RÉSUMÉ
Pyroptosis, a lytic and pro-inflammatory cell death, is important in various pathophysiological processes. Host- and bacteria-derived extracellular vesicles (EVs), as natural nanocarriers messengers, are versatile mediators of intercellular communication between different types of cells. Recently, emerging research has suggested that EVs exhibit multifaceted roles in disease progression by manipulating pyroptosis. This review focuses on new findings concerning how EVs shape disease progression in infectious and non-infectious diseases by regulating pyroptosis. Understanding the characteristics and activity of EVs-mediated pyroptotic death may conducive to the discovery of novel mechanisms and more efficient therapeutic targets in infectious and non-infectious diseases.
Sujet(s)
Vésicules extracellulaires , Pyroptose , Humains , Vésicules extracellulaires/métabolisme , Animaux , Maladies transmissibles/métabolisme , Maladies transmissibles/immunologieRÉSUMÉ
The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development Metabolite Bioanalysis Working Group on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from investigational new drug (IND) enabling studies, and phase I, phase II, and phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.
Sujet(s)
Développement de médicament , Rapport de recherche , HumainsRÉSUMÉ
To investigate the impact of the ethanoic fractions of Periploca forrestii Schltr. (P. forrestii) in ameliorating the liver injury caused by fluoride ingestion and to explore the potential mechanisms. Initially, an in vitro fluorosis cell model was constructed using the human normal liver cell line (L-02) induced by fluoride. Cell viability was assessed using the CCK-8 assay kit. The lactate dehydrogenase (LDH) assay kit was utilized to measure LDH content in the cell supernatant, while the malonic dialdehyde (MDA) assay kit was employed to determine MDA levels within the cells. Subsequently, a fluorosis rat model was established, and LDH content in the cell supernatant was measured using the LDH assay kit. Various parameters, including MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS) content within the cells, were detected using appropriate assay kits. Additionally, cell apoptosis rate was determined using the Annexin V-FITC/PI cell apoptosis assay kit. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 were analyzed through Western blotting. Compared to the model group, the ethanolic fraction D of P.forrestii (Fr.D) increased cell viability (P < 0.01) and decreased LDH and MDA levels (P < 0.01). In the high-dose Fr.D treatment group of fluoride-poisoned rats, serum ALT, AST, LDH and MDA levels significantly decreased (P < 0.01). Results from rat primary cells exhibited that the Fr.D administration group exhibited significantly higher cell survival rates than the fluoride group (P < 0.01). Similarly, primary rat cells treated with Fr.D showed enhanced cell viability (P < 0.05) and reduced apoptosis rate, LDH, MDA, SOD, GSH-Px, CAT, and ROS levels (P < 0.05) compared to the model group. Western blot analysis indicated that the Fr.D treatment group elevated the Bcl-2/Bax protein expression ratio and reduced Caspase-3 and Caspase-9 activation levels (P < 0.01) compared to the model group. The results suggest that components within the Fr.D from Periploca forrestii may alleviate fluoride-induced liver injury by potentially counteracting oxidative stress and cell apoptosis.
Sujet(s)
Periploca , Rats , Humains , Animaux , Espèces réactives de l'oxygène/métabolisme , Caspase-3/métabolisme , Caspase-9/métabolisme , Fluorures/toxicité , Fluorures/métabolisme , Foie/métabolisme , Apoptose , Protéines proto-oncogènes c-bcl-2/métabolisme , Superoxide dismutase/métabolisme , Stress oxydatifRÉSUMÉ
AIM:The aim of this study is to investigate the clinical utility of neutrophil gelatinase-associated lipocalin(NGAL)and other biomarkers in serum for patients with acute and chronic kidney injury.METHODS:A total of 171 patients with acute kidney injury(AKI)and 209 patients with chronic kidney disease(CKD)who sought medical care at the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou between January 2022 and July 2023 were in-cluded in this study.Data on potassium(K),sodium(Na),chloride(Cl),carbon dioxide(CO2),urea(Urea),and glu-cose(GLU)were collected from each group of participants.A total of 94 individuals who were deemed healthy and had un-dergone physical examinations within the same time frame were chosen as the control group.The serum NGAL levels of all three groups were measured using latex immunoturbidimetry.The diagnostic effectiveness of serum NGAL and other bio-markers in identifying acute and chronic kidney injury was analyzed.Multiple logistic regression equations were employed to examine the factors influencing the occurrence of AKI and CKD in patients.Additionally,receiver operating characteris-tic(ROC)curves were constructed to evaluate the clinical significance of these biomarkers in patients with kidney injury.RESULTS:Through bioinformatic analysis,it was suggested that NGAL may be a detection marker of kidney injury.Ac-cording to general data,in the AKI and the CKD groups,K,Na,CO2,Urea,GLU and NGAL levels were higher than those in the healthy control group(P<0.05).Multivariate logistic regression equation analysis showed that Na,Urea,GLU and NGAL levels were all independent risk factors for AKI or CKD disease occurrence(P<0.05).The ROC curve analysis showed that in the AKI group,the area under the curve(AUC)for Na,Urea,GLU and NGAL were 0.711,0.960,0.793 and 0.841,respectively(P<0.01).In the CKD group,the AUC for Na,Urea,GLU and NGAL were 0.681,0.990,0.703 and 0.930,respectively(P<0.01).The sensitivity and specificity of NGAL and Urea combined diagnosis for AKI were 81.9%and 61.1%,respectively,and those for CKD were 62.7%and 80.0%,respectively.CONCLUSION:Serum NGAL can serve as an indicator of acute and chronic kidney injury,and its combination with other biomarkers also has certain clinical application value in acute and chronic kidney injury.
RÉSUMÉ
This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.
Sujet(s)
Médicaments issus de plantes chinoises , Sialadénite , Syndrome de Gougerot-Sjögren , Humains , Syndrome de Gougerot-Sjögren/traitement médicamenteux , Facteur de nécrose tumorale alpha , Interleukine-6 , Simulation de docking moléculaire , Pharmacologie des réseaux , Inflammation/traitement médicamenteux , Bases de données génétiques , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/usage thérapeutiqueRÉSUMÉ
AIM: Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease. METHODS: Whole-genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network-based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves. RESULTS: We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS. CONCLUSION: Clinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.
Sujet(s)
Méthylation de l'ADN , Syndrome de Gougerot-Sjögren , Humains , Syndrome de Gougerot-Sjögren/diagnostic , Syndrome de Gougerot-Sjögren/génétique , Agranulocytes , Épigenèse génétique , Marqueurs biologiquesRÉSUMÉ
Tomato disease is an important disease affecting agricultural production, and the combined infection of tomato chlorosis virus (ToCV) and tomato yellow leaf curl virus (TYLCV) has gradually expanded in recent years, but no effective control method has been developed to date. Both viruses are transmitted by Bemisia tabaci Mediteranean (MED). Previously, we found that after B. tabaci MED was fed on ToCV-and TYLCV-infected plants, the transmission efficiency of ToCV was significantly higher than that on plants infected only with ToCV. Therefore, we hypothesize that co-infection could enhance the transmission rates of the virus. In this study, transcriptome sequencing was performed to compare the changes of related transcription factors in B. tabaci MED co-infected with ToCV and TYLCV and infected only with ToCV. Hence, transmission experiments were carried out using B. tabaci MED to clarify the role of cathepsin in virus transmission. The gene expression level and enzyme activity of cathepsin B (Cath B) in B. tabaci MED co-infected with ToCV and TYLCV increased compared with those under ToCV infection alone. After the decrease in cathepsin activity in B. tabaci MED or cathepsin B was silenced, its ability to acquire and transmit ToCV was significantly reduced. We verified the hypothesis that the relative expression of cathepsin B was reduced, which helped reduce ToCV transmission by B. tabaci MED. Therefore, it was speculated that cathepsin has profound research significance in the control of B. tabaci MED and the spread of viral diseases.
RÉSUMÉ
Four new xanthone glucosides, 3-hydroxy-2-methoxyxanthone-4-O-ß-D-glucopyranoside (1), 4,8-dihydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (2), 2-methoxyxanthone-5-O-ß-D-glucopyranoside (3), 4-hydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (4), a new phenolic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid monomethyl ester (5), and a new isoquinoline, methyl 6-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate (6) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR-ESI-MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. Compoundâ 2, 3 exhibited moderate inhibitory activity against NO production.
Sujet(s)
Hypericum , Hypericum/composition chimique , Fruit/composition chimique , Glucosides/composition chimique , Spectroscopie par résonance magnétiqueRÉSUMÉ
OBJECTIVE@#To explore the association between depressive symptoms and the risks of rapid decline in renal function and chronic kidney disease (CKD) in middle-aged and elderly with normal kidney function.@*METHODS@#The residents aged 40- 75 years with eGFR≥60 mL·min-1·1.73 m-2 without proteinuria in Lanzhou region, who participated in the "REACTION" study carried out in 2011, were selected and followed up in 2014. A total of 4961 individuals with complete and qualified data from the two surveys were included in the subsequent analysis. Based on PHQ-9 questionnaire scores, the baseline population was divided into two groups with and without depressive symptoms. Cox proportional hazard analysis was used to compare the incidences of rapid renal function decline and CKD between the two groups and study the association of depressive symptoms with the risk of these renal conditions.@*RESULTS@#PHQ-9 questionnaire scores were not found to correlate with baseline SCr, ALB, UACR or eGFR levels among the participarts (P>0.05). After a mean follow-up time of 3.4±0.6 years, 33.9% of the participants with depressive symptoms at baseline experienced a rapid decline in renal function and 3.6% progressed to CKD. During the follow-up, the incidence of rapid decline in renal function and the risk of developing CKD were not found to correlate with depressive symptoms in these participants (P>0.05) regardless of the type of the depressive syndromes.@*CONCLUSION@#Depressive symptoms are not associated with the risks of rapid renal function decline or progression to CKD in middle-aged and elderly with normal kidney function.
Sujet(s)
Sujet âgé , Adulte d'âge moyen , Humains , Études de cohortes , Dépression , Débit de filtration glomérulaire , Évolution de la maladie , Insuffisance rénale chronique/épidémiologie , Rein/physiologie , Facteurs de risqueRÉSUMÉ
Background There is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. Objective To explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. Methods The recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely <1 serving·week−1, 1-4 servings·week−1, and ≥5 servings·week−1. GDM was confirmed by oral glucose tolerance test (OGTT) between 24-28 weeks of gestation. A binary logistic regression model was applied to explore the association between SSB consumption and risk of GDM. Multiple linear regression was applied to investigate the associations between SSB consumption (per 1-serving·d−1 increase) and OGTT fasting plasma glucose, 1-hour glucose, and 2-hour glucose. Results A total of 3811 pregnant women were finally enrolled in this study, of which 752 developed GDM, with an incidence rate of 19.7%. The incidence rates of GDM in pregnant women with SSB consumption frequency of <1 serving·week−1, 1-4 servings·week−1, and ≥5 servings·week−1 were 18.0%, 21.1%, and 26.8%, respectively. After adjusting for maternal age, pre-pregnancy body mass index (BMI), education, number of children born, family history of diabetes, smoking, alcohol consumption, physical activity level, and total energy intake, the risk of GDM increased by 26% (OR=1.26, 95%CI: 1.05, 1.50) in the 1-4 servings·week−1 group and by 76% (OR=1.76, 95%CI: 1.31, 2.38) in the ≥5 servings·week−1 group compared to the <1 serving·week−1 SSB consumption group, respectively. Further stratified analysis revealed no interaction effect (Pinteraction>0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L−1 and 0.18 mmol·L−1, respectively (P<0.05), and no significant increase in fasting plasma glucose was found (P>0.05). Conclusion Higher SSB consumption before pregnancy increases the risk of GDM in pregnant women.
RÉSUMÉ
Objective: To analyze the incidence and survival rate of liver cancer cases in the entire population in the Qidong region from 1972 to 2019, so as to provide a basis for prognosis evaluation, prevention, and treatment. Methods: The observed survival rate (OSR) and relative survival rate (RSR) of 34 805 cases of liver cancer in the entire Qidong region population from 1972 to 2019 were calculated using Hakulinen's method with SURV3.01 software. Hakulinen's likelihood ratio test was used for statistical analysis. Age-standardized relative survival (ARS) was calculated using the International Cancer Survival Standard. The Joinpoint regression analysis was performed with Joinpoint 4.7.0.0 software to calculate the average annual percentage change (AAPC) of the liver cancer survival rate. Results: 1-ASR increased from 13.80% in 1972-1977 to 50.20% in 2014-2019, while 5-ASR increased from 1.27% in 1972-1977 to 27.64% in 2014-2019. The upward trend of RSR over eight periods was statistically significant (χ (2) = 3045.29, P < 0.001). Among them, male 5-ASR was 0.90%, 1.80%, 2.33%, 4.92%, 5.43%, 7.05%, 10.78%, and 27.78%, and female 5-ASR was 2.33%, 1.51%, 3.35%, 3.92%, 3.84%, 7.18%, 11.45%, and 29.84%, respectively. There was a statistically significant difference in RSR between males and females (χ (2) = 45.68, P < 0.001). The 5-RSR for each age group of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 4.92%, 5.29%, 8.17%, 11.70%, 11.63%, and 9.60%, respectively. There were statistically significant differences in RSR among different age groups (χ (2) = 501.29, P < 0.001). The AAPC in Qidong region from 1972 to 2019 for 1-ARS, 3-ASR, and 5-ARS were 5.26% (t = 12.35, P < 0.001), 8.10% (t = 15.99, P < 0.001), and 8.96 % (t = 16.06, P < 0.001), respectively. The upward trend was statistically significant in all cases. The AAPC of 5-ARS was 9.82% in males (t = 14.14, P < 0.001), and 8.79% in females (t = 11.48, P < 0.001), and the upward trend was statistically significant in both. The AAPC of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 5.37% (t = 5.26, P = 0.002), 5.22% (t = 5.66, P = 0.001), 7.20% (t = 6.88, P < 0.001), 10.00% (t = 12.58, P < 0.001), 9.96% (t = 7.34, P < 0.001) and 8.83% (t = 3.51, P = 0.013), and the upward trend was statistically significant. Conclusion: The overall survival rate of registered cases of liver cancer in the Qidong region's entire population has greatly improved, but there is still much room for improvement. Hence, constant attention should be paid to the study on preventing and treating liver cancer.
Sujet(s)
Mâle , Humains , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Taux de survie , Tumeurs du foie/épidémiologie , Pronostic , Incidence , Logiciel , Chine/épidémiologieRÉSUMÉ
Gukang Capsules are often used in combination with drugs to treat fractures, osteoarthritis, and osteoporosis. Cytochrome P450(CYP450) mainly exists in the liver and participates in the oxidative metabolism of a variety of endogenous and exogenous substances and serves as an important cause of drug-metabolic interactions and adverse reactions. Therefore, it is of great significance to study the effect of Gukang Capsules on the activity and expression of CYP450 for increasing its clinical rational medication and improving the safety of drug combination. In this study, the Cocktail probe method was used to detect the changes in the activities of CYP1A2, CYP3A2, CYP2C11, CYP2C19, CYP2D4, and CYP2E1 in rat liver after treatment with high-, medium-and low-dose Gukang Capsules. The rat liver microsomes were extracted by the calcium chloride method, and protein expression of the above six CYP isoform enzymes was detected by Western blot. The results showed that the low-dose Gukang Capsules could induce CYP3A2 and CYP2D4 in rats, medium-dose Gukang Capsules had no effect on them, and high-dose Gukang Capsules could inhibit them in rats. The high-dose Gukang Capsules did not affect CYP2C11 in rats, but low-and medium-dose Gukang Capsules could induce CYP2C11 in rats. Gukang Capsules could inhibit CYP2C19 in rats and induce CYP1A2 in a dose-independent manner, but did not affect CYP2E1. If Gukang Capsules were co-administered with CYP1A2, CYP2C19, CYP3A2, CYP2C11, and CYP2D4 substrates, the dose should be adjusted to avoid drug interactions.
Sujet(s)
Cytochrome P-450 CYP1A2 , Cytochrome P-450 CYP2E1 , Rats , Animaux , Cytochrome P-450 CYP1A2/métabolisme , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP2E1/métabolisme , Cytochrome P-450 CYP2E1/pharmacologie , Rat Sprague-Dawley , Cytochrome P-450 enzyme system/génétique , Cytochrome P-450 enzyme system/métabolisme , Microsomes du foie , Foie , Cytochrome P-450 CYP3A/métabolismeRÉSUMÉ
BACKGROUND: Snail control is critical to schistosomiasis control efforts in China. However, re-emergence of Oncomelania hupensis is challenging the achievements of schistosomiasis control. The present study aimed to test whether the amphibious snails can spread across watersheds using a combination of population genetics and geographic statistics. METHODS: The digital maps and attributes of snail habitats were obtained from the national survey on O. hupensis. Snail sampling was performed in 45 counties of Sichuan Province. The cox1 gene of specimens was characterized by sequencing. Unique haplotypes were found for phylogenetic inference and mapped in a geographical information system (GIS). Barriers of gene flow were identified by Monmonier's maximum difference algorithm. The watercourses and watersheds in the study area were determined based on a digital elevation model (DEM). Plain areas were defined by a threshold of slope. The slope of snail habitats was characterized and the nearest distance to watercourses was calculated using a GIS platform. Spatial dynamics of high-density distributions were observed by density analysis of snail habitats. RESULTS: A total of 422 cox1 sequences of O. hupensis specimens from 45 sampling sites were obtained and collapsed into 128 unique haplotypes or 10 clades. Higher haplotype diversity in the north of the study area was observed. Four barriers to gene flow, leading to five sub-regions, were found across the study area. Four sub-regions ran across major watersheds, while high-density distributions were confined within watersheds. The result indicated that snails were able to disperse across low-density areas. A total of 63.48% habitats or 43.29% accumulated infested areas were distributed in the plain areas where the overall slope was < 0.94°. Approximately 90% of snail habitats were closer to smaller watercourses. Historically, high-density areas were mainly located in the plains, but now more were distributed in hilly region. CONCLUSIONS: Our study showed the cross-watershed distribution of Oncomelania snails at a large scale. Natural cross-watershed spread in plains and long-distance dispersal by humans and animals might be the main driver of the observed patterns. We recommend cross-watershed joint control strategies for snail and schistosomiasis control.
Sujet(s)
Gastropoda , Schistosomiase , Animaux , Chine/épidémiologie , Écosystème , Humains , Phylogenèse , Schistosoma , Schistosomiase/épidémiologieRÉSUMÉ
In the present study, we investigate the regeneration efficiency of Rhodamine B (RhB)-saturated granular activated carbon (GAC) in an electrochemical regeneration system by using a 9,10-anthraquinone-2-sulfonic acid/polypyrrole modified graphite plate (AQS/PPy-GP) cathode. The response surface methodology based on the Box-Behnken design (RSM-BBD) approach was used to optimize regeneration parameters, whereby the optimum condition of the independent variables was as follows: applied current = 155 mA, concentration of supporting electrolyte = 0.13 M, and regeneration time = 7 h. The electrochemical regeneration system with the AQS/PPy-GP electrode achieved high regeneration efficiency and significantly reduced energy consumption. H2O2 concentration generated in the electrolysis system was notably increased, and the time of complete degradation of organics was shortened by 25% compared to the electrode without modification. The mechanism for RhB degradation was proposed as AQS acting as a catalyst to promote the formation of H2O2. The regeneration study showed that AQS/PPy-GP cathode had appreciable reusability for GAC regeneration with a regeneration efficiency of 76.6% after 8 regeneration cycles. In summary, the electrochemical regeneration based on AQS/PPy-GP cathode would have practical industrial applications in treating spent activated carbons.
Sujet(s)
Graphite , Anthraquinones , Charbon de bois , Électrodes , Peroxyde d'hydrogène , Polymères , PyrrolesRÉSUMÉ
OBJECTIVE: Severe pneumonia occurs commonly in children and is the main cause of clinical infant mortality. This study tested the expression pattern of long noncoding RNA cancer susceptibility candidate 2 (CASC2) in the serum of children with severe pneumonia and explored its clinical values. METHODS: Serum levels of CASC2 were detected in 145 children with severe pneumonia. All cases were divided into two groups based on their respiratory failure (RF) condition. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves were plotted for the diagnostic and prognostic ability evaluation. Multivariate cox regression analysis was done for the examination of independent influence factors. RESULTS: The serum levels of CASC2 significantly decreased in children with severe pneumonia in contrast with healthy individuals and reached the lowest value in those with RF. Serum CASC2 can distinguish severe pneumonia and predicted the development of RF. Based on the 28-day survival data, cases with low CASC2 levels had a poor survival rate. CASC2 (hazard ratio [HR] = 0.068, 95% confidence interval [CI] = 0.016-0.292, P < 0.001) and age (HR = 2.806, 95% CI = 1.240-6.394, P < 0.001) were independent influence factor for the poor prognosis of children with severe pneumonia. CONCLUSION: Downregulation of serum CASC2 was related to the occurrence of RF in children with severe pneumonia and may be a predictor of the poor prognosis. This study will provide a potential biomarker for severe pneumonia treatment in clinic.
Sujet(s)
Tumeurs , Pneumopathie infectieuse , ARN long non codant , Insuffisance respiratoire , Protéines suppresseurs de tumeurs/génétique , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Enfant , Humains , Pneumopathie infectieuse/complications , Pneumopathie infectieuse/génétique , ARN long non codant/génétique , Insuffisance respiratoire/génétiqueRÉSUMÉ
Background: Shenxiong Glucose Injection (SGI) is a traditional Chinese medicine formula composed of ligustrazine hydrochloride and Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae). Our previous studies and others have shown that SGI has excellent therapeutic effects on myocardial ischemia (MI). However, the potential mechanisms of action have yet to be elucidated. This study aimed to explore the molecular mechanism of SGI in MI treatment. Methods: Sprague-Dawley rats were treated with isoproterenol (ISO) to establish the MI model. Electrocardiograms, hemodynamic parameters, echocardiograms, reactive oxygen species (ROS) levels, and serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were analyzed to explore the protective effect of SGI on MI. In addition, a model of oxidative damage and apoptosis in human umbilical vein endothelial cells (HUVECs) was established using CoCl2. Cell viability, Ca2+ concentration, mitochondrial membrane potential (MMP), apoptosis, intracellular ROS, and cell cycle parameters were detected in the HUVEC model. The expression of apoptosis-related proteins (Bcl-2, Caspase-3, PARP, cytoplasmic and mitochondrial Cyt-c and Bax, and p-ERK1/2) was determined by western blotting, and the expression of cleaved caspase-3 was analyzed by immunofluorescence. Results: SGI significantly reduced ROS production and serum concentrations of cTnI and cTnT, reversed ST-segment elevation, and attenuated the deterioration of left ventricular function in ISO-induced MI rats. In vitro, SGI treatment significantly inhibited intracellular ROS overexpression, Ca2+ influx, MMP disruption, and G2/M arrest in the cell cycle. Additionally, SGI treatment markedly upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins p-ERK1/2, mitochondrial Bax, cytoplasmic Cyt-c, cleaved caspase-3, and PARP. Conclusion: SGI could improve MI by inhibiting the oxidative stress and apoptosis signaling pathways. These findings provide evidence to explain the pharmacological action and underlying molecular mechanisms of SGI in the treatment of MI.
RÉSUMÉ
The present study investigated the effects of ligustrazine hydrochloride(LH)-Salviae Miltiorrhizae Radix et Rhizoma(SM) before and after compatibility on the pharmacokinetics of acute myocardial ischemia(AMI) rats and revealed the mechanism of pharmacokinetic changes from the perspective of metabolic enzymes. AMI rats underwent single injection of SM Glucose Injection, LH Glucose Injection, and LH-SM Glucose Injection in the caudal vein, respectively(3.78 mg·kg~(-1) salvianic acid, 0.049 mg·kg~(-1) rosmarinic acid, and 13.68 mg·kg~(-1) ligustrazine). Blood samples were collected from the orbital venous plexus at different time points, and the liver of the rats was removed after the last blood sampling. The plasma concentrations of salvianic acid, rosmarinic acid, and ligustrazine were detected by UPLC-MS/MS. Western blot was used to detect the protein expression of CYP1 A2, CYP2 C11, CYP2 C19, CYP2 D4, CYP2 E1, and CYP3 A2 in the liver of rats in each group. As revealed by the pharmacokinetic results, compared with the LH Glucose Injection group, the LH-SM Glucose Injection group showed a downward trend of T_(1/2) of ligustrazine in AMI rats and decreased AUC(P<0.05). Compared with the SM Glucose Injection, there were no significant differences in the pharmacokinetic parameters of salvianic acid and rosmarinic acid in the LH-SM Glucose Injection group. Protein expression results showed that the expression levels of CYP1 A2, CYP2 C11, CYP2 D4, CYP2 E1, and CYP3 A2 in the LH-SM Glucose Injection group increased(P<0.05) and the expression level of CYP2 C19 decreased(P<0.05) compared with those in the LH Glucose Injection group. CYP1 A2, CYP2 C11, and CYP3 A2 are isoenzymes involved in ligustrazine â metabolism. When LH and SM were used in combination, the expression of these three enzymes increased, which changed the pharmacokinetic process in rats and accelerated the metabolism of ligustrazine.
Sujet(s)
Médicaments issus de plantes chinoises , Salvia miltiorrhiza , Rats , Animaux , Chromatographie en phase liquide , Spectrométrie de masse en tandem , Cytochrome P-450 enzyme system ,RÉSUMÉ
Objective: To describe the epidemic characteristics of stomach cancer mortality in Qidong between 1972 and 2016. Methods: The cancer registry data of stomach cancer death and population during 1972-2016 in Qidong was collected. The mortality of crude rate (CR), China age-standardized rate (CASR), world age-standardized rate (WASR), 35-64 years truncated rate, 0-74 years cumulative rate, cumulative risk, percentage change (PC), annual percent change (APC) were calculated. Results: During 1972-2016, a total of 15 863 (male: 10 114, female: 5 749) deaths occurred attributed to stomach cancer, accounting for 16.04% of all cancers, with CR of 31.37/100 000 (CASR: 12.97/100 000, WASR: 21.39/100 000). The truncated rate of 35-64, cumulative rate of 0-74, and cumulative risk were 28.86/100 000, 2.54%, and 2.51%, respectively. For male, the CR, CASR, WASR were 40.53/100 000, 17.98/100 000, 30.13/100 000, respectively, and for female, the CR, CASR, WASR were 22.45/100 000, 8.52/100 000, 13.92/100 000, respectively. Age-specific mortality analysis showed that the mortality of each age group under 25-year-old group was less than 1/100 000. The CR increased with age. The 50-year-old group reached and exceeded the average mortality of the population, and more than 80-year-old group reached the peak of death. During 1972-2016 in Qidong, The PCs in CR, CASR, and WASR of stomach cancer were 55.43%, -52.02%, -43.60%. The APC were 0.54%, -2.30%, -2.08%, respectively. Period mortality analysis showed that except for the 75-year-old group, the mortality of stomach cancer decreased significantly. Conclusions: The crude mortality of stomach cancer increases slightly in Qidong, while the CASR and WASR decrease significantly. However, stomach cancer is still one of the malignant tumors that most affect health and seriously threat lives.
Sujet(s)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Chine/épidémiologie , Incidence , Enregistrements , Tumeurs de l'estomac/épidémiologieRÉSUMÉ
OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.