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1.
Plant Physiol Biochem ; 212: 108783, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38824694

ABSTRACT

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 µmol m-2·s-1; T2, 3R: 1B, 279.69 µmol m-2·s-1; T3, 7R: 1B, 211.16 µmol m-2·s-1). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment.

2.
Ultrason Sonochem ; 104: 106815, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38484470

ABSTRACT

Abelmoschus manihot (L) is a traditional chinese herb and the present study focused on its comprehensive development and utilization. Enzyme-assisted ultrasonic extraction (EUAE) was investigated for the extraction and qualitative and quantitative analysis of flavonoids from Abelmoschus manihot (L) using a combination of ultra-performance liquid chromatography-photodiode array (UPLC-PDA), polysaccharides was extracted from residues and compared with directly extracted from raw materials. The optimal yield of 3.46±0.012 % (w/w) was obtained when the weight ratio of cellulase to pectinase was 1:1, the enzyme concentration was 3 %, the pH was 6.0, the solvent was a mixture of 70 % ethanol (v/v) and 0.1 mol/L NaH2PO4 buffer solution, the ultrasonic power was 500 W, the extraction time was 40 min, and the temperature of the extraction was 50 °C. The individual concentrations of interested flavonoids (rutin, neochlorogenic acid, nochlorogenic acid, lsoquercitrin, quercitrin, gossypin, quercetin) were effectively increased with the using of EUAE, compared with ultrasonic extraction (UE) method. Polysaccharides were extracted from each residue, respectively, the Polysaccharides yield in residue from EUAE was higher than that from UE, and closed to the yield from direct extraction in raw materials. The above results shown that the experimental process had the potential to be environmentall, friendly, straightforward and efficient.


Subject(s)
Abelmoschus , Ultrasonics , Abelmoschus/chemistry , Plant Extracts/chemistry , Flavonoids/analysis , Polysaccharides/chemistry
3.
Curr Issues Mol Biol ; 45(9): 7304-7318, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37754246

ABSTRACT

An essential indicator of Eucommia ulmoides Oliver (E. ulmoides) is the axillary bud; the growth and developmental capacity of axillary buds could be used to efficiently determine the structural integrity of branches and plant regeneration. We obtained axillary buds in different positions on the stem, including upper buds (CK), tip buds (T1), and bottom buds (T2), which provided optimal materials for the study of complicated regulatory networks that control bud germination. This study used transcriptomes to analyze the levels of gene expression in three different types of buds, and the results showed that 12,131 differentially expressed genes (DEGs) were discovered via the pairwise comparison of transcriptome data gathered from CK to T2, while the majority of DEGs (44.38%) were mainly found between CK and T1. These DEGs were closely related to plant hormone signal transduction and the amino acid biosynthesis pathway. We also determined changes in endogenous hormone contents during the process of bud germination. Interestingly, except for indole-3-acetic acid (IAA) content, which showed a significant upward trend (p < 0.05) in tip buds on day 4 compared with day 0, the other hormones showed no significant change during the process of germination. Then, the expression patterns of genes involved in IAA biosynthesis and signaling were examined through transcriptome analysis. Furthermore, the expression levels of genes related to IAA biosynthesis and signal transduction were upregulated in tip buds. Particularly, the expression of the IAA degradation gene Gretchen Hagen 3 (GH3.1) was downregulated on day 4, which may support the concept that endogenous IAA promotes bud germination. Based on these data, we propose that IAA synthesis and signal transduction lead to morphological changes in tip buds during the germination process. On this basis, suggestions to improve the efficiency of the production and application of E. ulmoides are put forward to provide guidance for future research.

4.
Acta Biomater ; 155: 601-617, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36400350

ABSTRACT

Despite the great promise initially demonstrated by photothermal ablation (PTA) therapy, its inability to completely ablate large tumors is problematic, because this has been found to result in residual tumors at ablation margins and bring a relative high rate of subsequent recurrences and metastases. To address this issue, we herein report a smart photothermal nanosystem (PBM) based on FDA-approved Prussian blue (PB) nanoparticles, doped with Mn (III) to suppress the tumor debris left by incomplete ablation. Notably, our study demonstrated that PTA-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway by generating damaged cytosolic DNA. This PBM nanosystem, which consumes glutathione and continuously releases Mn(II), further amplifies the PTA-induced cGAS-STING pathway in CT26 colon and 4T1 breast tumor models. Moreover, treatment with PBM following PTA boosted the robust immune response in situ and extended to the whole body with a remarkable suppression effect on both local residual and distant tumors. This work, which improves the antitumor efficacy of nonablated areas utilizing hyperthermia-enhanced immune therapy, may therefore provide a promising adjuvant antitumor strategy for the issue of incomplete ablation. STATEMENT OF SIGNIFICANCE: This work discovered, for the first time, that photothermal ablation-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway. Taking advantage of this finding, we developed a smart photothermal material (PBM) tailored for incomplete tumor ablation. This integrated Mn(III)-doped nanosystem (PBM) demonstrated superior therapeutic benefits due to the thermal ablation process and immune enhancement. As the photothermal ablation-induced cGAS-STING pathway was triggered, the released Mn(III) consumes GSH while continuously transferred to Mn(II), which further amplified STING activation and facilitated a more robust antitumor immunity, thereby remarkably inhibiting both local residual and distant tumors in virtue of the biological changes under thermal ablation.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Humans , Manganese/pharmacology , Neoplasms/therapy , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism
5.
Molecules ; 27(9)2022 Apr 28.
Article in English | MEDLINE | ID: mdl-35566163

ABSTRACT

The emergence of the plasmid-mediated colistin resistance gene mcr-1 has resulted in the loss of available treatments for certain severe infections. Here we identified a potential inhibitor of MCR-1 for the treatment of infections caused by MCR-1-positive drug-resistant bacteria, especially MCR-1-positive carbapenem-resistant Enterobacteriaceae (CRE). A checkerboard minimum inhibitory concentration (MIC) test, a killing curve test, a growth curve test, bacterial live/dead assays, scanning electron microscope (SEM) analysis, cytotoxicity tests, molecular dynamics simulation analysis, and animal studies were used to confirm the in vivo/in vitro synergistic effects of pogostone and colistin. The results showed that pogostone could restore the bactericidal activity of colistin against all tested MCR-1-positive bacterial strains or MCR-1 mutant−positive bacterial strains (FIC < 0.5). Pogostone does not inhibit the expression of MCR-1. Rather, it inhibits the binding of MCR-1 to substrates by binding to amino acids in the active region of MCR-1, thus inhibiting the biological activity of MCR-1 and its mutants (such as MCR-3). An in vivo mouse systemic infection model, pogostone in combination with colistin resulted in 80.0% (the survival rates after monotherapy with colistin or pogostone alone were 33.3% and 40.0%) survival at 72 h after infection of MCR-1-positve Escherichia coli (E. coli) ZJ487 (blaNDM-1-carrying), and pogostone in combination with colistin led to one or more order of magnitude decreases in the bacterial burdens in the liver, spleen and kidney compared with pogostone or colistin alone. Our results confirm that pogostone is a potential inhibitor of MCR-1 for use in combination with polymyxin for the treatment of severe infections caused by MCR-1-positive Enterobacteriaceae.


Subject(s)
Colistin , Escherichia coli Proteins , Animals , Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Drug Resistance, Bacterial , Escherichia coli , Escherichia coli Proteins/genetics , Mice , Microbial Sensitivity Tests , Oils, Volatile , Plasmids
7.
Microb Pathog ; 162: 105354, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34896203

ABSTRACT

Streptococcus suis (S. suis), an important zoonotic pathogenic bacterium, can cause multiple diseases and fatal infections in both humans and animals. The emergence of highly virulent and extensively drug-resistant strains of S. suis has raised questions about the efficacy of available therapeutic agents, thereby necessitating novel therapeutic strategies. Suilysin (SLY) is one of the most essential determinants of virulence for the pathogenicity of S. suis capsular type 2 (SS2). In addition, inhibiting the excessive inflammatory response is a strategy to reduce the damage caused by SS2 infection. In this study, we identified acacetin as an effective inhibitor of SLY, which inhibited the oligomerisation of SLY without affecting bacterial growth. Furthermore, the addition of 4-16 µg/ml acacetin to the co-infection system of the cells reduced S. suis-induced inflammation by downregulating the activation of the MAPK signalling pathway, thereby alleviating the S. suis-mediated cell injury. Thus, in addition to the conventional antibiotic therapy, acacetin represent a potential drug candidate and strategy for the treatment of S. suis infections as it simultaneously inhibited the haemolytic activity of SLY and downregulated the inflammatory response.


Subject(s)
Streptococcal Infections , Streptococcus suis , Animals , Flavones , Hemolysin Proteins , Humans , Inflammation/drug therapy , Streptococcal Infections/drug therapy , Virulence
8.
J Med Chem ; 65(1): 857-875, 2022 01 13.
Article in English | MEDLINE | ID: mdl-34958208

ABSTRACT

Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51, which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo. In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclinical studies.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Leukemia, Myeloid, Acute/drug therapy , Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors , Animals , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Discovery , Female , High-Throughput Screening Assays , Humans , Mice , Mice, Inbred BALB C , Models, Molecular , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Substrate Specificity
9.
Biomed Res Int ; 2021: 9983988, 2021.
Article in English | MEDLINE | ID: mdl-34258289

ABSTRACT

OBJECTIVE: To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. METHODS: Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia (T 0), after anesthesia (T 1), and after surgery (T 2). RESULTS: Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T 1 by comparison with those of T 0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). CONCLUSION: Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.


Subject(s)
Anesthesia, Inhalation , Anesthesia, Intravenous/methods , Enzymes/blood , Hemodynamics/drug effects , Hysterectomy/methods , Myocardium/enzymology , Sevoflurane/administration & dosage , Aged , Biomarkers , Electrocardiography , Female , Humans , Hydrocortisone/blood , Middle Aged , Pattern Recognition, Automated , Postanesthesia Nursing
10.
Med Phys ; 48(9): 4872-4882, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34042185

ABSTRACT

PURPOSE: Lymphovascular invasion (LVI) and perineural invasion (PNI) are independent prognostic factors in patients with colorectal cancer (CRC). In this study, we aimed to develop and validate a preoperative predictive model based on high-throughput radiomic features and clinical factors for accurate prediction of LVI/PNI in these patients. METHODS: Two hundred and sixty-three patients who underwent colorectal resection for histologically confirmed CRC between 1 February 2011 and 30 June 2020 were retrospectively enrolled. Between 1 February 2011 and 30 September 2018, 213 patients were randomly divided into a training cohort (n = 149) and a validation cohort (n = 64) by a ratio of 7:3. We used a 10000-iteration bootstrap analysis to estimate the prediction error and confidence interval for two cohorts. The independent test cohort consisted of 50 patients between 1 October 2018 and 30 June 2020. Regions of interest (ROIs) were manually delineated in high-resolution T2-weighted and diffusion-weighted images using ITK-SNAP software on each CRC tumor slice. In total, 3356 radiomic features were extracted from each ROI. Next, we used the maximum relevance minimum redundancy and least absolute shrinkage and selection operator algorithms to select the strongest of these features to establish a clinical-radiomics model for predicting LVI/PNI. Receiver-operating characteristic and calibration curves were then plotted to evaluate the predictive performance of the model in the training, validation, and independent test cohorts. RESULTS: A multiparametric clinical-radiomics model combining MRI-reported extramural vascular invasion (EMVI) status and a Radiomics score for the LVI/PNI estimation was established. This model had significant predictive power in the training cohort (area under the curve [AUC] 0.91; 95% confidence interval [CI]: 0.85-0.97), validation cohort (AUC: 0.88; 95% CI: 0.79-89), and independent test cohorts (AUC 0.83, 95% CI 0.72-0.95). The model performed well in the independent test cohort with sensitivity of 0.818, specificity of 0.714, and accuracy of 0.760. Calibration curve and decision curve analysis demonstrated clinical benefits. CONCLUSION: Multiparametric clinical-radiomics models can accurately predict LVI/PNI in patients with CRC. Our model has predictive ability that should improve preoperative diagnostic performance and allow more individualized treatment decisions.


Subject(s)
Colorectal Neoplasms , Nomograms , Algorithms , Colorectal Neoplasms/diagnostic imaging , Humans , Magnetic Resonance Imaging , Retrospective Studies
12.
ACS Appl Mater Interfaces ; 13(3): 3949-3958, 2021 Jan 27.
Article in English | MEDLINE | ID: mdl-33428847

ABSTRACT

The design and development of carbon materials with high-efficiency oxygen reduction activity is still a problem. Folic acid (FA) has unique structural characteristics, and it can provide multiple coordination sites for metal ions. Here, folic acid (FA) was used as a metal complex ligand, and Cu-Co-based N-doped porous carbon nanosheets (Cu-CoNCNs) were synthesized by the solvothermal method, the molten salt template-assisted calcination method, and the chemical etching method. The Cu-CoNCNs synthesized by this method have highly efficient oxygen reduction reaction (ORR) activity. In 0.1 mol/L KOH electrolytes, the catalyst exhibits excellent ORR activity and has a fairly high half-wave potential (0.905 V vs reversible hydrogen electrode (RHE)). X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, infrared spectroscopy, and X-ray diffraction (XRD) were used to investigate the reasons why the catalyst has excellent catalytic activity and long-life stability. It was proved that the impressive ORR activity of Cu-CoNCNs comes from Cu doping, which can regulate the surface electronic structure of the catalyst, thereby optimizing the binding ability between the intermediate and adsorbed species and improving the catalytic activity.

13.
J Anim Physiol Anim Nutr (Berl) ; 105(1): 183-190, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32865324

ABSTRACT

Palmatine has a wide range of pharmacological effects and anti-inflammatory function. However, the effect of palmatine on LPS-induced inflammatory response of mammary epithelial cells has not been reported. In this research, we studied the anti-inflammatory mechanism of palmatine in EpH4-Ev (mouse mammary epithelial cells). EpH4-Ev cells were pre-treated with palmatine and then incubated with LPS. Cells were collected for examining production of pro-inflammatory mediators by qRT-PCR, and the related inflammatory signalling pathway was detected through immunofluorescence and Western blot. The results found that palmatine could significantly reduce the expression of IL-6, TNF-α, IL-1ß and COX-2 in EpH4-Ev cells. Research on mechanisms found that palmatine could significantly inhibit the protein levels of p-Akt, p-P65, p-ERK1/2 and p-P38 in EpH4-Ev cells. In conclusion, these data suggested that palmatine inhibits inflammatory response in LPS-induced EpH4-Ev cells via down-regulating Akt/ NF-кB, ERK1/2 and P38 signalling pathways.


Subject(s)
Lipopolysaccharides , Proto-Oncogene Proteins c-akt , Animals , Berberine Alkaloids , Epithelial Cells/metabolism , Lipopolysaccharides/toxicity , MAP Kinase Signaling System , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism
14.
Aging (Albany NY) ; 12(14): 14050-14065, 2020 07 23.
Article in English | MEDLINE | ID: mdl-32702668

ABSTRACT

Mastitis can seriously damage the physical and mental health of lactating women. The use of antibiotics and anti-inflammatory drugs may damage the flora balance in lactating women. To alleviate mastitis in lactating women and reduce drug-induced damage to the flora, we found that dehydroandrographolide (Deh) has good anti-inflammatory and bacterial balance functions. In vivo, we found that Deh significantly inhibited the expression of MPO, IL6, IL-1ß, TNF-α, COX2 and iNOS and reduced pathological damage to the mammary gland. The feces in the control and Deh groups were collected and sequenced for 16S flora. The results showed that Deh did not change the primary intestinal microflora composition of the two groups. In vitro, our study showed that Deh significantly inhibited the expression of IL6, IL-1ß and TNF-α in the EpH4-Ev cell line. When an AMPK inhibitor was added, the anti-inflammatory effect of Deh was blocked. To further study the anti-inflammatory mechanism of Deh, we found that Deh significantly promoted autophagy through the phosphorylation of AMPK, Beclin and ULK1. In conclusion, our study found that Deh promoted autophagy and played an anti-inflammatory role by activating the AMPK/Beclin/ULK1 signaling pathway and did not affect intestinal flora.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Autophagy/drug effects , Diterpenes/therapeutic use , Gastrointestinal Microbiome/drug effects , Mastitis/drug therapy , Mastitis/pathology , AMP-Activated Protein Kinases/antagonists & inhibitors , Animals , Autophagy-Related Protein-1 Homolog/drug effects , Beclin-1/drug effects , Cell Line , Cytokines/antagonists & inhibitors , Cytokines/biosynthesis , Diterpenes/antagonists & inhibitors , Female , Gene Expression Regulation/drug effects , Humans , Mice , Mice, Inbred ICR , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects
15.
Future Med Chem ; 12(12): 1121-1136, 2020 06.
Article in English | MEDLINE | ID: mdl-32400188

ABSTRACT

Aim: CDK4 and 6 are the key initiators in the transition from G1 to S phase in the cell cycle; thus, inhibition of CDK4/6 is a promising strategy for cancer treatment. Materials & methods: The Specs database and an in-house library were screened via the pharmacophore model and LibDock protocol and then the retrieved hits were clustered into 100 clusters. The CDK4/6 inhibitory activity of selected compounds was evaluated by CDK enzymatic assays, followed by chemical optimization of the top hit compound. Results & conclusion: The integration of pharmacophores and molecular docking offered us an effective method to discover the novel CDK4/6 inhibitor 10 and further chemical optimization led to the highly selective and potent CDK4/6 inhibitor 18, which exhibited potential for the treatment of multiple myeloma.


Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Drug Discovery , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/metabolism , Drug Evaluation, Preclinical , Drug Screening Assays, Antitumor , Humans , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Tumor Cells, Cultured
16.
Bioorg Med Chem ; 28(7): 115372, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32088124

ABSTRACT

Histone-lysine N-methyltransferase SET7 emerged as a potential target for multiple cancers. In a virtual screening program used to explore new and potent inhibitors of SET7, compound 16 was discovered as a top hit with an IC50 value of 6.02 µM. A further similarity search afforded a new compound 23, which exhibited better activity against SET7 with an IC50 value of 1.96 µM. Importantly, compound 23 selectively inhibited the proliferation of MV4-11 cells. Comprehensively, compound 23 can serve as a lead for further identification and development of more potent SET7 inhibitors.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Discovery , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Antineoplastic Agents/chemistry , Catalytic Domain , Cell Line, Tumor , Cell Survival/drug effects , Computational Chemistry , Computer Simulation , Escherichia coli/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Humans , Molecular Structure , Protein Binding , Protein Conformation , Structure-Activity Relationship
17.
J Nanobiotechnology ; 16(1): 83, 2018 Oct 27.
Article in English | MEDLINE | ID: mdl-30368238

ABSTRACT

BACKGROUND: In order to explore the possibility of treating breast cancer by local photo-therapy, a photothermal agents loaded in situ hydrogel was established. In detail, The Cu2MnS2 nanoplates were prepared by one-pot synthesis and, the thermosensitive Pluronic F127 was used as the hydrogel matrix. The Cu2MnS2 nanoplates and the hydrogel were characterized by morphous, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation as well as the rheology features. The therapeutic effects of the Cu2MnS2 nanoplates and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in tumor bearing mouse model. RESULTS: The Cu2MnS2 nanoplates with a diameter of about 35 nm exhibited satisfying serum stability, photo-heat conversion ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanoplates loaded in situ hydrogel shows a phase transition at body temperature and, as a result, a long retention in vivo. CONCLUSIONS: The photothermal agent embedded hydrogel played a promising photothermal therapeutic effects in tumor bearing mouse model with low systemic toxicity after peritumoral administration.


Subject(s)
Copper/chemistry , Hydrogels/chemistry , Hyperthermia, Induced , Injections , Mammary Neoplasms, Animal/therapy , Manganese/chemistry , Nanoparticles/chemistry , Phototherapy , Sulfides/chemistry , Animals , Cell Line, Tumor , Female , Mammary Neoplasms, Animal/pathology , Mice, Inbred BALB C , Nanoparticles/ultrastructure , Poloxamer/chemistry
18.
Medicine (Baltimore) ; 97(42): e12913, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30335022

ABSTRACT

Acute appendicitis (AA) affects between 7% and 8% of the world population and is one of the most common general surgical emergencies. The concept of seasonal patterns in the incidence of AA remains controversial. Thus, this study aimed to investigate whether meteorological factors are related to variations in the rate of pediatric AA cases at the Children's Hospital in Chongqing, China.In total, in this retrospective survey, 3436 children younger than 18 years who had been hospitalized with AA from January 1, 2008 to December 31, 2013 were enrolled, and the meteorological factors during this period were collected.Patients with AA showed a male/female ratio of 1.81:1; the highest incidence age ranged from 6 to 12 years old (P < .0001). The highest incidences of pediatric AA occurred in summer and autumn, with a peak in September and a trough in February. Pearson correlation analysis showed that the monthly mean temperature (r = 0.357, P = .001), monthly mean relative humidity (r = -0.357, P = .001), and monthly mean sunshine duration (r = 0.235, P = -0.031) were relatively weak correlated with pediatric AA. Multiple linear regression analysis indicated that pediatric AA occurrence was positively affected by monthly mean temperature (P < .0001) and negatively affected by monthly mean humidity (P < .0001) and monthly sum of sunshine (P < .0001), while monthly mean air pressure (P = .092), monthly wind speed (P = .143) and monthly precipitation (P = .297) were marginally associated with pediatric AA.Pediatric AA is associated with climatic factors. Specifically, pediatric AA is more likely related to the following meteorological conditions of: high temperature (20 °C-30 °C), low humidity, and less sunshine.


Subject(s)
Appendicitis/etiology , Meteorological Concepts , Acute Disease , Adolescent , Appendicitis/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Humidity , Incidence , Infant , Infant, Newborn , Linear Models , Male , Retrospective Studies , Sunlight , Temperature , Time Factors , Wind
19.
Chin Med J (Engl) ; 128(22): 2988-97, 2015 Nov 20.
Article in English | MEDLINE | ID: mdl-26608976

ABSTRACT

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. METHODS: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. RESULTS: A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. CONCLUSIONS: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Methylphenidate/therapeutic use , Administration, Oral , Attention Deficit Disorder with Hyperactivity/physiopathology , Child , Cognition/drug effects , Female , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Neuropsychological Tests , Prospective Studies , Treatment Outcome
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 36(9): 949-52, 2015 Sep.
Article in Chinese | MEDLINE | ID: mdl-26814860

ABSTRACT

OBJECTIVE: To explore the relationship between mothers' body mass index (BMI) before pregnancy or weight gain during pregnancy and autism in children. METHODS: From 2013 to 2014, the 181 children with autism and 181 healthy children matched by sex and age from same area were included in this study. According to mothers' BMI before pregnancy, the selected cases were divided into 3 groups: low, normal and high group. Then 3 groups were divided into 3 subgroups based on mother' s weight gain during pregnancy: low, normal and high group, according to the recommendations of Institute of Medicine. Logistic regression analysis and χ(2) test were conducted with SPSS 18.0 software to analysis the relationship between mothers' BMI before pregnancy or weight gain during pregnancy and autism in children. RESULTS: The age and sex distributions of case group and control group were consistent (χ(2)=0.434, P>0.05). The mothers' BMI before pregnancy of case group was higher than that of control group (χ(2)=9.580, P<0.05) ,which was (21.28±3.80) kg/m(2) for case group and (19.87±2.83) kg/m(2) for control group. The proportion of cases in high BMI group (10.5%) was much higher than that in control group (2.8%) . The risk of children with autism in high BMI group was 3.7 times higher than that in normal BMI group (OR=3.71, 95% CI: 1.34-10.24). In normal BMI group, the proportion of mothers who had excessive weight gain during pregnancy was higher in case group (44.1%) than in control group (33.9%). In high BMI group, the proportion of mothers who had excessive weight gain was higher in case group (52.6%) than in control group (20.0%) . In normal BMI group (χ(2) =8.690, P<0.05) and high BMI group (χ(2)=4.775, P<0.05), the weight gain during pregnancy was associated with autism in children. Logistic regression analysis showed that mothers' BMI before pregnancy (unadjusted OR=1.89, 95% CI: 1.26-2.85, adjusted OR=1.52, 95% CI: 1.19-2.27) and weight gain during pregnancy were the risk factors for autism in children (unadjusted OR=1.63, 95% CI: 1.08-1.25, adjusted OR=1.64, 95% CI: 1.21-2.21). CONCLUSION: Overweight or obesity before pregnancy and excessive weight gain during pregnancy were associated with autism in children, suggesting that women who plan to be pregnant should pay attention to body weight control.


Subject(s)
Autistic Disorder , Body Mass Index , Mothers , Weight Gain/ethnology , Child , Female , Humans , Obesity , Overweight , Pregnancy , Risk Factors , United States
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