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1.
Ann Surg Oncol ; 31(1): 58-65, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37833463

ABSTRACT

BACKGROUND: Comparative studies evaluating quality of care in different healthcare systems can guide reform initiatives. This study seeks to characterize best practices by comparing utilization and outcomes for patients with pancreatic cancer (PC) in the USA and Ontario, Canada. METHODS: Patients (age ≥ 66 years) with PC were identified from the Ontario Cancer Registry and SEER-Medicare databases from 2006 to 2015. Demographics and treatment (surgery, radiation, chemotherapy, or multimodality (surgery and chemotherapy)) were described. In resected patients, neoadjuvant therapy, readmission, and 30- and 90-day postoperative mortality rates were calculated. Survival was assessed using Kaplan-Meier curves. RESULTS: This study includes 38,858 and 11,512 patients with PC from the USA and Ontario, respectively. More female patients were identified in the USA (54.0%) versus Ontario (46.9%). In the entire cohort, US patients received more radiation in addition to other therapies (18.8% vs. 13.5% Ontario) and chemotherapy alone (34.3% vs. 19.0% Ontario). While rates of resection were similar (13.4% USA vs.12.5% Ontario), multimodality therapy was more common in the UAS (9.0% vs. 6.4%). Among resected patients, neoadjuvant chemotherapy was uncommon in both groups, although more frequent in the USA (12.0% vs. 3.2% Ontario). The 30- and 90-day postoperative mortality rates were lower in Ontario vs. the USA (30-day: 3.26% vs. 4.91%; 90-day: 7.08% vs. 10.96%), however, overall survival was similar between the USA and Ontario. CONCLUSIONS: We observed substantive differences in treatment and outcomes between PC patients in the USA and Ontario, which may reflect known differences in healthcare systems. Close evaluation of healthcare policies can inform initiatives to improve care quality.


Subject(s)
National Health Programs , Pancreatic Neoplasms , Humans , Female , Aged , Ontario/epidemiology , Combined Modality Therapy , Registries , Pancreatic Neoplasms/drug therapy , Neoadjuvant Therapy , Retrospective Studies
2.
Acc Chem Res ; 55(18): 2545-2561, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36083117

ABSTRACT

Enantiopure atropisomers have become increasingly important in asymmetric synthesis and catalysis, pharmaceutical science, and material science since the discovery of inherent features of axial chirality originating from rotational restriction. Despite the advances made in this field to date, it remains highly desirable to construct structurally diverse atropisomers with potentially useful functions. We propose superposition to match axial and point chirality as a potentially useful strategy to access structurally complex and diverse building blocks for organic synthesis and pharmaceutical science because merging atropisomeric backbones with one or more extra chiral elements can topologically broaden three-dimensional environments to create complex scaffolds with multiple tunable parameters. Over the past decade, we have successfully implemented a strategic design for the superposition of axial and point chirality to develop a series of enantiopure atropisomers and have utilized the synergistic functions of these molecules to enhance chirality transfer in various catalytic asymmetric transformations.In this Account, we present several novel atropisomers with superposed axial and point chirality developed in our laboratory. In our studies, this superposition strategy was used to design and synthesize both biaryl and non-biaryl atropisomers from commercially available chiral sources. Consequently, these atropisomers were used to demonstrate the importance of the synergetic functions of axial and point chirality in specific enantioselective reactions. For example, aromatic amide-derived atropisomers, simplified as Xing-Phos arrays, were broadly employed in Ag-catalyzed [3 + 2] cycloaddition by a series of reactions of aldiminoesters with activated alkenes and imines, as well as being used as chiral solvating agents for the discrimination of optically active mandelic acid derivatives. Considering the powerful potential of non-biaryl atropisomers for asymmetric catalysis, we also explored the transition-metal-catalyzed enantioselective construction of a novel backbone of non-biaryl atropisomers (Ar-alkene, Ar-N axis) bearing both axial and point chirality for the design and synthesis of chiral ligands and functional molecules.The studies presented herein are expected to stimulate further research efforts on the development of functional atropisomers by superposition of matching axial and point chirality. In addition to tunable electron and stereohindrance effects, the synergy between matching chiral elements of axial/point chirality and functional groups is proven to be a special function that cannot be ignored for promoting reactivity and chirality-transfer efficiency in enantioselective synthesis. Consequently, our novel types of scaffolds with superposed axial and point chirality that are capable of versatile coordination with various metal catalysts in asymmetric catalysis highlight the power of the superposition of matching axial and point chirality for the construction of synthetically useful atropisomers.


Subject(s)
Alkenes , Imines , Amides , Pharmaceutical Preparations , Stereoisomerism
3.
Opt Express ; 31(2): 3390-3400, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36785333

ABSTRACT

Compressive ghost imaging (CGI) can effectively reduce the number of measurements required for ghost imaging reconstruction. In most cases, however, when using illumination patterns as measurement matrices, CGI has not demonstrated the ability to reconstruct high-quality images at an ultra-low sampling rate as perfect as claimed by compressive sensing theory. According to our analysis, the reason is that the non-negative nature of light intensity causes measurement matrix in compressive ghost imaging to be inconsistent with the essential requirements of good measurement matrix in compressive sensing theory, leading to low reconstruction quality. Aiming at this point, we propose a bipolar compressive ghost imaging method to improve the reconstruction quality of ghost imaging. The validity of the proposed method is proven by simulations and experiments.

4.
J Environ Manage ; 348: 119306, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37839204

ABSTRACT

Research studies on nutrient content and microbial communities after the application of organic manure have been reported, while available information about multi-interaction mechanisms of nutrient stoichiometry and microbial succession in soil aggregates remains limited. This work conducted a 10-year field experiment amended with cow manure (1.5 t/ha), during which the application of organic manure stimulated the fragmentation of soil macro-aggregates (>5 mm) and the agglomeration of soil micro-aggregates (<0.25 mm). Hence, the proportion of medium-size aggregates (0.25-5 mm) was increased in bulk soil, and there was an insignificant difference in the stability of soil aggregates. Meanwhile, the application of organic manure increased soil organic carbon (SOC), total nitrogen (TN) and phosphorus (TP) in all soil aggregate fractions. SOC, TN and TP were higher in micro-aggregates (<0.25 mm) after the application of organic manure, thus the dominating phylum of bacteria and fungi was more abundance in micro-aggregates due to the increase in nutrient level. During the organic fertilization process, fungal communities significantly changed because the variation of carbon-to-nitrogen ratio (C:N) in soil aggregates. Cultivated farmland in Northeast China showed a considerable capacity to sequestrate SOC during the organic fertilization process, but nitrogen may be a primary macro-element limiting soil productivity. Theoretically, organic manure amended with nitrogen fertilizer could be an effective measure to maintain microbial diversity and crop productivity in agro-ecosystems in Northeast China.


Subject(s)
Microbiota , Soil , Carbon/analysis , Manure , Fertilizers/analysis , Nitrogen/analysis , China , Fertilization , Soil Microbiology , Agriculture
5.
BMC Nurs ; 22(1): 250, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37507706

ABSTRACT

OBJECTIVE: To translate the career success in nursing scale (CSNS) into Chinese and evaluate its psychometric properties. BACKGROUND: A lower sense of career success seriously affects the enthusiasm of nurses and increases their turnover rate. Therefore, an accurate assessment of the career success level of nurses is necessary. However, China does not have a professional tool for assessing the career success of nurses. METHODS: The stratified sampling method was used to recruit participants from 22 hospitals of different grades in 5 cities in China. A total of 650 and 348 subjects were selected for item analysis and reliability and validity tests, respectively, of the translated initial scale. RESULTS: The Chinese version of the CSNS (C-CSNS) with 33 items had good psychometric properties. Cronbach's α was 0.960, split-half reliability was 0.893, and ICC within two weeks was 0.981. Exploratory factor analysis extracted 5 common factors that explained 63.73% of the total variance, and confirmatory factor analysis supported acceptable construct validity. CONCLUSION: The C-CSNS has adequate construct validity and excellent psychometric properties and can be used for accurate assessment of nurses' career success. IMPLICATIONS FOR NURSING MANAGEMENT: A new tool that is more suitable for the Chinese hospital nursing context is available for evaluating Chinese clinical nurses' career success. Nursing managers can formulate appropriate management strategies according to the evaluation results to assist nurses in career development planning, thereby improving their career success level.

6.
Appl Opt ; 61(4): 1022-1029, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35201070

ABSTRACT

We present a new color computational ghost imaging strategy using a sole single-pixel detector and training by simulated dataset, which can eliminate the actual workload of acquiring experimental training datasets and reduce the sampling times for imaging experiments. First, the relative responsibility of the color computational ghost imaging device to different color channels is experimentally detected, and then enough data sets are simulated for training the neural network based on the response value. Because the simulation process is much simpler than the actual experiment, and the training set can be almost unlimited, the trained network model has good generalization. In the experiment with a sampling rate of only 4.1%, the trained neural network model can still recover the image information from the blurry ghost image, correct the color distortion of the image, and get a better reconstruction result. In addition, with the increase in the sampling rate, the details and color characteristics of the reconstruction result become better and better. Feasibility and stability of the proposed method have been verified by the reconstruction results of the trained network model on the color objects of different complexities.


Subject(s)
Deep Learning , Diagnostic Imaging , Image Processing, Computer-Assisted/methods , Neural Networks, Computer
7.
Molecules ; 27(17)2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36080360

ABSTRACT

Background: Targeting the CD47/SIRPα signaling pathway represents a novel approach to enhance anti-tumor immunity. However, the crystal structure of the CD47/SIRPα has not been fully studied. This study aims to analyze the structure interface of the complex of CD47 and IMM01, a novel recombinant SIRPα-Fc fusion protein. Methods: IMM01-Fab/CD47 complex was crystalized, and diffraction images were collected. The complex structure was determined by molecular replacement using the program PHASER with the CD47-SIRPαv2 structure (PDB code 2JJT) as a search model. The model was manually built using the COOT program and refined using TLS parameters in REFMAC from the CCP4 program suite. Results: Crystallization and structure determination analysis of the interface of IMM01/CD47 structure demonstrated CD47 surface buried by IMM01. Comparison with the literature structure (PDB ID 2JJT) showed that the interactions of IMM01/CD47 structure are the same. All the hydrogen bonds that appear in the literature structure are also present in the IMM01/CD47 structure. These common hydrogen bonds are stable under different crystal packing styles, suggesting that these hydrogen bonds are important for protein binding. In the structure of human CD47 in complex with human SIRPα, except SER66, the amino acids that form hydrogen bonds are all conserved. Furthermore, comparing with the structure of PDB ID 2JJT, the salt bridge interaction from IMM01/CD47 structure are very similar, except the salt bridge bond between LYS53 in IMM01 and GLU106 in CD47, which only occurs between the B and D chains. However, as the side chain conformation of LYS53 in chain A is slightly different, the salt bridge bond is absent between the A and C chains. At this site between chain A and chain C, there are a salt bridge bond between LYS53 (A) and GLU104 (C) and a salt bridge bond between HIS56 (A) and GLU106 (C) instead. According to the sequence alignment results of SIRPα, SIRPß and SIRPγ in the literature of PDB ID 2JJT, except ASP100, the amino acids that form common salt bridge bonds are all conserved. Conclusion: Our data demonstrated crystal structure of the IMM01/CD47 complex and provides a structural basis for the structural binding interface and future clinical applications.


Subject(s)
Amino Acids , Antigens, Differentiation , CD47 Antigen , Receptors, Immunologic , Amino Acids/chemistry , Antigens, Differentiation/chemistry , CD47 Antigen/chemistry , Humans , Phagocytosis , Protein Binding , Receptors, Immunologic/chemistry , Recombinant Fusion Proteins/chemistry
8.
Opt Lett ; 46(8): 1840-1843, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33857083

ABSTRACT

A novel, to the best of our knowledge, color computational ghost imaging scheme is presented for the reconstruction of a color object image, which greatly simplifies the experimental setup and shortens the acquisition time. Compared to conventional schemes, it only adopts one digital light projector to project color speckles and one single-pixel detector to receive the light intensity, instead of utilizing three monochromatic paths separately and synthesizing the three branch results. Severe noise and color distortion, which are common in ghost imaging, can be removed by the utilization of a generative adversarial network, because it has advantages in restoring the image's texture details and generating the image's match to a human's subjective feelings over other generative models in deep learning. The final results can perform consistently better visual quality with more realistic and natural textures, even at the low sampling rate of 0.05.

9.
J Virol ; 93(7)2019 04 01.
Article in English | MEDLINE | ID: mdl-30700601

ABSTRACT

The presence of sequence divergence through adaptive mutations in the major capsid protein VP1, and also in VP0 (VP4 and VP2) and VP3, of foot-and-mouth disease virus (FMDV) is relevant to a broad range of viral characteristics. To explore the potential role of isolate-specific residues in the VP0 and VP3 coding regions of PanAsia-1 strains in genetic and phenotypic properties of FMDV, a series of recombinant full-length genomic clones were constructed using Cathay topotype infectious cDNA as the original backbone. The deleterious and compensatory effects of individual amino acid substitutions at positions 4008 and 3060 and in several different domains of VP2 illustrated that the chain-based spatial interaction patterns of VP1, VP2, and VP3 (VP1-3), as well as between the internal VP4 and the three external capsid proteins of FMDV, might contribute to the assembly of eventually viable viruses. The Y2079H site-directed mutants dramatically induced a decrease in plaque size on BHK-21 cells and viral pathogenicity in suckling mice. Remarkably, the 2079H-encoding viruses displayed a moderate increase in acid sensitivity correlated with NH4Cl resistance compared to the Y2079-encoding viruses. Interestingly, none of all the 16 rescued viruses were able to infect heparan sulfate-expressing CHO-K1 cells. However, viral infection in BHK-21 cells was facilitated by utilizing non-integrin-dependent, heparin-sensitive receptor(s) and replacements of four uncharged amino acids at position 3174 in VP3 of FMDV had no apparent influence on heparin affinity. These results provide particular insights into the correlation of evolutionary biology with genetic diversity in adapting populations of FMDV.IMPORTANCE The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading effects on the viability and developmental characteristics of progeny viruses. Y2079H in VP0 of the indicated FMDVs could affect plaque size and pathogenicity, as well as acid sensitivity correlated with NH4Cl resistance, whereas there was no inevitable correlation in viral plaque and acid-sensitive phenotypes. The high affinity of non-integrin-dependent FMDVs for heparin might be explained by the differences in structures of heparan sulfate proteoglycans on the surfaces of different cell lines. These results may contribute to our understanding of the distinct phenotypic properties of FMDV in vitro and in vivo.


Subject(s)
Amino Acid Substitution/genetics , Capsid Proteins/genetics , Foot-and-Mouth Disease Virus/genetics , Foot-and-Mouth Disease/virology , Animals , CHO Cells , Cricetulus , Heparitin Sulfate/genetics , Mice , Open Reading Frames/genetics , Serogroup , Virion/genetics
11.
BMC Psychiatry ; 19(1): 330, 2019 10 30.
Article in English | MEDLINE | ID: mdl-31666033

ABSTRACT

BACKGROUND: Increasing attention has been paid to differences in the prevalence of perinatal depression by HIV status, although inconsistent results have been reported. The aim of this systematic review and meta-analysis was to assess the relationship between perinatal depression and HIV infection. A comprehensive meta-analysis of comparative studies comparing the prevalence of antenatal or postnatal depression between HIV-infected women and HIV-negative controls was conducted. METHODS: Studies were identified through PubMed/Medline, Scopus, Web of Science, Cochrane Library, Embase and PsycINFO, and the reading of complementary references in August 2019. Subgroup analyses were performed for anticipated explanation of heterogeneity using methodological quality and pre-defined study characteristics, including study design, geographical location and depression screening tools for depression. The overall odds ratio (OR) and mean prevalence of each group were calculated. RESULTS: Twenty-three studies (from 21 publications), thirteen regarding antenatal depression and ten regarding postnatal depression were included, comprising 3165 subjects with HIV infection and 6518 controls. The mean prevalence of antenatal depressive symptoms in thirteen included studies was 36% (95% CI: 27, 45%) in the HIV-positive group and 26% (95% CI: 20, 32%) in the control group. The mean prevalence of postnatal depressive symptoms in ten included studies was 21% (95% CI: 14, 27%) in the HIV-positive group and 16% (95% CI: 10, 22%) in the control group. Women living with HIV have higher odds of antenatal (OR: 1.42; 95% CI: 1.12, 1.80) and postnatal depressive symptoms (OR: 1.58; 95% CI: 1.08, 2.32) compared with controls. Publication bias and moderate heterogeneity existed in the overall meta-analysis, and heterogeneity was partly explained by the subgroup analyses. CONCLUSIONS: Women with HIV infection exhibit a significantly higher OR of antenatal and postnatal depressive symptoms compared with controls. For the health of both mother and child, clinicians should be aware of the significance of depression screening before and after delivery in this particular population and take effective measures to address depression among these women.


Subject(s)
Depression, Postpartum/epidemiology , Depression/epidemiology , HIV Infections/epidemiology , Pregnancy Complications/epidemiology , Comorbidity , Female , Humans , Pregnancy , Prevalence
12.
Chemistry ; 24(21): 5644-5651, 2018 Apr 11.
Article in English | MEDLINE | ID: mdl-29412481

ABSTRACT

The first catalytic asymmetric synthesis of highly functionalized pentafluorosulfanylated pyrrolidines is described. The method, based on a 1,3-dipolar cycloaddition reaction of aryl and heteroaryl-substituted glycine Schiff bases with pentafluorosulfanyl acrylic esters, gave access to a broad range of pyrrolidines bearing aryl, naphtyl, and heteroaryl groups. By using Xing-Phos as a catalyst, the corresponding products were obtained in good yields, good to high regioselectivity, and excellent diastereo- and enantioselectivities (up to 98 % ee). This methodology allowed the preparation of enantioenriched SF5 compounds for the first time using an enantioselective approach.


Subject(s)
Hydrocarbons, Fluorinated/chemical synthesis , Pyrrolidines/chemical synthesis , Sulfur Compounds/chemical synthesis , Catalysis , Cycloaddition Reaction , Hydrocarbons, Fluorinated/chemistry , Molecular Structure , Pyrrolidines/chemistry , Stereoisomerism , Sulfur Compounds/chemistry
13.
Water Sci Technol ; 77(3-4): 829-837, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29431728

ABSTRACT

In this study, the influence of vegetation type and environmental temperature on performance of constructed wetlands (CWs) was investigated. Results of vegetation types indicated that the removal of most nutrients in polyculture was greater than those in monoculture and unplanted control. The greatest removal percentages of NH4+-N, total nitrogen (TN) and total phosphorus (TP) in polyculture were 98.7%, 98.5%, and 92.6%, respectively. In experiments of different temperatures, the removal percentages of NH4+-N, NO3--N, TN and TP in all CWs tended to decrease with the decline of temperature. Especially, a sharp decline in the removal percentages of NO3--N (decreased by above 13.8%) and TN (decreased by above 7.9%) of all CWs was observed at low temperature (average temperature of 8.9 °C). Overall, the performance of CWs was obviously influenced by temperature, and the polyculture still showed best performance in the removal of nitrogen when the average temperature dropped to 19.8 °C. Additionally, the variations of urease activities in rhizosphere soil tended to decrease with the decreasing temperature. Overall, a substantial enhancement for nitrogen and TP removal in polyculture (Canna indica + Lythrum salicaria) was observed. In conclusion, CW cultivated with polyculture was a good strategy for enhancing nutrient removal when temperature was above 19.8 °C.


Subject(s)
Lythrum/metabolism , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/metabolism , Wetlands , Zingiberales/metabolism , Ammonium Compounds/metabolism , Biodegradation, Environmental , Nitrogen/metabolism , Phosphorus/metabolism , Temperature
14.
Chemistry ; 23(17): 4055-4059, 2017 Mar 23.
Article in English | MEDLINE | ID: mdl-28181312

ABSTRACT

Direct functionalization of terpyridines is an increasingly important topic in the field of dyes and catalysis as well as supramolecular chemistry, but its synthesis and transformation is usually challenging. Herein, a HOMO-raising strategy is reported for the construction of a super-stable novel terpyridine chromophores, in which the selective oxidation of terpyridines at its 3-position was determined successfully to the synthesis of phenol-functionalization of terpyridines (TPyOHs) bearing a hydrogen bonding group. The corresponding TPyOHs displayed strong aggregation-induced emission and exhibited highly selective and visual detection of ZnII cation with a record green terpyridine-based luminophore with nanomolar sensitivity (125 nm).

15.
Molecules ; 22(5)2017 May 18.
Article in English | MEDLINE | ID: mdl-28524100

ABSTRACT

It was found that 1,2-trifluoromethylation reactions of ketones, enones, and aldehydes were easily accomplished using the Prakash reagent in the presence of catalytic amounts of cesium carbonate, which represents an experimentally convenient, atom-economic process for this anionic trifluoromethylation of non-enolisable aldehydes and ketones.


Subject(s)
Carbonates/chemistry , Cesium/chemistry , Chalcones/chemistry , Ethers/chemical synthesis , Ketones/chemistry , Silanes/chemical synthesis , Aldehydes/chemistry , Catalysis , Chemistry Techniques, Synthetic , Halogenation , Methylation , Molecular Structure , Stereoisomerism
16.
Chemistry ; 22(30): 10399-404, 2016 Jul 18.
Article in English | MEDLINE | ID: mdl-27198615

ABSTRACT

The mechanism-oriented reaction design for the divergent synthesis of chiral molecules from simple starting materials is highly desirable. In this work, aromatic amide-derived nonbiarylatropisomer/silver (silver/Xing-Phos) complex was used to catalyze the Michael addition of glycine aldimino esters to chalcones and successfully applied to the subsequent cyclocondensation to afford substituted cis-Δ(1)-pyrroline derivatives with up to 98 % ee. Besides the inherent performance of the chiral Ag/Xing-Phos catalyst system, it was found that the workup of such reactions played an important role for the stereoselective construction of stereodivergent Δ(1)-pyrrolines, in which an epimerization of the cis-Δ(1)-pyrrolines to the trans-isomers during was revealed.

17.
Angew Chem Int Ed Engl ; 54(17): 5255-9, 2015 Apr 20.
Article in English | MEDLINE | ID: mdl-25728216

ABSTRACT

The synthesis of a series of aromatic amide-derived non-biaryl atropisomers with a phosphine group and multiple stereogenic centers is reported. The novel phosphine ligands exhibit high diastereo- and enantioselectivities (up to >99:1 d.r., 95-99 % ee) as well as yields in the silver-catalyzed asymmetric [3+2] cycloaddition of aldiminoesters with nitroalkenes, which provides a highly enantioselective strategy for the synthesis of optically pure nitro-substituted pyrrolidines. In addition, the experimental results with regard to the carbon stereogenic center as well as the amide stereochemistry confirmed the potential of hemilabile atropisomers as chiral ligand in catalytic asymmetric [3+2] cycloaddition reaction.

18.
BMC Vet Res ; 10: 2, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24386990

ABSTRACT

BACKGROUND: Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3. This study investigated the potential of R848 and poly(I:C) as an adjuvant 146S foot-and-mouth disease virus (FMDV) vaccine formulated with aluminum hydroxide (Al(OH)3). RESULTS: Antibody titers to FMDV and CD8+ T cells were markedly enhanced in mice immunized to 146S FMDV + Al(OH)3 + R848 + poly(I:C) compared with mice immunized to FMDV + ISA206. IFN-γ secretion substantially increased compared with IL-4 secretion by splenic T cells stimulated with FMDV antigens in vitro, suggesting that R848, poly(I:C), and with Al(OH)3 together biased the immune response toward a Th1-type direction. CONCLUSIONS: These results indicated that the R848 and poly(I:C) together with Al(OH)3 enhanced humoral and cellular immune responses to immunization with 146S FMDV antigens. Thus, this new vaccine formulation can be used for FMDV prevention.


Subject(s)
Adjuvants, Immunologic/pharmacology , Aluminum Hydroxide/pharmacology , Foot-and-Mouth Disease/prevention & control , Imidazoles/pharmacology , Poly I-C/pharmacology , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/chemistry , Animals , Antibodies, Viral/blood , Antibody Specificity , Female , Foot-and-Mouth Disease/immunology , Imidazoles/administration & dosage , Mice , Mice, Inbred BALB C , Poly I-C/administration & dosage , Spleen/cytology , Spleen/drug effects , T-Lymphocyte Subsets , Viral Vaccines/administration & dosage
19.
Aging (Albany NY) ; 16(4): 3386-3403, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38345573

ABSTRACT

BACKGROUND: Cisplatin (DDP) is one of the important chemotherapy drugs for patients with advanced gastric cancer and metastasis, but its resistance is a bottleneck problem that affects clinical efficacy and patient survival. Eremias multiocellata (EM) is a traditional Chinese herbal medicine, which has been used in the treatment of precancerous lesions, gastric cancer, liver fibrosis, and other digestive diseases. However, the mechanism of reducing chemotherapy resistance to gastric cancer is still unclear. METHODS: We used the MTT assay to evaluate the proliferative viability of gastric cancer parental cell line MKN45 and its drug-resistant cell line MKN45/DDP, and compared their drug-resistance indices. The migration and invasion abilities of MKN45/DDP drug-resistant cells were evaluated using the Transwell assay. Apoptosis in MKN45/DDP drug-resistant cells was detected using flow cytometry. The effect of a combination of EM and cisplatin on the levels of reactive oxygen species (ROS) and lipid peroxides (LPO) in cisplatin-resistant gastric cancer cells was detected using ROS fluorescent probes and a lipid peroxidation assay kit in conjunction with flow cytometry. The effect of EM combined with cisplatin on the level of iron ions was detected by fluorescence probe and confocal laser technique. Hematoxylin-eosin staining (HE staining) was used to detect the histopathologic morphology of drug-resistant gastric cancer in nude mice. Ferroptosis-related proteins were measured using immunohistochemistry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect tumor drug resistance-related genes. The NF-κB/Snail pathway-related proteins, PI3K/AKT/mTOR pathway-related proteins, and drug resistance-related proteins were detected by Western blot. RESULTS AND CONCLUSIONS: The results of in vitro and in vivo experiments showed that EM combined with DDP could effectively inhibit the migration and invasive ability of MKN45/DDP cells, as well as induce apoptosis of MKN45/DDP cells; the combination of the two drugs could significantly increase the levels of ROS, lipid peroxidation and divalent ferric ions in MKN45/DDP cells, at the same time reducing the levels of Ferroptosis-related proteins, which could induce Ferroptosis. In addition, EM combined with DDP can also exert the effect of reversing DDP resistance and increasing the sensitivity of gastric cancer drug-resistant cells to DDP by regulating the NF-κB/Snail signaling pathway, PI3K/AKT/mTOR signaling pathway, and the expression of drug resistance-related proteins and genes.


Subject(s)
Cisplatin , Stomach Neoplasms , Animals , Mice , Humans , Cisplatin/pharmacology , Cisplatin/therapeutic use , Stomach Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , NF-kappa B , Proto-Oncogene Proteins c-akt/metabolism , Mice, Nude , Phosphatidylinositol 3-Kinases , Reactive Oxygen Species , Apoptosis , TOR Serine-Threonine Kinases , Ions/pharmacology , Ions/therapeutic use , Cell Line, Tumor , Cell Proliferation
20.
Eur J Med Res ; 29(1): 443, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39217395

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear. OBJECTIVE: The intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed. SETTING AND DESIGN: To analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment. RESULTS: The results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1ß, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients. CONCLUSIONS: Dietary inulin may improve obese PCOS women disease through the gut flora-inflammation-steroid hormone pathway. THE CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17012281.


Subject(s)
Gastrointestinal Microbiome , Inulin , Obesity , Polycystic Ovary Syndrome , Adult , Female , Humans , Young Adult , Gastrointestinal Microbiome/drug effects , Inulin/pharmacology , Obesity/microbiology , Obesity/complications , Obesity/metabolism , Obesity/drug therapy , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/microbiology , Polycystic Ovary Syndrome/metabolism
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