ABSTRACT
Histone deacetylases (HDACs), known as histone acetylation erasers, function crucially in plant growth and development. Although there are abundant reports focusing on HDACs of Arabidopsis and illustrating their important roles, the knowledge of HDAC genes in Tartary buckwheat (Polygonales Polygonaceae Fagopyrum tataricum (L.) Gaertn) is still scarce. In the study, a total of 14 HDAC genes were identified and divided into three main groups: Reduced Potassium Dependency-3/His-52 tone Deacetylase 1 (RPD3/HDA1), Silent Information Regulator 2 (SIR2), and the plant-53 specific HD2. Domain and motif composition analysis showed there were conserved domains and motifs in members from the same subfamilies. The 14 FtHDACs were distributed asymmetrically on 7 chromosomes, with three segmental events and one tandem duplication event identified. The prediction of the cis-element in promoters suggested that FtHDACs probably acted in numerous biological processes including plant growth, development, and response to environmental signals. Furthermore, expression analysis based on RNA-seq data displayed that all FtHDAC genes were universally and distinctly expressed in diverse tissues and fruit development stages. In addition, we found divergent alterations in FtHDACs transcript abundance in response to different light conditions according to RNA-seq and RT-qPCR data, indicating that five FtHDACs might be involved in light response. Our findings could provide fundamental information for the HDAC gene family and supply several targets for future function analysis of FtHDACs related with light response of Tartary buckwheat.
Subject(s)
Fagopyrum , Fagopyrum/metabolism , Phylogeny , Histone Deacetylases/metabolism , Gene Expression Profiling , Genome, Plant , Plant Proteins/metabolism , Gene Expression Regulation, PlantABSTRACT
This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.
Subject(s)
COVID-19 Vaccines , COVID-19 , Child , Animals , Humans , Macaca mulatta , Spike Glycoprotein, Coronavirus , COVID-19/prevention & control , SARS-CoV-2 , BibliometricsABSTRACT
This study investigated the mechanisms of Jingfang Granule (JFG) in viral myocarditis (VMC) treatment via network pharmacology-based approach combined with molecular docking and validated the results through in vitro and in vivo experiments. The chemical composition of JFG and its therapeutic targets was queried in Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets related to VMC were retrieved from the disease database, and the overlapping targets were screened. Based on the STRING database, a protein-protein interaction network was constructed. Cytoscape software was used to construct the "component-target-disease" interaction network for visualization. GO and KEGG pathway enrichment analyses were performed using Metascape data. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software programs. The target genes were further verified in vitro and in vivo. JFG contains 88 active components. The main biological targets of JFG in VMC include quercetin, luteolin, and kaempferol. The molecular docking results showed that the three key targets showed strong binding properties with both the height components of the molecular docking interaction energies. The results of experimental verification results showed that JFG may be used to treat VMC mainly by down-regulating inflammatory factors TNF-α and NF-κB and inhibiting myocardial apoptosis. The results support the network pharmacological data. JFG reduces myocardial inflammation and myocardial cell apoptosis in VMC and protects myocardial tissue.
Subject(s)
Myocarditis , Humans , Myocarditis/drug therapy , Network Pharmacology , Molecular Docking Simulation , Myocardium , ApoptosisABSTRACT
Background: Venous thromboembolism is a common complication in patients with colorectal cancer who exhibit high homocysteine and low folate levels. However, whether venous thrombosis is the result of a direct effect of folic acid or the presence of a homocysteine-mediated mediating effect cannot be determined. This study aimed to explore the association and mediating effects of serum folate and homocysteine on venous thromboembolism in patients with colorectal cancer. Methods: This study included patients with colorectal cancer who were admitted to the First Hospital of Shanxi Medical University from May 2020 to May 2022. The patients' medical records were reviewed to collect information on general demographic characteristics, the prevalence of venous thromboembolism on admission, laboratory blood indices, serum folate, and serum homocysteine. SPSS 26.0 software was used for data collation and statistical analysis; the χ2 test was utilized for univariate analysis and unconditional logistic regression was applied for multivariate analysis. R 4.1.2 was used to perform the mediating effect test. Results: A total of 236 colorectal cancer patients were investigated. The prevalence of colorectal cancer combined with venous thromboembolism was 15.3%; serum folate was <10.75 nmol/L in 25.4% of patients; and serum homocysteine was ≥22 µmol/L in 30.5% of patients. After controlling for confounding factors, the risk of venous thromboembolism was 2.48 times greater [95% confidence interval (CI): 1.04 to 5.94] in patients with low serum folate (<10.75 nmol/L) than in those with high serum folate (≥10.75 nmol/L). Also, the risk of venous thromboembolism was greater in those with high serum homocysteine (≥22 µmol/L) [odds ratio (OR) =2.99. 95% CI: 1.11 to 8.08]. The mediating effect test showed no direct effect of serum folate on venous thromboembolism combined with colorectal cancer, and a full mediating effect of serum homocysteine between serum folate and venous thromboembolism combined with colorectal cancer, with a mediating effect value of 0.002 and a total effect value of 0.0054. Conclusions: Serum folate influences the formation of venous thromboembolism through serum homocysteine. It is recommended that the nutritional supplementation of patients be enhanced to control serum folate and serum homocysteine levels.
ABSTRACT
Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , Female , Humans , Infant , Infant, Newborn , Pregnancy , Dietary Supplements , Hepatitis B/prevention & control , Hepatitis B/drug therapy , Hepatitis B Antibodies , Hepatitis B Vaccines/therapeutic use , Interleukin-4 , Pregnant Women , Folic Acid/pharmacologyABSTRACT
Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor playing crucial roles in various biological process in plant. However, thorough research on NF-Y gene family of Tartary buckwheat (Fagopyrum tataricum) is little. In this study, 38 FtNF-Y genes (12 FtNF-YAs, 17 FtNF-YBs, and 9 FtNF-YCs) were identified and renamed on the basis of their subfamily and chromosomal location. Their gene structure, genomic mapping, motif composition, conserved domain, phylogenetic relationships, cis-acting elements and gene expression were investigated. Illustration of gene structures and conserved domains of FtNF-Ys revealed their functional conservation and specificity. Construction of phylogenetic trees of NF-Ys in Tartary buckwheat, Arabidopsis, tomato, rice and banana, allowed us to predict functional similarities among NF-Ys from different species. Gene expression analysis displayed that twenty-four FtNF-Ys were expressed in all the tissues and the transcript levels of them were different, suggesting their function varieties. Moreover, expression profiles of twenty FtNF-Ys along five different fruit development stages acquired by real-time quantitative PCR (RT-qPCR) demonstrated distinct abundance diversity at different stages, providing some clues of potential fruit development regulators. Our study could provide helpful reference information for further function characterization of FtNF-Ys and for the fruit quality enhancement of Tartary buckwheat.
Subject(s)
CCAAT-Binding Factor/genetics , Fagopyrum/genetics , Fruit/growth & development , Fruit/genetics , Genome, Plant , Multigene Family , Plant Proteins/genetics , Amino Acid Motifs , Amino Acid Sequence , CCAAT-Binding Factor/chemistry , Chromosomes, Plant/genetics , Conserved Sequence , Evolution, Molecular , Gene Duplication/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant , Organ Specificity/genetics , Phylogeny , Plant Proteins/chemistry , Promoter Regions, Genetic/geneticsABSTRACT
BACKGROUND: To investigate the incidence of anxiety and depressive disorders in young adults with obesity and the correlation between the severity of these disorders and hypothalamic inflammation. METHODS: The severity of anxiety and depressive disorders was assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), respectively. Hypothalamic inflammation was evaluated by measuring the hypothalamus/amygdala (H/A) signal intensity (SI) ratio in T2-weighted phase quantitative magnetic resonance imaging (MRI). RESULTS: The incidence of depressive disorders in young (18-45 years) patients with obesity (n=66) was higher than that in the control group (n=44); anxiety disorder incidence did not differ significantly between groups. The bilateral H/A SI ratio in the obesity group was significantly higher than that in the control group. In the obesity group, there was no significant correlation between bilateral H/A SI ratio and body mass index (BMI) (right: r=-0.145, P=0.721; left: r=0.102, P=0.415) or SAS scores (right: r=-0.118, P=0.444; left: r=-0.295, P=0.052); SDS scores were significantly correlated with left H/A SI ratio (r=-0.353, P=0.019), but not right H/A SI ratio (r=-0.031, P=0.843). CONCLUSIONS: Patients with obesity had a higher incidence of depressive disorders. Left hypothalamus inflammation may be one of the links between obesity and depressive disorders.
Subject(s)
Anxiety , Depression , Anxiety Disorders , Humans , Hypothalamus , Inflammation/diagnostic imaging , Obesity , Young AdultABSTRACT
Objective: To observe the efficacy of long-retaining scalp acupuncture plus interactive training in improving upper- extremity dysfunction in cerebral stroke patients. Methods: Ninety-five patients with upper-extremity dysfunction after cerebral stroke were randomized into two groups, with 48 cases in the treatment group and 47 cases in the control group. Conventional internal medicine treatment was offered to both groups. In both groups, Anterior Oblique Line of Vertex-temporal (MS 6, the middle 2/5) and Posterior Oblique Line of Vertex-temporal (MS 7, the middle 2/5) were selected from the same side of the brain lesion (the side apposing to the hemiplegic limb) for scalp acupuncture treatment. In the treatment group, the scalp acupuncture needles were retained for 7 h, in combination with interactive training, while the needles were also retained for 7 h in the control group but without interactive training. Prior to treatment and at 2-week and 4-week treatment, the two groups were scored using the functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK) and simplified Fugl-Meyer assessment-upper extremity (FMA-UE). Results: The total effective rate was 97.9% in the treatment group, higher than 74.5% in the control group (P<0.01). The FTHUE-HK score was higher at 2-week and 4-week treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FTHUE-HK score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FTHUE-HK score was higher in the treatment group than in the control group, showing significant between-group differences (both P<0.05). During the whole treatment process, the treatment group had higher FTHUE-HK scores compared with the control group, but there was no statistical significance comparing the change of the score between the two groups at 2-week treatment (P>0.05), while the between-group difference in the change of the score was statistically significant at 4-week treatment (P<0.05). The FMA-UE score was higher at 2-week and 4-weeks treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FMA-UE score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FMA-UE was higher in the treatment group than in the control group, and the between-group differences were statistically significant (both P<0.01). The FMA-UE score rose gradually with the increase of treatment session, and there was statistical significance comparing the change of the score between the two groups at 2-week and 4-week treatment, respectively (both P<0.05). Conclusion: Long-retaining scalp acupuncture plus interactive training results in more significant efficacy than long-retaining scalp acupuncture alone in improving the upper-limb dysfunction after cerebral stroke and the advantage becomes more notable after 2-week consecutive treatment.
ABSTRACT
We report here an ultrasensitive strategy based on the recognition-induced conformational alteration of aptamer and fluorescence turn-on abilities of guanine-rich (G-rich) DNA sequence in proximity to silver nanoclusters for adenosine triphosphate (ATP), adenosine (A) and thrombin (TB) detection. Herein, we designed two tailored DNA sequences noted as complementary DNA (abbreviated as c-DNA) and signal probe DNA (abbreviated as s-DNA), respectively. c-DNA is designed as a special structure consisting of a sequence complementary to aptamer at the 3'-end and a guanine-rich DNA sequence at the 5'-end; s-DNA contains a cytosine-rich sequence responsible for Ag NCs templated synthesis at the 3'-end and a link sequence (part of aptamer) complementary to partial of the c-DNA at the 5'-end. In the presence of target, the aptamer associated with the target, resulting in the formation of duplex DNA (dsDNA), the DNA-Ag NCs thereafter could close to the guanine-rich sequence, leading to enhanced fluorescence signal readout. The widespread application of the sensing system is achieved success in the detection of three biomolecules. ATP, adenosine and thrombin in the range of 0.5-8.0 µM, 0.5-7.0 µM and 50-900 nM could be linearly detected with the detection limits of 91.6 nM, 103.4 nM and 8.4 nM, respectively. This label-free and turn-on fluorescent sensing system employing the mechanism proposed here turns out to be sensitive, selective, and convenient for the detection of biomolecules without washing and separation steps.
Subject(s)
Adenosine Triphosphate/isolation & purification , Adenosine/isolation & purification , Biosensing Techniques , Thrombin/isolation & purification , Aptamers, Nucleotide/chemistry , Fluorescence , Light , Metal Nanoparticles/chemistry , Silver/chemistryABSTRACT
BACKGROUND: The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. METHODS: Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. RESULTS: GXST significantly decreased levels of TNF-α, IL-1ß, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). CONCLUSIONS: GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.
ABSTRACT
OBJECTIVE: To assess the effects of Guanxinshutong capsule (GXST) on protection of left ventricular (LV) function after acute myocardial infarction (AMI) in rats. METHODS: Twenty-eight male Sprague Dawley rats were randomized to Model group, Drug group and Sham-operated group, with acute myocardial infarction (AMI) achieved by ligating coronary artery in Model and Drug groups. From one week before surgery to four weeks after surgery, GXST for Drug group (1.5 g/kg, 2 times/day) or saline for Model and Sham-operated groups was administered via direct gastric gavage. After four weeks of treatment following surgery, measurement of LV function, pathohistological observation and analysis were performed. RESULTS: Compared with rats in the Model group, LV systolic pressure (LVSP) [(97.7 ± 9.0) mm Hg (1 mm Hg = 0.133 kPa) vs (85.9 ± 9.4) mm Hg], the maximum rising rate of LV pressure (+dp/dtmax) [(4810.2 ± 595.0) mm Hg/s vs (3786.2 ± 723.0) mm Hg/s] and the maximum dropping rate of LV pressure (-dp/dtmax) [(3781.6 ± 573.6) mm Hg/s vs (2774.4 ± 633.5)mm Hg/s] in the Drug group were significantly increased, while LV end-diastolic pressure (LVEDP) [(10.3 ± 0.7) mm Hg vs (12.7 ± 2.4) mm Hg] in the Drug group was significantly decreased (all P < 0.05). Myocardial pathohistological morphology was improved in the Drug group with fibrosis alleviated [(5.13 ± 1.37)% vs (7.27 ± 1.01)%] and infarct size reduced [(20.14 ± 8.49)% vs (31.90 ± 4.98)%]. Apoptosis index (AI) was decreased [(14.05 ± 4.04)% vs (20.87 ± 6.03)%] and vessel density was significantly increased by 1.48-fold in the Drug group (all P < 0.05). CONCLUSIONS: GXST is effective in protecting LV function after AMI in rats, which may be affect through increasing vessel density of infarction area, improving myocardial pathohistological morphology, alleviating fibrosis, reducing infarct size and decreasing AI.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Ventricular Function, Left/drug effects , Animals , Drugs, Chinese Herbal/therapeutic use , Male , Myocardial Infarction/drug therapy , Phytotherapy , Rats , Rats, Sprague-Dawley , Ventricular RemodelingABSTRACT
Drug-resistant (including multidrug-resistant) bacteria increase continuously with the wide use of antibiotics, which have seriously threatened the human health. It is an important way to fight against drug-resistance by screening and developing novel drugs based on the various mechanisms of the bacterial drug tolerances. Meanwhile, the basic research related to the new drug R. & D. and studies on the new screening methods for the antimicrobial agents should be taken seriously and strengthened, so as to accelerate the process of finding new drugs and meet the challenge of new pathogens and new drug-resistant strains.
Subject(s)
Anti-Bacterial Agents , Bacteria/drug effects , Drug Design , Drug Resistance, Multiple, Bacterial , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Bacterial Physiological Phenomena/drug effects , Drug Evaluation, Preclinical , Drug Resistance, Multiple, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/physiology , Humans , PeptidesABSTRACT
OBJECTIVE: To establish an efflux pump inhibitor screening model with the out-membrane protein OprM in Pseudomonas aeruginosa efflux pump system as the target point. METHODS: Efflux pump out-membrane protein gene oprM was obtained from standard Pseudomonas aeruginosa PA01 strain. Expression of OprM protein was induced in E. coli strain HS151 with T-easy vector as the cloning vector, and pMMB67EH as the expression vector. In order to evaluate the function of OprM protein, we measured intracellular tetracycline concentrations with liquid scintillation counter, measured the diameters of bacteriostatic circles with paper disc, and then established a screening model accordingly. RESULTS: OprM protein was highly expressed. Using Pseudomonas aeruginosa as the main detecting bacteria, we established a drug screening model acting on OprM. A total of 1 600 microbial fermentation samples were screened with this model, among which 56 positive strains were found, with a positive rate of 3.5%. CONCLUSION: OprM plays an important role in drug efflux. The established model has good specificity and maneuverability.