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This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.
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Objective:To investigate the mechanisms underlying the effect of levocarnitine on myocardial cell fibrosis, proliferation, apoptosis and migration.Methods:Between June and December 2022, an overexpression vector for tissue inhibitor-1 of metalloproteinase(TIMP-1)and siRNA TIMP-1 were used to transfect rat H9c2 cardiomyocytes(from the cell bank of the Chinese Academy of Sciences), and transfection efficiency was measured using fluorescence reverse transcription quantitative PCR(RT-qPCR). After treating H9c2 cells with angiotensin Ⅱ(AngⅡ), the expression of the MMP3 and TIMP-1 genes in the cells was detected by RT-qPCR.A CCK8 kit was used to assess the effect of levocarnitine intervention on the proliferation of myofibroblasts after overexpression or knockdown of TIMP-1.The effects of levocarnitine on apoptosis and migration of myofibroblasts were detected by flow cytometry and Transwell assays.Results:The RT-qPCR results showed that the expression level of the MMP3 gene(1.38±0.05)in cardiomyocytes treated with AngⅡ for 24 hours exhibited an upward trend( P<0.01), while the expression level of the TIMP-1 gene(0.71±0.03)showed a downward trend( P<0.01). In addition, H9c2 cells with TIMP-1 overexpression(905.98±24.17)and knockdown(0.18±0.01)%, respectively, were successfully constructed.Based on CCK-8 detection results, knockdown of TIMP-1(86.56±7.98)% was able to promote the proliferation of H9c2 cells induced by levocarnitine( P<0.01). Apoptosis experiments showed that inhibition of TIMP-1 expression(23.22±2.69)significantly reduced the apoptosis level of H9c2 cells induced by levocarnitine( P<0.01). Migration experiments showed that inhibition of TIMP-1 expression(217.67±23.44)significantly promoted the migration ability of H9c2 cells induced by levocarnitine( P<0.01). Conclusions:After intervention to reduce TIMP-1 expression, levocarnitine can promote proliferation, inhibit apoptosis and promote migration of myofibroblasts and may therefore ameliorate myocardial fibrosis.
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HHIP gene encoded human hedgehog-interacting protein,locating on chromosome 4q31.21-31.3.As an endogenous antagonist of Hedgehog(Hh)signaling pathway,HHIP inhibits the activation of Hh signaling pathway.In human cancers,the Hh signaling pathway has always been abnormally activated,and HHIP expression is generally down-regulated in most types of tumor tissues.The expression level of HHIP is positively correlated with overall survival of tumor patients,which is expected to be used as an independent prognostic marker.This review focused on the progress of HHIP research regarding its biological function,mechanism,and clinical value in tumor.
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Objective:To investigate the regulation of melatonin(MT)against lung injury in a mouse model of influenza virus infection by regulating the maternally expressed gene 3(MEG3)/microRNA-223(miR-223)/nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)axis.Methods:Fifty mice were randomly divided into control group,model group,and MT(low,medium,and high)dose groups,with 10 mice in each group.Except for the control group,the other groups were given H7N9 virus suspension nasal drops at a dose of 5×105 EID50,and the control group was given an equal volume of phosphate buffer nasal drops.The MT(low,medium,and high)dose groups were injected intraperitoneally with(15,30,60)mg/kg MT on the day after modeling,the control group and model group were intraperitoneally injected with equal volume of normal saline.The mice were sacri-ficed 24 h after the last administration for experiment.All mice were tested for the lung index;Hematoxylin-Eosin(HE)staining was used to observe the lung tissue morphology;ELISA was used to detect the levels of interleukin IL-1β,IL-18,IL-6,TNF-α and IFN-β in lung tissues;real-time fluorescent quantitative PCR(RT-qPCR)was used to detect the levels of MEG3 mRNA and miR-223 in mouse lung tissues;Western blot was used to detect the protein levels of NLRP3,apoptosis-related dot-like protein(ASC),cysteine aspartate proteolytic enzyme 1(caspase-1),and pro-caspase-1 in lung tissues.Bioinformatics prediction and dual luciferase experi-ments were used to detect the targeting relationship between MEG3 and miR-223,miR-223 and NLRP3.Results:The pathological re-sults showed that the alveolar wall of the lung tissue of the model group was obviously congested,and there was obvious inflammatory exudation and inflammatory cell infiltration in the cavity;with the increase of the MT dose,the hyperemia of the alveolar wall of the mouse lung tissue,the inflammatory exudation in the cavity and the infiltration of inflammatory cells in the MT(low,medium,and high)dose group were all improved.Compared with control group,the lung index,chemokines,inflammatory factors,antiviral fac-tors,MEG3 levels in lung tissues,NLRP3 pathway protein level in the model group were increased(P<0.05),and the miR-223 level was decreased(P<0.05);after the addition of MT,the antiviral factors increased significantly,and other indicators were improved.miR-223 had targeted regulatory relationships with MEG3 and NLRP3.Conclusion:MT can alleviate the lung injury of H7N9 influen-za virus-infected mice,which may be related to the regulation of MEG3/miR-223/NLRP3 axis to relieve inflammation.
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OBJECTIVE@#This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 μg/L maintained through sustainable universal salt iodization.@*METHODS@#This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits.@*RESULTS@#The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5-198.1 μg/L) in the counties with an mUIC of 100-149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5-244.4 μg/L) in the counties with an mUIC of 150-249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken.@*CONCLUSION@#Compared with an mUIC of 150-249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China.
Subject(s)
Female , Humans , Pregnancy , Cross-Sectional Studies , Iodine/urine , Pregnant Women , Sodium Chloride, Dietary , Thyroglobulin , Thyroid Gland , Thyrotropin , East Asian PeopleABSTRACT
Objective:To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa.Methods:A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared.Results:(1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95% CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 ( P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 ( P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion ( P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions:In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.
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It was a retrospective study. The patients with type 2 diabetes mellitus (T2DM) who underwent renal biopsy in the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2021 were enrolled to analyze the pathological and clinical manifestations of kidney. There were 483 patients enrolled, including 136 patients who had no history of diabetes mellitus, newly diagnosed as T2DM according to an oral glucose tolerance test. The age was (52.80±13.13) years old. There were 337 males (69.77%). Based on the renal biopsy, the patients were classified as diabetic kidney disease (DKD, 22.15%, 107/483), DKD+non-diabetic kidney disease (NDKD)(6.63%, 32/483), and NDKD (71.22%, 344/483). Membranous nephropathy was the most common pathology in patients with NDKD (40.41%, 139/344) and DKD+NDKD (34.38%, 11/32). In the 136 newly diagnosed T2DM patients, there were 3 patients (2.21%) with DKD, 2 patients (1.47%) with DKD+NDKD, and 131 patients with NDKD (96.32%). The proportions of DKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 10.53% (6/57), 25.00% (16/64), 26.53% (26/98), 41.56% (32/77) and 47.06% (24/51), respectively. The proportions of DKD+NDKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 3.51% (2/57), 3.13% (2/64), 10.20% (10/98), 9.09% (7/77) and 17.65% (9/51), respectively. Multivariate logistic regression analysis results showed that, the duration of diabetes history ( OR=1.130, 95% CI 1.057-1.208, P<0.001), diabetes retinopathy ( OR=12.185, 95% CI 5.331-27.849, P<0.001), urinary red blood cell count ( OR=0.987, 95% CI 0.974-0.999, P=0.039), glycosylated hemoglobin ( OR=1.482, 95% CI 1.119-1.961, P=0.006) as well as hemoglobin ( OR=0.973, 95% CI 0.957-0.990, P=0.001) were independently correlated with DKD. The proportions of DKD and DKD+NDKD increase with the prolongation of diabetes history. Membranous nephropathy is the most common pathology in NDKD and DKD+NDKD patients. Even in patients newly diagnosed with T2DM, it is necessary to screen for DKD. The duration of diabetes history, diabetes retinopathy, urinary red blood cell count, glycosylated hemoglobin and hemoglobin may be used to identify DKD from NDKD.
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A patient with SARS-CoV-2 infection was adimitted to Shanghai Shibei hospital of Jing'an District in early 2023. According to the patient's complaits, clinical manifestations, physical symptoms, laboratory examination, radiological image results, plus lumbar puncture, the patient was diagnosed with novel coronavirus encephalitis. The patient was discharged from the hospital after a combined treatment of Chinese and western medicine.
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To explore the relationship between the early or delayed age at natural menopause and metabolic syndrome (MS) in women. A total of 4 734 natural menopausal women who completed the baseline survey from November 2017 to January 2020 in the Guangzhou Middle-aged and Elderly Chronic Disease Prospective Cohort Study were selected in this cross-sectional study. Data on general demographic characteristics, disease history and female physiological health indicators were collected. Logistic regression model and restricted cubic spline curve were used to analyze the relationship between the age at natural menopause and MS. The results showed that the mean age of the subjects was (60±6) years old. The median (Q1,Q3) age at natural menopause was 50 (49, 52) years old, and the prevalence of MS was 14.8%(699/4 734). After adjusting for confounders, the age at natural menopause was closely related to MS in an approximate"U"shape. Compared with the group of normal age at natural menopause, the early age at menopause (OR=1.52, 95%CI: 1.12-2.06) and delayed age at menopause (OR=1.77, 95%CI: 1.36-2.30) had a higher risk of MS. In the group with time since menopause ≤6 years and 7-9 years, the risk of MS in the group with delayed age at menopause was 2.40 times (95%CI: 1.54-3.75) and 2.19 times (95%CI: 1.11-4.31) higher than that in the group with normal menopausal age, respectively. In conclusion, the early and delayed age at natural menopause increased the risk of MS. The increased risk of MS in delayed age at natural menopause mainly occurred within 10 years since menopause.
Subject(s)
Middle Aged , Aged , Female , Humans , Child , Postmenopause , Metabolic Syndrome/epidemiology , Prospective Studies , Cross-Sectional Studies , Menopause/physiology , Risk FactorsABSTRACT
The ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to conduct the qualitative analysis of the monoterpene chemical components from Paeoniae Radix Rubra. Gradient elution was performed on C_(18) HD(2.1 mm×100 mm, 2.5 μm) column with a mobile phase of 0.1% formic acid(A) and acetonitrile(B). The flow rate was 0.4 mL·min~(-1) and the column temperature was 30 ℃. MS analysis was conducted in both positive and negative ionization modes using electrospray ionization(ESI) source. Qualitative Analysis 10.0 was used for data processing. The identification of chemical components was realized by the combination of standard compounds, fragmentation patterns, and mass spectra data reported in the literature. Forty-one monoterpenoids in Paeoniae Radix Rubra extract were identified. Among them, 8 compounds were reported in Paeoniae Radix Rubra for the first time and 1 was presumed to be the new compound 5″-O-methyl-galloylpaeoniflorin or its positional isomer. The method in this study realizes the rapid identification of monoterpenoids from Paeoniae Radix Rubra and provides a material and scientific basis for quality control and further study on the pharmaceutical effect of Paeoniae Radix Rubra.
Subject(s)
Chromatography, Liquid , Drugs, Chinese Herbal , Mass Spectrometry , MonoterpenesABSTRACT
Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.
Subject(s)
Rats , Animals , Matrix Metalloproteinase 9/metabolism , NF-E2-Related Factor 2/metabolism , Tight Junction Proteins/metabolism , Occludin/pharmacology , Choroid Plexus/metabolism , Reactive Oxygen Species/metabolism , Lanthanum/pharmacology , Epithelial Cells , Zonula Occludens-1 Protein/metabolism , Phosphoproteins/pharmacologyABSTRACT
Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Subject(s)
Humans , Enterotoxins/genetics , Superantigens/genetics , Catalytic Domain , Selenoprotein W/metabolism , Receptors, Antigen, T-CellABSTRACT
Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.
Subject(s)
Humans , Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Multilocus Sequence Typing , Phylogeny , Staphylococcal Infections/epidemiology , China/epidemiologyABSTRACT
Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Subject(s)
Humans , Mice , Rats , Cell Proliferation , Heart/physiology , Mammals , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Pericardium/metabolism , Single-Cell Analysis , Zebrafish/metabolismABSTRACT
Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination
Subject(s)
Animals , Male , Rats , Arthritis, Experimental/chemically induced , Therapeutic Uses , Enzyme-Linked Immunosorbent Assay/methods , Dinoprostone/adverse effects , Interleukin-6/pharmacology , Interleukin-1/pharmacology , Interleukin-10/pharmacology , Matrix Metalloproteinases , Microscopy, Electron, Transmission/methodsABSTRACT
@#Abstract:Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Long-term alcoholism causes a series of pathological changes in the liver, which eventually leads to the occurrence of liver diseases with an increasing incidence. At present, significant progress has been made in the pathogenesis and pathological development of alcoholic liver disease, but the relevant mechanism of ALD has not been thoroughly studied. It is necessary to improve the existing animal model or establish a new, more comprehensive animal ALD model to simulate human ALD. Experimental animal models of ALD, especially rodents, are often used to simulate human ALD, and the ideal rodent ALD model can effectively simulate all aspects of alcohol in human liver. But so far, the commonly used animal models all have certain defects, and there is no complete animal model that can simulate human ALD. This paper reviewed the pathogenesis of ALD, related methods and influencing factors of ALD model, and provided a theoretical basis for relevant researchers to establish the ALD rodent model.
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【Objective】 To explore the psychological experience of blood donors with blood donation-related vasovagal reaction (DRVR), so as to provide basis for improving the quality of blood donation services. 【Methods】 The real experience of 9 DRVR blood donors was analyzed using the phenomenological research method in qualitative research. 【Results】 The occurrence of DRVR caused distinct psychological conflict among blood donor. Blood donors lacked knowledge about blood donation and expected professional evaluation and continuous support. The occurrence of DRVR was an important reason for blood donor lapsing. 【Conclusion】 By resolving the distinct psychological conflicts of DRVR blood donors, establishing DRVR early warning evaluation and feedback system, as well as strengthening the construction of support system, blood collection and supply institutions can create a good humanistic and social environment for sustainable development of voluntary blood donation.
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Objective:To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester.Methods:A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared.Results:Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta ( P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95% CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness ( OR=0.033, 95% CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions:(1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.
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Objective @#To analyze the trend of lung cancer incidence in Shaoxing, Zhejiang Province from 2014 to 2019, so as to provide the basis for lung cancer prevention and control.@*Methods @#The data of lung cancer were collected through the information management system of chronic disease surveillance in Zhejiang Province.The crude incidence rate, age-standardized incidence rates by Chinese standard population ( ASIRC ) and by world standard population ( ASIRW ), truncated rate ( 35-64 ) years old ), and cumulative rate (0-74 years old) were calculated. The annual percentage change ( APC ) was used to analyze the trend of lung cancer. The annual contribution rate was used to analyze the contribution of the incidence trend with age to the total trend. @*Results @#Totally 22 261 cases of lung cancer were reported in Shaoxing from 2014 to 2019. The crude incidence rate, ASIRC, ASIRW, truncated rate ( 35-64 years old ), and cumulative rate ( 0-74 years old ) were 83.51/100 000, 41.28/100 000, 41.01/100 000, 57.00/100 000 and 5.11%, respectively. The crude incidence rate, ASIRC and ASIRW increased significantly from 2014 to 2019, with the APC values of 8.56%, 6.42% and 6.05%, respectively ( P<0.05 ). The crude incidence rate, ASIRC, ASIRW, truncated rate ( 35-64 years old ), and cumulative rate ( 0-74 years old ) of man were 105.25/100 000, 48.09/100 000, 50.69/100 000, 62.03/100 000 and 6.42%, respectively, which were higher than those of women ( 61.84/100 000, 33.05/100 000, 31.35/100 000, 51.71/100 000 and 3.76% ).The crude incidence rate increased with age. The annual contribution rates of lung cancer incidence in people aged 15-<45 years, 45-<55 years, 55-<65 years and ≥65 years were 51.20%, 30.86%, 15.79% and 2.15%, respectively. The crude incidence rate in people aged 15-<45 years, 45-<55 years and 55-<65 years increased significantly from 2014 to 2019, with the APC values of 23.84%, 13.79% and 6.78%, respectively ( P<0.05 ). @*Conclusion @#From 2014 to 2019, the incidence of lung cancer in Shaoxing shows an increasing trend, and the age of onset is getting younger.
ABSTRACT
OBJECTIVE@#To investigate the changes in function of CD8@*METHODS@#Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8@*RESULTS@#The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8@*CONCLUSION@#The exhausted CD8