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Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.
Subject(s)
Aortic Valve Stenosis , Heart Failure , MicroRNAs , Animals , Mice , Cardiomegaly/genetics , Glucagon-Like Peptide 1 , MicroRNAs/genetics , Cystathionine gamma-LyaseABSTRACT
Plenty of freshwater species, especially macroinvertebrates that are essential to the provision of numerous ecosystem functions, encounter higher mortality due to acute hypoxia. However, within the family Chironomidae, a wide range of tolerance to hypoxia/anoxia is displayed. Propsilocerus akamusi depends on this great tolerance to become a dominant species in eutrophic lakes. To further understand how P. akamusi responds to acute hypoxic stress, we used multi-omics analysis in combination with histomorphological characteristics and physiological indicators. Thus, we set up two groups-a control group (DO 8.4 mg/L) and a hypoxic group (DO 0.39 mg/L)-to evaluate enzyme activity and the transcriptome, metabolome, and histomorphological characteristics. With blue-black chromatin, cell tightness, cell membrane invagination, and the production of apoptotic vesicles, tissue cells displayed typical apoptotic features in the hypoxic group. Although lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), catalase (CAT), and Na+/K+ -ATPase (NKA) activities were dramatically enhanced under hypoxic stress, glycogen content, and superoxide dismutase (SOD) activities were significantly reduced compared to the control group. The combined analysis of the transcriptome and metabolome, which further demonstrated, in addition to carbohydrates, including glycogen, the involvement of energy metabolism pathways, including fatty acid, protein, trehalose, and glyoxylate cycles, provided additional support for the aforementioned findings. Lactate is the end product of glycogen degradation, and HIF-1 plays an important role in promoting glycogenolysis in acute hypoxic conditions. However, we discovered that the ethanol tested under hypoxic stress likely originates from the symbiodinium of P. akamusi. These results imply that some parameters related to energy metabolism, antioxidant enzyme activities, and histomorphological features may be used as biomarkers of eutrophic lakes in Chironomus riparius larvae. The study also provides a scientific reference for assessing toxicity and favoring policies to reduce their impact on the environment.
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Osteosarcoma (OS) is the most frequent primary bone cancer, which is mainly suffered by children and young adults. While the current surgical treatment combined with chemotherapy is effective for the early stage of OS, advanced OS preferentially metastasizes to the lung and is difficult to treat. Here, we examined the efficacy of ten anti-OS peptide candidates from a trypsin-digested conditioned medium that was derived from the secretome of induced tumor-suppressing cells (iTSCs). Using OS cell lines, the antitumor capabilities of the peptide candidates were evaluated by assaying the alterations in metabolic activities, proliferation, motility, and invasion of OS cells. Among ten candidates, peptide P05 (ADDGRPFPQVIK), a fragment of aldolase A (ALDOA), presented the most potent OS-suppressing capabilities. Its efficacy was additive with standard-of-care chemotherapeutic agents such as cisplatin and doxorubicin, and it downregulated oncoproteins such as epidermal growth factor receptor (EGFR), Snail, and Src in OS cells. Interestingly, P05 did not present inhibitory effects on non-OS skeletal cells such as mesenchymal stem cells and osteoblast cells. Collectively, this study demonstrated that iTSC-derived secretomes may provide a source for identifying anticancer peptides, and P05 may warrant further evaluations for the treatment of OS.
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Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.
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BACKGROUND@#Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF.@*METHODS@#We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes.@*RESULTS@#A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system.@*CONCLUSIONS@#In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.
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OBJECTIVES@#Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.@*METHODS@#Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.@*RESULTS@#The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.@*CONCLUSION@#ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
Subject(s)
Animals , Mice , Cell Line, Tumor , Cell Movement , Cell Proliferation , China , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Invasiveness , Stomach Neoplasms/geneticsABSTRACT
Hongze Lake is the fourth largest freshwater lake in China and is an important source of water for surrounding industrial and agricultural processes and fishery resources. Analyzing the changes in the zooplankton community structure in Hongze Lake can provide scientific support for the scientific management of its ecology and environment. A one-year monthly monitoring study was conducted from March 2017 to February 2018 to analyze the temporal and spatial changes in species composition, density, and biomass of zooplankton in Hongze Lake, as well as the seasonal changes in community diversity and dominant species. Canonical correspondence analysis was employed to explore the relationships between the temporal and spatial changes in zooplankton and the environmental factors of Hongze Lake. The results showed that the average annual density of zooplankton in Hongze Lake was 383.87 ind ·L-1, and the average annual biomass was 1.36 mg ·L-1. The community structure of zooplankton in Hongze Lake varied greatly across time and space. Community structure varied greatly in summer, and zooplankton density and biomass reached a maximum in autumn. The community structure of the zooplankton was the simplest in winter. Chengzi Bay and Lihewa Bay exhibited an abundance of many different zooplankton species with limited spatial differentiation, whereas the zooplankton in the overflow area comprised fewer species but exhibited greater spatial variation. In summer, water level and temperature are the dominant factors, whereas in autumn and winter, the dominant factors are water temperature, nutrients, and chlorophyll. Canonical correspondence analysis showed that the temporal and spatial changes in zooplankton community structure in Hongze Lake were mainly determined by water level, total phosphorus, water temperature, and total nitrogen content. Water level fluctuation has the greatest direct impact on zooplankton community structure, and water quality regulation has indirect impact.
Subject(s)
Lakes , Zooplankton , Animals , China , Environmental Monitoring , Phytoplankton , SeasonsABSTRACT
Objective:To observe the interventative effect of Ziyin-Huatan Decoction by regulating exosomes on subcutaneous tumor of mice with gastric cancer. Methods:MGC-803 cells were randomly divided into exosome control group, low-dose group and high-dose group. The low-dose group and high-dose group were intervened with Ziyin-Huatan Decoction of 25 μg/ml and 100 μg/ml respectively. After 48 hours, the exosomes secreted by MGC-803 cells in each group were extracted. Twenty BALB/c male mice were randomly divided into exosome control group, low-dose Ziyin-Huatan Decoction group, high-dose Ziyin-Huatan Decoction group and blank control group, with 5 mice in each group. Except for the blank control group, the mice in the other groups were injected with exosomes extracted from the cells of the corresponding group through the orbit, 10 μg/time for each mouse, once every other day, a total of 15 times; the blank control group was injected with the same amount of PBS. Then SGC-7901 cells were inoculated into mice to establish a tumor model. The tumorigenic rate and body weight of mice were observed. The levels of CD31, VEGF and bFGF in tumor tissues were detected by immunohistochemistry. Results:Compared with the blank control group, the tumor weight [(170.00 ± 10.00) mg vs. (343.33 ± 20.82) mg] and the expression of CD31 (37.43 ± 0.55 vs. 63.30 ± 0.85), VEGF (11.37 ± 1.19 vs. 70.30 ± 0.72) and bFGF (43.77 ± 1.53 vs. 84.97 ± 1.86) in the high-dose Ziyin-Huatan Decoction group significantly decreased ( P<0.05). Compared with exosome control group, the expressions of CD31, VEGF and bFGF in low and high dose Ziyin-Huatan Decoction groups were decreased ( P<0.05). Conclusion:Ziyin-Huatan Decoction can significantly inhibit the growth of subcutaneous tumor of gastric cancer in mice by regulating exudation, which may be related to the inhibition of tumor angiogenesis.
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OBJECTIVE@#The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).@*METHODS@#Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.@*RESULTS@#Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.@*CONCLUSION@#Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.
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Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma/surgery , Esophagogastric Junction/surgery , Gastrectomy , Laparoscopy , Retrospective Studies , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
As a water storage lake for the South-to-North Water Diversion Project, it is crucial to examine changes in aquatic ecosystem structures in Lake Luoma, Jiangsu province. Field sampling was carried out in Lake Luoma monthly from 2014 to 2018 to study the relationship between the phytoplankton community structure and environmental factors. During the studied period, total nitrogen, permanganate index, and electrical conductivity in water column gradually increased, whereas fluoride content declined. The pattern of total phosphorus and dissolved oxygen was not distinct. A total of 71 genera of phytoplankton were identified from 2014 to 2018, and the average monthly biomass variation ranged from 0.16 to 5.51 mg·L-1. Bacillariophyta and Chlorophyta were the dominant phyla in the four years, followed by Pyrrophyta and Cryptophyta. The dominant genera were Synedra sp., Chroomonas spp., Aulacoseira spp., Dinobryon sp., Scenedesmus spp. , Fragilaria spp., Mougeotia sp. , Ankistrodesmus sp. , and Euglena spp. The results showed that the phytoplankton community structure significantly changed in the four years, which was mainly ascribed to the redistribution of biomass. Specifically, in addition to the dominance of Bacillariophyta and Chlorophyta, the dominance of Pyrrophyta and Cyanophyta increased during the last two years. Non-metric multidimensional scaling analysis showed that variation of the phytoplankton community in Lake Luoma was mainly related to total nitrogen, fluoride, water temperature, total phosphorus, dissolved oxygen, pH, conductivity, and permanganate index, among which the total nitrogen, water temperature, and fluoride concentration dominated the phytoplankton community change after the generalized additive model test. Water temperature is the driving factor affecting seasonal changes of the phytoplankton community. Total nitrogen and fluoride concentrations are the driving factors affecting the interannual variation in the phytoplankton community. Our study indicated that in recent years, the implementation of the ban on sand mining and demolition of the enclosed aquaculture in Lake Luoma has affected the water environment, resulting in a significant succession of the phytoplankton community.
Subject(s)
Lakes , Phytoplankton , China , Ecosystem , Environmental Monitoring , Nitrogen/analysis , Phosphorus/analysis , SeasonsABSTRACT
Agenesis of the dorsal pancreas is a rare congenital pancreatic malformation. We herein describe a 67-year-old woman with a 5-day history of lower back pain who was eventually diagnosed with agenesis of the dorsal pancreas. Abdominal computed tomography showed an enlarged pancreatic head, but the pancreatic body and tail were invisible. The magnetic resonance imaging findings were similar to the computed tomography findings. Magnetic resonance cholangiopancreatography showed that the major pancreatic duct was mildly dilated but otherwise normal. Endoscopic ultrasound revealed absence of the pancreatic body and tail, an enlarged head of the pancreas, and mild pancreatic duct dilation. The final diagnosis was dorsal pancreatic agenesis.
Subject(s)
Congenital Abnormalities/diagnostic imaging , Endosonography , Low Back Pain/etiology , Pancreas/abnormalities , Aged , Alprostadil/administration & dosage , Cholangiopancreatography, Magnetic Resonance , Enzyme Replacement Therapy , Female , Humans , Low Back Pain/drug therapy , Pancreas/diagnostic imaging , Pantoprazole/administration & dosage , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE@#To study the association of the polymorphisms of the serum amyloid A1 (SAA1) gene at rs4638289 and rs7131332 loci with Kawasaki disease (KD) and its complication coronary artery lesion (CAL) in children.@*METHODS@#A total of 105 Han children with KD who were hospitalized and treated from 2013 to 2017 were enrolled as the KD group. A total of 100 Han children who underwent physical examination were enrolled as the control group. According to the presence or absence of CAL, the KD group was further divided into a CAL group with 23 children and a non-CAL (NCAL) group with 82 children. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the polymorphisms of the SAA1 gene at rs4638289 and rs7131332 loci.@*RESUKTS@#For the locus rs4638289 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AT, and TT and the allele frequencies of A and T (P>0.05). But there were significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AT, and TT (P=0.016), while there were no significant differences in the allele frequencies of A and T (P>0.05). AT genotype was a protective factor against CAL (OR=0.276, 95%CI: 0.099-0.772, P=0.011). For the locus rs7131332 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). There were also no significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05).@*CONCLUSIONS@#Polymorphisms of the SAA1 gene at loci rs4638289 and rs7131332 are not associated with the onset of KD, while the polymorphism at the locus rs4638289 is associated with CAL in KD patients. KD patients with genotype AT may have a reduced risk of CAL.
Subject(s)
Child , Humans , Case-Control Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Mucocutaneous Lymph Node Syndrome , Genetics , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Serum Amyloid A Protein , GeneticsABSTRACT
ObjectiveTo observe the role of parvalbumin interneuron-mediated disinhibition in the antidepressant effects of ketamine.MethodsForty-eight adult male C57BL/6 mice were randomly divided into the following four groups (n=12): group Saline + Saline (group SS), group LPS + Saline (group LS), group Saline + Ketamine (group SK) and group LPS + Ketamine (group LK). The depression model was established by intraperitoneal injection of LPS (1 mg/kg), and ketamine (10 mg/kg) or physiological saline (equal volume) intraperitoneally injected 20 hours later. Four hours after ketamine administration, the open field test and the forced swimming test were performed. The hippocampus was harvested after the behavioral test. PCR and Western blot were used to detect the expressions of PV and GAD67. Electrophysiology were used to detect the change of miniExcitatory post-synaptic current of pyramidal neurons in hippocampus CA1 region.ResultsCompared with the group SS, the time spent in the center zone of the arena was significantly decreased, the immobility time was significantly increased, the mRNA and protein content of PV were significantly increased, the amplitude and frequency of miniEPSC were significantly decreased in the group LS (P0.05).ConclusionKetamine can exert rapid antidepressant effects by down-regulating the expression of PV and then exerting disinhibition regulation on pyramidal neurons.
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The MYB transcription factor (TF) superfamily, one of the largest gene superfamilies, regulates a variety of physiological processes in plants. Although many MYB superfamily genes have been identified in plants, the MYB TFs in Chinese jujube (Ziziphus jujuba Mill.) have not been fully identified and characterized. Additionally, the functions of these genes remain unclear. In total, we identified 171 MYB superfamily genes in jujube and divided them into five subfamilies containing 99 genes of the R2R3-MYB subfamily, 58 genes of the MYB-related subfamily, four genes of the R1R2R3-MYB subfamily, one gene of the 4R-MYB subfamily, and nine genes of the atypical MYB subfamily. The 99 R2R3-MYB genes of jujube were divided into 35 groups, C1-C35, and the 58 MYB-related genes were divided into the following groups: the R-R-type, CCA1-like, I-box-binding-like, TBP-like, CPC-like, and Chinese jujube-specific groups. ZjMYB genes in jujube were well supported by additional highly conserved motifs and exon/intron structures. Most R1 repeats of MYB-related proteins comprised the R2 repeat and had highly conserved EED and EEE residue groups in jujube. Three tandem duplicated gene pairs were found on 12 chromosomes in jujube. According to an expression analysis of 126 ZjMYB genes, MYB-related genes played important roles in jujube development and fruit-related biological processes. The total flavonoid content of jujube fruit decreased as ripening progressed. A total of 93 expressed genes were identified in the RNA-sequencing data from jujube fruit, and 56 ZjMYB members presented significant correlations with total flavonoid contents by correlation analysis. Five pairs of paralogous MYB genes within jujube were composed of nine jujube MYB genes. A total of 14 ZjMYB genes had the same homology to the MYB genes of Arabidopsis and peach, indicating that these 14 MYB genes and their orthologs probably existed before the ancestral divergence of the MYB superfamily. We used a synteny analysis of MYB genes between jujube and Arabidopsis to predict that the functions of the ZjMYBs involve flavonoid/phenylpropanoid metabolism, the light signaling pathway, auxin signal transduction, and responses to various abiotic stresses (cold, drought, and salt stresses). Additionally, we speculate that ZjMYB108 is an important TF involved in the flavonoid metabolic pathway. This comprehensive analysis of MYB superfamily genes in jujube lay a solid foundation for future comprehensive analyses of ZjMYB gene functions.
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Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed significantly increased proliferation and differentiation. We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products, i.e., IL-1 family members such as IL-1ß and IL-18 were upregulated in the PVAT of obese mini pigs; PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid. Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.
Subject(s)
Adipose Tissue/physiopathology , Adventitia/physiopathology , Blood Vessels/physiopathology , Obesity/physiopathology , Vascular Remodeling/physiology , Animals , Cell Differentiation/physiology , Cell Proliferation/physiology , Fibroblasts/physiology , Inflammasomes/metabolism , Interleukin-1/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction , Swine , Swine, MiniatureABSTRACT
Objective@#To investigate the changes in ventricular late potentials (VLP) in children and adolescents with postural tachycardia syndrome (POTS).@*Methods@#One hundred and forty-four children and adolescents diagnosed as POTS by using the head-up tilt test (HUTT) in Second Xiangya Hospital of Central South University from January 2012 to March 2019 were selected as POTS group, their age ranged 4 to 16 years old[(11.03±2.34)years old], there were 65 boys and 79 girls.Ninety-one healthy children and adolescents matched by age and gender[aged 4-16 (11.22±1.68) years old, there were 50 boys and 41 girls]were selected as the healthy control group.VLP was measured by SR-1000A ECG automatic analyzer (Boai, Guangdong, China).@*Results@#Compared with the healthy control group, the prevalence of positive VLP in the POTS group increased [ 11.1%(16/144 cases)vs.1.1%(1/91cases)], and the difference was statistically significant(χ2= 6.904, P<0.01); the heart rate in the POTS group increased compared with that in the healthy control group[82.0 (74.0-95.0) times/min vs.78.0 (71.0-86.0) times/min], and the difference was statistically significant(Z=-2.265, P<0.05); the low-amplitude signal(LAS40) in the POTS group prolonged compared with that in the healthy control group[23.0 (17.0-31.0) μV vs.19.0 (13.0-25.0) μV], and the difference was statistically significant(Z=-4.114, P<0.01); root mean square amplitude(RMS40) increased compared with that in the healthy control group[61.3 (34.4-79.1) ms vs.52.0 (38.8-64.5) ms], and the difference was statistically significant (Z=-2.469, P<0.05). There was no statistically significant difference in total QRS time (TQRS) between 2 groups [86.0 (76.0-97.5) ms vs.87.0 (81.0-94.0) ms, Z=-0.007, P>0.05].@*Conclusions@#The positive rate of VLP is increased of children and adolescents with POTS.It suggests that there is an abnormal cardiac electrical activity in children and adolescents with POTS.
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OBJECTIVE@#To study the change in P wave on electrocardiogram and its diagnostic value in children and adolescents with cardioinhibitory vasovagal syncope (VVS-CI).@*METHODS@#A total of 43 children and adolescents who were diagnosed with VVS-CI were enrolled as the VVS-CI group, and 43 healthy children and adolescents were enrolled as the control group. P wave duration and P wave voltage were measured by 12-lead electrocardiography in a basal state, and the changes were analyzed.@*RESULTS@#Compared with the control group, the VVS-CI group had a significantly lower heart rate (P<0.05) and significantly longer P wave duration (Pwd), P wave maximum duration (Pmax), and corrected P wave maximum duration (Pcmax), as well as significantly higher P wave dispersion (Pd) and corrected P wave dispersion (Pcd) (P<0.05). Pwd, Pmax, Pd, Pcmax and Pcd had a certain diagnostic value in children and adolescents with VVS-CI (P<0.05): Pwd had a sensitivity of 69.77% and a specificity of 83.72% at the optimal cut-off value of 78.49 ms; Pmax had a sensitivity of 76.74% and a specificity of 90.70% at the optimal cut-off value of 93.39 ms; Pd had a sensitivity of 95.35% and a specificity of 69.77% at the optimal cut-off value of 27.42 ms; Pcmax had a sensitivity of 46.51% and a specificity of 88.37% at the optimal cut-off value of 120.90 ms; Pcd had a sensitivity of 83.72% and a specificity of 72.09% at the optimal cut-off value of 36.37 ms.@*CONCLUSIONS@#Children and adolescents with VVS-CI have significantly increased Pwd, Pmax, Pd, Pcmax, and Pcd, which may indicate abnormal atrial electrical activity. The cut-off value of P wave has a certain diagnostic value in VVS-CI.
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Adolescent , Child , Humans , Electrocardiography , Heart Rate , Syncope, VasovagalABSTRACT
Objective To investigate the changes in ventricular late potentials (VLP) in children and adolescents with postural tachycardia syndrome (POTS).Methods One hundred and forty-four children and adolescents diagnosed as POTS by using the head-up tilt test (HUTT) in Second Xiangya Hospital of Central South University from January 2012 to March 2019 were selected as POTS group,their age ranged 4 to 16 years old [(11.03 ± 2.34) years old],there were 65 boys and 79 girls.Ninety-one healthy children and adolescents matched by age and gender [aged 4-16 (11.22 ± 1.68) years old,there were 50 boys and 41 girls] were selected as the healthy control group.VLP was measured by SR-1000A ECG automatic analyzer (Boai,Guangdong,China).Results Compared with the healthy control group,the prevalence of positive VLP in the POTS group increased [11.1％ (16/144 cases)vs.1.1％ (1/91 cases)],and the difference was statistically significant(x2=6.904,P ＜ 0.01);the heart rate in the POTS group increased compared with that in the healthy control group [82.0 (74.0-95.0) times/min vs.78.0 (71.0-86.0) times/min],and the difference was statistically significant (Z =-2.265,P ＜ 0.05);the low-amplitude signal (LAS40) in the POTS group prolonged compared with that in the healthy control group[23.0 (17.0-31.0) μV vs.19.0 (13.0-25.0) μV],and the difference was statistically significant (Z =-4.114,P ＜ 0.01);root mean square amplitude(RMS40) increased compared with that in the healthy control group [61.3 (34.4-79.1) ms vs.52.0 (38.8-64.5) ms],and the difference was statistically significant (Z =-2.469,P ＜ 0.05).There was no statistically significant difference in total QRS time (TQRS) between 2 groups [86.0 (76.0-97.5) ms vs.87.0 (81.0-94.0) ms,Z =-0.007,P ＞ 0.05].Conclusions The positive rate of VLP is increased of children and adolescents with POTS.It suggests that there is an abnormal cardiac electrical activity in children and adolescents with POTS.
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OBJECTIVE@#To screen the antioxidant small molecular compounds with optimal efficiency of expansing the human hematopoietic stem cells (hHSC) In vitro based on antioxidant small molecular compound database of LKT laboratory, and to verify the effects of these compounds on the biological functions of hHSC.@*METHODS@#The umbilial cord blood CD34 cells were enriched by using the MACS beads; the absolute number and percentage of CD34 cells and CD34 CD49f cells were detected by high throughput flow cytometry after culture of hHSC with compounds in vitro for 1 week, the SR1 (1 μmol/L) was used as positive control, the candidate compounds were screened out; then 4 compounds were selected for follow-up experiments by comprehensive evaluation of concentration, safety and expansion efficacy, the optimal used concentrations of selected compounds were determined through the concentration gradient analysis, and CFC short-term colony-forming cell test was performed by using the determined concentration so as to verify the effect of compounds on the self-renewal, multilineage differentiation.@*RESULTS@#Out of 85 antioxidant small molecular compounds, 4 compounds (C2968, D3331, B1753 and B3358) with obvious expansion efficacy for CD34 cells and CD34 CD49f cells were screened out by high throughput flow cytometry; their optimal concentrations of 4 compounds were 0.5 μmol/L for C2968, 1.5 μmol/L for D3331 and 1.5 μmol/L for B1753 and 15 μmol/L for B3358. The CFC assay showed the colony formation number in compound-treated group significantly increased as compared with control group, moreover the self-renewal and multilineage differentiation were maintained.@*CONCLUSION@#The antioxidant small molecular compounds C2968 (0.5 μmol/L), D3331 (1.5 μmol/L), B1753 (1.5 μmol/L) and B3358 (1.5 μmol/L) possess good expansion efficacy for hHSC, they can maintain hHSC self-renewal, at the same time ensure the multilineage differentiation potentiality of hHSC.
