Sci U S A ; 116(20): 10156-10161, 2019 05 14.
Article in English | MEDLINE | ID: mdl-31028142

ABSTRACT

Transient receptor potential canonical type 6 (TRPC6) is a nonselective receptor-operated cation channel that regulates reactive fibrosis and growth signaling. Increased TRPC6 activity from enhanced gene expression or gain-of-function mutations contribute to cardiac and/or renal disease. Despite evidence supporting a pathophysiological role, no orally bioavailable selective TRPC6 inhibitor has yet been developed and tested in vivo in disease models. Here, we report an orally bioavailable TRPC6 antagonist (BI 749327; IC50 13 nM against mouse TRPC6, t1/2 8.5-13.5 hours) with 85- and 42-fold selectivity over the most closely related channels, TRPC3 and TRPC7. TRPC6 calcium conductance results in the stimulation of nuclear factor of activated T cells (NFAT) that triggers pathological cardiac and renal fibrosis and disease. BI 749327 suppresses NFAT activation in HEK293T cells expressing wild-type or gain-of-function TRPC6 mutants (P112Q, M132T, R175Q, R895C, and R895L) and blocks associated signaling and expression of prohypertrophic genes in isolated myocytes. In vivo, BI 749327 (30 mg/kg/day, yielding unbound trough plasma concentration ∼180 nM) improves left heart function, reduces volume/mass ratio, and blunts expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload. Additionally, BI 749327 dose dependently reduces renal fibrosis and associated gene expression in mice with unilateral ureteral obstruction. These results provide in vivo evidence of therapeutic efficacy for a selective pharmacological TRPC6 inhibitor with oral bioavailability and suitable pharmacokinetics to ameliorate cardiac and renal stress-induced disease with fibrosis.


Subject(s)
Cardiomegaly/drug therapy , Nephrosclerosis/drug therapy , TRPC6 Cation Channel/antagonists & inhibitors , Animals , Drug Evaluation, Preclinical , Fibrosis , HEK293 Cells , Heart/drug effects , Humans , Kidney/drug effects , Mice
4.
Bioorg Chem ; 94: 103392, 2020 01.
Article in English | MEDLINE | ID: mdl-31669093

ABSTRACT

The key functions of microtubules and the mitotic spindle in cell division make them attractive targets for cancer therapy. In this study, a series of 1-(benzofuran-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole derivatives was synthesized, and their antiproliferative activities against HCT116, HeLa, HepG2, and A549 cells were evaluated. 6-Methoxy-N-phenyl-3-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-1-yl)benzofuran-2-carboxamide (17g) exhibited the strongest antiproliferative activities, with IC50 values ranging from 0.57 to 5.7 µM. Mechanistic studies showed that 17g inhibited tubulin polymerization, leading to the disruption of mitotic spindle formation, cell cycle arrest in the G2/M phase, and apoptosis of A549 cells. A docking study indicated that 17g was a good molecular fit at the colchicine binding site of tubulin. These results showed that 17g is a potential anticancer compound that is worthy of further development as a tubulin polymerization inhibitor.


Subject(s)
Antineoplastic Agents/pharmacology , Benzofurans/pharmacology , Triazoles/pharmacology , Tubulin/metabolism , A549 Cells , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Benzofurans/chemical synthesis , Benzofurans/chemistry , Cell Cycle Checkpoints/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Membrane Potential, Mitochondrial/drug effects , Molecular Docking Simulation , Molecular Structure , Polymerization/drug effects , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry
5.
J Cell Biochem ; 120(2): 1122-1132, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30256444

ABSTRACT

The adipokine Chemerin has been reported to regulate differentiation and metabolism of adipocytes, but the mechanism underlying lipolysis is still largely unknown. The purpose of this study was to explore whether ERK1/2 pathway is involved in regulating Chemerin during bovine intramuscular mature adipocyte lipolysis. Intramuscular mature adipocytes of dairy bull calves were cultured in vitro and were treated with Chemerin or U0126, which is an inhibitor of ERK1/2 pathway. The results showed that TG content in cells was significantly decreased, glycerol and free fatty acid were significantly increased in cell culture media, and the expression of phosphorylated ERK1/2 in cells was increased in Chemerin-treated group, suggested that ERK1/2 pathway was involved in regulation of lipolysis by Chemerin. In addition, the expression of lipolytic-related critical factors ATGL, HSL, LPL, PPARα, UCP3, and CPT1 were upregulated, but the expression of adipogenic key factors, including PPARγ and C/EBPα were downregulated by Chemerin. Interestingly, all the effects of Chemerin on genes expression in intramuscular mature adipocytes or fat tissue were inhibited by U0126, showed that the function of Chemerin to promote adipose decomposition will be significantly weakened if the ERK1/2 pathway is suppressed, and confirmed that ERK1/2 pathway is involved in mediate Chemerin-enhanced lipolysis. In conclusion, the study demonstrated that Chemerin induce intramuscular mature adipocytes lipolysis through activation of the ERK1/2 pathway. Our research at least provide partial mechanisms of Chemerin on lipolysis and deposition of intramuscular fat tissue of dairy bull calves.

6.
Phys Chem Chem Phys ; 20(46): 29539-29548, 2018 Nov 28.
Article in English | MEDLINE | ID: mdl-30457617

ABSTRACT

We performed potential dependent second harmonic generation (SHG) measurements on the Si(111) electrolyte interface at different azimuthal angles and for different polarization combinations. When the external potential was biased from the equilibrium potential to the flatband potential (Efb), the SHG intensity decreased linearly with the potential when the azimuthal angle was oriented at 30°. This linearity extends well beyond the linear region of the Mott-Schottky plot as measured traditionally by capacitance measurements. When the external potential was scanned from Efb toward more negative potentials, the response of SHG intensity showed quadratic behavior and can be described by the parabolic model. The non-parabolic potential dependence cannot be explained with the parabolic model proposed from previous literature. Such asymmetric behavior only implied that the interfacial structure of the Si(111) electrode changes from semiconductor to metal with the applied electric potential biased negatively, i.e. with accumulation of electrons in the surface region. The anisotropic contribution from the Si(111) electrode can also significantly affect the SHG response as seen where the minimum of the potential dependent SHG curve shifts away from Efb.

7.
J Res Med Sci ; 22: 106, 2017.
Article in English | MEDLINE | ID: mdl-29026422

ABSTRACT

BACKGROUND: This study aims to evaluate the utility of the "Cross-Internal Ring" inguinal oblique incision for the surgical treatment of incarcerated indirect hernia (IIH) complicated with severe abdominal distension. MATERIALS AND METHODS: Patients of IIH complicated with severe abdominal distension were reviewed retrospectively. All patients received operation through the "Cross-Internal Ring" inguinal oblique incision. RESULTS: There were totally 13 patients were included, male to female ratio was 9-4. The time for patients to resume oral feeding varying from 2 to 5 days after operation, no complications include delayed intestinal perforation, intra-abdominal abscess, and incision infection happened. Average postoperative hospital stay was 5.2 days. All cases were followed up for 6-18 months. No recurrence or iatrogenic cryptorchidism happened. CONCLUSION: "Cross-Internal Ring" inguinal oblique incision is a simple, safe, and reliable surgical method to treat pediatric IIH complicated with severe abdominal distension.

8.
Neurochem Res ; 41(9): 2470-80, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27255602

ABSTRACT

To explore the effect of glycogen synthase kinase 3ß (GSK-3ß) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3ß was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3ß was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3ß silencing system was successfully developed and silencing GSK-3ß at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3ß silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3ß silence. Silencing GSK-3ß may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.


Subject(s)
Alzheimer Disease/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Memory/drug effects , RNA Interference , tau Proteins/metabolism , Animals , Disease Models, Animal , Glycogen Synthase Kinase 3 beta/genetics , Hippocampus/metabolism , Humans , Memory/physiology , Mice, Inbred C57BL , Neurons/metabolism , Phosphorylation/drug effects , tau Proteins/genetics
9.
Neurol Sci ; 37(1): 73-79, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26269422

ABSTRACT

This study was aimed to explore the molecular mechanism of Parkinson's disease (PD) development and discover underlying pathways and genes associated with PD. The microarray data of GSE22491 containing 10 samples from PD patients and 8 samples from healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses followed by Gene Ontology (GO) and pathway enrichment analyses and protein-protein interaction (PPI) network construction. Total 176 up-regulated DEGs and 49 down-regulated DEGs were identified. Totally, 39 GO terms and 72 pathways were closely related to PD. Pathway of neuronal system was enriched by 10 DEGs such as synapsin I (SYN1), glutamate receptor, ionotropic, N-methyl-D-aspartate 1 (GRIN1) and GRIN2D. In the PPI networks, 18 hub genes were obtained, such as GRIN2D and discs, large (Drosophila) homolog-associated protein 3 (DLGAP3). The pathway of neuronal system and its enriched DEGs may play important roles in PD progression. The DEGs such as SYN1, GRIN1, GRIN2D and DLGAP3 may become promising candidate genes for PD.


Subject(s)
Parkinson Disease/genetics , Parkinson Disease/metabolism , Cluster Analysis , Gene Expression Profiling/methods , Humans , Microarray Analysis , Principal Component Analysis , Signal Transduction/genetics , Signal Transduction/physiology
10.
Am J Emerg Med ; 34(2): 278-81, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26614584

ABSTRACT

BACKGROUND: We have found that there are usually 2 causes of acute dyspnea in our emergency department: (1) pulmonary infection only and (2) pulmonary infection in the setting of acute left ventricular heart failure (LVHF). These conditions are sometimes difficult to differentiate. Lung ultrasonography (LUS) is easily performed at the bedside and provides accurate information for diagnosis. In this study, we propose a simple B-line score to allow rapid differential diagnosis between these 2 lung conditions. METHODS: A prospective, single-blind trial was conducted on 98 patients with acute dyspnea in the emergency department. Lung ultrasonography and transthoracic echocardiography were performed within 30 minutes after enrollment. The final clinical diagnosis was recorded for all patients. Using the Bedside Lung Ultrasound in Emergency protocol, we recorded the number of B lines at 4 standardized points. Based on the theory of Lichtenstein, scores of 1, 2, 3, and 4 were categorized by the number of B lines on a static screen (0 to <3, 3 to <6, 6 to <8, and ≥8, respectively). The B-line score of 4 Bedside Lung Ultrasound in Emergency protocol points was recorded, and the total B-line score was calculated. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the rapid ultrasound measurements for the final clinical diagnosis. RESULTS: In our study, 27 patients were diagnosed with pulmonary infection and acute LVHF. The total number of B lines and the B-line score in patients with pulmonary infection in the setting of acute LVHF were 24.2±2.5 and 11.5±1.5, respectively, which were significantly higher than those in patients with pulmonary infection (12.5±6.4 and 7.2±1.9) (P=.000). In patients with pulmonary infection and acute LVHF, the effective diagnostic value of left ventricular ejection fraction and the total B-line score were similar (area under the ROC curve: 0.986 vs 0.962, P=.2607). The cutoff value of the total B-line score was 8, with a sensitivity of 80.7% and a specificity of 100%. A combination of LUS and echocardiography might improve the diagnostic accuracy (area under the ROC curve: 0.994; 95% confidence interval, 0.981-1.000; P=.000). CONCLUSIONS: This simple B-line score with LUS can help make a rapid differential diagnosis between pulmonary infection and pulmonary infection with acute LVHF. The diagnostic accuracy may be enhanced when used in conjunction with echocardiography.


Subject(s)
Respiratory Tract Infections/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Acute Disease , Aged , Diagnosis, Differential , Echocardiography , Emergency Service, Hospital , Female , Humans , Male , Prospective Studies , Respiratory Tract Infections/complications , Sensitivity and Specificity , Ventricular Dysfunction, Left/complications
11.
Yi Chuan ; 38(5): 418-26, 2016 05.
Article in Zh | MEDLINE | ID: mdl-27232490

ABSTRACT

Phytohormones are signaling molecules that control plant growth and development. Recent studies revealed that non-coding small RNAs play critical roles in plant development and stress responses via phytohormone signaling pathways. In this review, we summarize the present knowledge on the microRNAs (miRNAs) and secondary short interfering RNAs (siRNAs) involved in phytohormone signaling pathways, which include auxin, gibberellic acid, brassinosteroid and abscisic acid pathways. We also discuss their possible implications in phytohormone crosstalk during specific developmental processes.


Subject(s)
MicroRNAs/physiology , Plant Growth Regulators/physiology , RNA, Small Interfering/physiology , Signal Transduction/physiology , Animals , Humans , Plant Development
12.
Yi Chuan ; 38(7): 644-650, 2016 07 20.
Article in English | MEDLINE | ID: mdl-27733337

ABSTRACT

Autophagy is an evolutionarily highly conserved catabolic pathway among eukaryotic cells that protects the organisms against environmental stress. Normally, autophagy is mainly involved with autophagy-related proteins(ATGs) and autophagic regulators including a series of cytoplasmic proteins and small molecules. Besides, the selective autophagy, which targets damaged organalles or protein aggregates, is mediated by the additional receptors to help the ATGs recognize different substrates. In this review, we summarize recent advances in autophagic regulators like ROS(Reactive oxygen species), TOR(Target of rapamycin) and receptors like NBR1(Neighbor of BRCA1 gene protein), RPN10(Regulatory particle non-ATPase 10) as well as their functional mechanisms mainly in Arabidopsis thaliana.


Subject(s)
Autophagy , Plant Proteins/physiology , Arabidopsis Proteins/physiology , Carrier Proteins/physiology , Humans , Intracellular Signaling Peptides and Proteins , Proteins/physiology , TOR Serine-Threonine Kinases/physiology , Vesicular Transport Proteins/physiology
13.
Org Biomol Chem ; 13(23): 6449-52, 2015 Jun 21.
Article in English | MEDLINE | ID: mdl-25971529

ABSTRACT

The first example of arylboronic acid catalyzed [4 + 3] cycloaddition reaction is reported. 3,5-Bis-(trifluoromethyl) phenylboronic acid is shown to be the best catalyst in this reaction. The method has also enabled the preparation of cyclohepta[b]benzofurans and cyclohepta[b]indoles in excellent yields.

14.
Mol Biol Rep ; 42(2): 337-43, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25374427

ABSTRACT

We aimed to gain further insight into the role of the MAPK signaling pathway in terminal differentiation of normal human epidermal keratinocytes (NHEKs) with filaggrin knockdown. Filaggrin expression was knocked down by shRNA technology and the MAPK pathways were inhibited by three different inhibitors in NHEKs. The associated mRNAs and proteins were investigated by RT-PCR and western blot. Filaggrin absence inhibited the expression of differentiation-associated proteins, and blocked the protein expression of p38 MAPK, ERK1/2, JNK, Akt and NF-κB. Moreover, inhibited p38 MAPK, instead of ERK1/2 or JNK, lead to decreases in the expressions of Akt, NF-κB, and differentiation- associated proteins. In conclusion, Filaggrin might affect the epidermal terminal differentiation mainly through the p38-MAPK, NF-κB and Akt pathways. ERK1/2 and JNK might also be involved in the process.

15.
Zhonghua Yi Xue Za Zhi ; 95(34): 2791-5, 2015 Sep 08.
Article in Zh | MEDLINE | ID: mdl-26711980

ABSTRACT

OBJECTIVE: To evaluate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) with carotid atherosclerosis and the efficacy of continuous positive airway pressure (CPAP) treatment. METHODS: A total of 93 OSAHS patients diagnosed by polysomnography (PSG) were selected from Sleep Disorders Center at Affiliated Hospital of Xuzhou Medical College between March 2013 and December 2014. Based on the results of apnea-hypopnea index (AHI), they were divided into mild (n=22), moderate (n=37), and severe OSAHS group (n=34). Meanwhile, 28 healthy adult individuals matched for age and body mass index (BMI) were enrolled as the control group. The carotid intima-mesa thickness (IMT) was measured by color Doppler uhrasonography, and plasma levels of tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1) and nitric oxide (NO) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The correlations between carotid IMT and plasma levels of TNF-α, ET-1 and NO were analyzed. A total of 24 patients with moderate to severe OSAHS underwent CPAP treatment and the carotid IMT, plasma levels of TNF-α, ET-1 and NO were compared before and after CPAP treatment. RESULTS: OSAHS patients had significant increase of carotid IMT with the increasing disease severity, and the carotid IMT in mild, moderate and severe OSAHS groups were all significantly higher than that in the control group ((0.73 ± 0.31), (0.86 ± 0.07), (1.07 ± 0.14) vs (0.65 ± 0.10) mm, all P<0.05). The plasma levels of TNF-α and ET-1 in mild to severe OSAHS group were significantly higher than those in controls ((17.45 ± 3.02), (23.81 ± 2.91), (35.16 ± 3.43) vs (12.53 ± 3.48) ng/L and (0.81 ± 0.13), (1.06 ± 0.21), (1.66 ± 0.30) vs (0.64 ± 0.12) ng/L, all P<0.05 ), whereas plasma levels of NO in the three OSAHS groups were significantly decreased compared with the control group ((35.46 ± 10.12), (29.32 ± 9.47), (20.16 ± 7.41) vs (45.43 ± 7.92) µmol/L, all P<0.05). Furthermore, there were significant differences in plasma levels of TNF-α, ET-1 and NO among the three OSAHS groups (all P<0.05). Carotid IMT was positively correlated with plasma TNF-α and ET-1 (r=0.56 and 0.51) and negatively correlated with plasma NO (r=-0.46) (all P<0.05). After 3 months of CPAP treatment, plasma levels of TNF-α and ET-1 in OSAHS patients were significantly reduced ((19.64 ± 5.28), (0.94 ± 0.21) vs (28.72 ± 5.36), (1.36 ± 0.36) ng/L), and plasma NO was markedly increased ((33.57 ± 6.32) vs (24.34 ± 4.46) µmol/L, all P<0.05). However, CPAP treatment did not have a significant effect on carotid IMT ((0.91 ± 0.21) vs (0.96 ± 0.14) mm), P>0.05). CONCLUSIONS: Systemic inflammation and vascular endothelial dysfunction may play an important role in pathogenesis and development of carotid artery atherosclerosis in OSAHS. Short-term CPAP therapy alleviates systemic inflammation and improves endothelial function, but does not influence the increased carotid IMT in OSAHS patients.


Subject(s)
Atherosclerosis , Carotid Artery Diseases , Continuous Positive Airway Pressure , Sleep Apnea, Obstructive , Body Mass Index , Endothelin-1 , Enzyme-Linked Immunosorbent Assay , Humans , Inflammation , Nitric Oxide , Polysomnography , Tumor Necrosis Factor-alpha , Tunica Intima
16.
Cardiol Res ; 15(4): 262-274, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39205966

ABSTRACT

Background: Acute myocardial infarction (AMI) is a major cause of human health risk. Necroptosis is a newly and recently reported mode of cell death, whose role in AMI has not been fully elucidated. This study aimed to search for necroptosis biomarkers associated with the occurrence of AMI and to explore their possible molecular mechanisms through bioinformatics analysis. Methods: The dataset GSE48060 was used to perform weighted gene co-expression network analysis (WGCNA) and differential analysis. Key modules, differential genes, and necroptosis-related genes (NRGs) were intersected to obtain candidate biomarkers. Groups were classified and differentially analyzed according to the expression of the key biomarker. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and construction of protein-protein interaction (PPI) networks are performed on differentially expressed genes (DEGs). Finally, CIBERSORT was used to assess immune cell infiltration in AMI and the correlation of key biomarkers with immune cells. Immune cell infiltration analysis revealed the correlation between FASLG and multiple screened immune cells. Results: WGCNA determined that the MEsaddlebrown module was the most significantly associated with AMI. Intersecting it with DEGs as well as NRGs, we obtained two key genes, FASLG and IFNG. But only FASLG showed statistically significant differences between the AMI group and the normal control group. Further analysis suggested that the down-regulation of FASLG may exert its function through the regulation of the central genes CD247 and YES1. Furthermore, FASLG was positively correlated with T-cell CD4 memory activation and T-cell gamma delta, and negatively correlated with macrophage M0. Conclusion: In conclusion, FASLG and its regulatory genes CD247 and YES1 might be involved in the development of AMI by regulating immune cell infiltration. FASLG might be a potential biomarker for AMI and provides a new direction for the diagnosis of AMI.

17.
Huan Jing Ke Xue ; 45(7): 3881-3892, 2024 Jul 08.
Article in Zh | MEDLINE | ID: mdl-39022936

ABSTRACT

The spatio-temporal variation characteristics and potential sources of carbonaceous aerosols in the Guanzhong Plain during the Spring Festival in 2023 were analyzed using inverse distance weighting spatial interpolation (IDW), secondary organic carbon (SOC) estimation, and potential source contribution factor analysis (PSCF), with the OC and EC in the PM2.5 of five cities: Xi'an, Baoji, Xianyang, Weinan, and Tongchuan as the research objects. The results showed that in terms of time distribution, ρ(OC) was as follows: after the Spring Festival [(18.6 ±11.0) µg·m-3] > during the Spring Festival [(16.2 ±15.1) µg·m-3] > before the Spring Festival [(10.0 ±8.3) µg·m-3], and ρ(EC) was as follows: after the Spring Festival [(2.2 ±1.2) µg·m-3] > during the Spring Festival [(1.7 ±1.5) µg·m-3] > before the Spring Festival [(1.4 ±1.1) µg·m-3], which indicated that OC and EC concentrations were the most severe after the Spring Festival. In terms of spatial distribution, ρ(OC) was as follows: Xianyang [(21.4 ±17.3) µg·m-3] > Baoji [(15.8 ±12.8) µg·m-3] > Xi'an [(13.6 ±11.3) µg·m-3] > Weinan [(11.6 ±9.1) µg·m-3] > Tongchuan [(10.0 ±8.3) µg·m-3], and ρ(EC) was as follows: Xianyang [(2.1 ±1.4) µg·m-3] > Weinan [(1.8 ±1.4) µg·m-3] > Xi'an [(1.8 ±1.2) µg·m-3] > Tongchuan [(1.6 ±1.4) µg·m-3] > Baoji [(1.2 ±0.9) µg·m-3]. Overall, Xianyang had the most severe PM2.5 and carbon aerosol pollution, whereas Tongchuan had the least pollution. IDW results showed that the high-value center of OC and EC concentration [ρ(OC) > 27.3 µg·m-3, ρ(EC) > 2.9 µg·m-3] was in the middle of the plain, the low-value center of OC and EC concentration [ρ(OC) <7.0 µg·m-3, ρ(EC) < 1.0 µg·m-3] was in the northern plain, and the distribution of OC was higher in the west and lower in the east, whereas the distribution of EC was higher in the east and lower in the west. The proportion of SOC in OC was as follows: after the Spring Festival (51.7%) > during the Spring Festival (41.1%) > before the Spring Festival (36.8%). The SOC/OC values of each city and the contribution rate of SOC of each city to the Guanzhong Plain indicated that Tongchuan, Baoji, and Xianyang were greatly affected by the secondary conversion of organic carbon. The correlation of OC and EC before, during, and after the Spring Festival (r = 0.85, r = 0.98, and r = 0.94, respectively) indicated a high degree of homology between them. Carbonaceous aerosols had a certain correlation with humidity and wind speed before and during the Spring Festival but had a weak correlation with meteorological factors after the Spring Festival. Carbonaceous aerosols generally were strongly correlated with CO and NO2, and the correlation was strongest after the Spring Festival, whereas the correlation with SO2 was strongest during the Spring Festival. The potential source areas of carbonaceous aerosols in the five cities were mainly concentrated in the local and surrounding areas of southern Gansu, northern Shaanxi, and southern Shaanxi. They were also affected by long-distance transportation from the northwest before the Spring Festival.

18.
JMIR Public Health Surveill ; 10: e56283, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222341

ABSTRACT

BACKGROUND: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. OBJECTIVE: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. METHODS: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. RESULTS: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. CONCLUSIONS: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.


Subject(s)
Dust , Mining , Occupational Exposure , Silicon Dioxide , Silicosis , Humans , Silicosis/epidemiology , Silicosis/etiology , Occupational Exposure/adverse effects , Occupational Exposure/analysis , Occupational Exposure/statistics & numerical data , Silicon Dioxide/analysis , Silicon Dioxide/adverse effects , Dust/analysis , Male , China/epidemiology , Female , Risk Assessment/methods , Retrospective Studies , Mining/statistics & numerical data , Adult , Middle Aged , Cross-Sectional Studies , Cohort Studies
19.
Physiol Plant ; 148(4): 502-11, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23136980

ABSTRACT

The negative charges of cell wall pectin molecules attributed by pectin methylesterase (PME, EC 3.1.1.11) contribute to Al binding capacity. We examined the expression profiles of 35 members of the PME gene family in the root apex of an Al-sensitive rice 'Zhefu802' under Al stress. While root elongation was inhibited by 40% after 3-h exposure to 25 µM Al, cell wall PME activity and the abundance of eight PME genes transcripts were increased. The same Al treatment which had almost no effect on root elongation of an Al-resistant rice ssp. japonica 'Nipponbare' did not change the expression patterns of these eight PME genes. However, when Al concentration was increased to 50 µM, by which the root elongation of 'Nipponbare' was inhibited by 40% too, the expression of these PME genes were also upregulated except two genes with no signal. These suggest a possible correlation between the upregulated genes and Al-induced inhibition of root elongation in rice. Furthermore, these eight PME genes behaved differently when subjected to CdCl2 and LaCl3 treatments, implying the specificity of different PME genes in response to different metal toxicities. The transgenic rice overexpressing one of these eight PME genes OsPME14 showed higher PME activity and Al content in root tip cell wall, and became more sensitive to Al stress, verifying the involvement of the specific PME gene in Al toxicity. Therefore, our results provided the molecular evidence to connect the expression of specific PME genes with the Al-induced inhibition of root elongation in rice.


Subject(s)
Aluminum/toxicity , Carboxylic Ester Hydrolases/metabolism , Oryza/enzymology , Oryza/growth & development , Plant Roots/enzymology , Plant Roots/growth & development , Carboxylic Ester Hydrolases/genetics , Cell Wall/drug effects , Cell Wall/enzymology , Computational Biology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Plant/drug effects , Genes, Plant/genetics , Multigene Family , Oryza/drug effects , Oryza/genetics , Phenotype , Phylogeny , Plant Roots/drug effects , Plant Roots/genetics , Real-Time Polymerase Chain Reaction , Stress, Physiological/drug effects , Stress, Physiological/genetics
20.
Yi Chuan ; 35(11): 1274-82, 2013 Nov.
Article in Zh | MEDLINE | ID: mdl-24579310

ABSTRACT

Protein-protein interactions play key roles in the development of organisms and the response to biotic and abiotic stresses. Several wet-lab methods have been developed to study this challenging area,including yeast two-hybrid system, tandem affinity purification, Co-immunoprecipitation, GST Pull-down, bimolecular fluorescence complementation, fluorescence resonance energy transfer and surface plasmon resonance analysis. In this review, we discuss theoretical principles and relative advantages and disvantages of these techniques,with an emphasis on recent advances to compensate for limitations.


Subject(s)
Protein Interaction Mapping/trends , Proteins/metabolism , Animals , Humans , Protein Binding , Protein Interaction Mapping/methods , Proteins/genetics , Two-Hybrid System Techniques
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