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1.
J Fish Biol ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35567749

RESUMO

An 8-week feeding trial was carried out to investigate the effects of dietary nucleotides on growth performance, intestinal morphology, immune response and disease resistance of juvenile largemouth bass, Micropterus salmoides. Five grades of dietary nucleotides levels were designed as 0, 0.2, 0.4, 0.8, and 1.2 g/kg, respectively. Each group had 3 replicates with 40 fish in each replicate. After the feeding experiment, 15 fish from each tank were infected with Aeromonas hydrophila for 14 days. The results indicated that fish fed the diets containing 0.4 g/kg, 0.8 g/kg and 1.2 g/kg nucleotides had higher growth performance and feed utilization than those fed the control diet. However, there were no significant differences in survival between all the groups, although fish fed the diets with all level nucleotides obtained higher survival than those fed the control diet. Dietary nucleotides significantly affected the superoxide dismutase (SOD), acid phosphatase (ACP) and catalase (CAT) activity in serum, but not the malondialdehyde (MDA) content. Fish fed the 0.4 g/kg nucleotide diets had the highest fold height, enterocyte height and muscular layer thickness significantly. The average mortality of largemouth bass infected with Aeromonas hydrophila was significantly influenced by dietary nucleotides. The mortality were significantly higher in the control group (91.11%) and 0.02% nucleotide group (73.11%) followed by the other groups, and lowest in 0.8 g/kg nucleotide group. In summary, dietary 0.4 g/kg-0.8 g/kg nucleotides promoted growth performance, enhanced immunity and improved the intestinal morphology and disease resistance of largemouth bass. This article is protected by copyright. All rights reserved.

2.
Plant J ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506310

RESUMO

Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter root and less Pi content than the wild-type plant under LP. Moreover, a mutant of ABI5, the central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP. ABI5 facilitated phosphate acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpressing PHT1;1 completely rescued its reduced Pi content under LP. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in Arabidopsis response to phosphate deficiency.

4.
BMC Microbiol ; 22(1): 123, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513820

RESUMO

BACKGROUND: Haemophilus influenzae was the most aggressive pathogen and formed a major cause of bacterial meningitis and pneumonia in young children and infants, which need medical emergency requiring immediate diagnosis and treatment. However, From isolation to identification of H. influenzae, the traditional diagnose strategy was time-consuming and expensive. Therefore, the establishment of a convenient, highly sensitive, and stable detection system is urgent and critical. RESULTS: In this study, we used a combined method to detect H. influenzae. Six specific primers were designed on the basis of outer membrane protein P6 gene sequence of H. influenzae. The reaction condition such as the optimum temperature was 65℃, and the optimum reaction time was 30 min, respectively. Through the loop-mediated isothermal amplification (LAMP) in combination with nanoparticle-based lateral flow biosensor (LFB), the sensitivity of LAMP-LFB showed 100 fg was the lowest genomic DNA templates concentration in the pure cultures. Meanwhile, the specificity of H. influenzae-LAMP-LFB assay showed the exclusive positive results, which were detected in H. influenzae templates. In 55 clinical sputum samples, 22 samples were positive with LAMP-LFB method, which was in accordance with the traditional culture and Polymerase Chain Reaction (PCR) method. The accuracy in diagnosing H. influenzae with LAMP-LFB could reach 100%, compared to culture and PCR method, indicating the LAMP-LFB had more advantages in target pathogen detection. CONCLUSIONS: Taken together, LAMP-LFB could be used as an effective diagnostic approach for H. influenzae in the conditions of basic and clinical labs, which would allow clinicians to make better informed decisions regarding patient treatment without delay.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Técnicas Biossensoriais/métodos , Criança , Pré-Escolar , Haemophilus influenzae/genética , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade
5.
Artigo em Chinês | MEDLINE | ID: mdl-35511614

RESUMO

Objective:To assess the presentation of allergic fungal rhinosinusitis(AFRS) in children and the role of long-term comprehensive therapy of endoscopic surgery combined with drug therapy. Methods:The 3 children with AFRS were routinely examined by nasal endoscopy, CT scan, MRI scan and allergen detection before surgery, and mycological and histomathological examination were performed on the secretions in the sinus and the mucosa of the affected sinuses. All the 3 patients underwent endoscopic surgery, preoperative and postoperative treatment with oral and nasal corticosteroid, nasal irrigation, and individualized anti-allergy therapy and immunotherapy. The patients were followed up for 3 to 12 months. Results:All 3 children had nasal polyps and headache, and 2 children had exophthalmos and facial asymmetry. There were typical CT and MRI findings on imaging. Serum total IgE were all elevated, and 2 cases were positive for fungal SIgE. All 3 children underwent endoscopic surgery. Fungal hyphae and spores were found in 1 child, and other fungi tests were positive in another 2 children. Postoperative facial asymmetry was relieved spontaneously, and mucosal swelling and polypoid changes were observed in 2 children. Conclusion:AFRS is a specific type of chronic rhinosinusitis that is not uncommon in children. Early diagnosis, prompt operation, standardized treatment and long-term follow-up are very important in the diagnosis and treatment of AFRS in children.


Assuntos
Micoses , Pólipos Nasais , Rinite Alérgica , Sinusite , Criança , Doença Crônica , Assimetria Facial , Humanos , Micoses/diagnóstico , Micoses/microbiologia , Micoses/terapia , Pólipos Nasais/cirurgia , Rinite Alérgica/cirurgia , Sinusite/diagnóstico
6.
Nanomaterials (Basel) ; 12(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35564310

RESUMO

The morphology and mesoporosity of zeolite are two vital properties to determine its performance in diverse applications involving adsorption and catalysis; while it remains a big challenge for the synthesis and regulation of zeolites with exceptional morphology/porosity only through inorganic-ions-based modification. Herein, by simply optimizing the alkali metal type (K+ or Na+), as well as alkali/water ratio and crystallization temperature, the zeolite ZSM-5 mesocrystals with diverse mesostructures are simply and controllably prepared via fine-tuning the crystallization mechanism in an organotemplate-free, ions-mediated seed-assisted system. Moreover, the impacts of these key parameters on the evolution of seed crystals, the development and assembly behavior of aluminosilicate species and the solution-phase process during zeolite crystallization are investigated by means of directional etching in NH4F or NaOH solutions. Except for the morphology/mesoporosity modulation, their physical and chemical properties, such as particle size, microporosity, Si/Al ratio and acidity, can be well maintained at a similar level. As such, the p/o-xylene adsorption and catalytic performance of o-xylene isomerization are used to exhaustively evaluate the synergistically enhanced catalytic activity and shape selectivity of the obtained products. This work demonstrates the possibility of effectively constructing novel zeolite mesostructures by simply altering parameters on simple ions-controlled crystallization and provides good models to inspect the impacts of mesoporosity or morphology on their catalytic performances.

7.
Bioeng Transl Med ; 7(2): e10267, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35600649

RESUMO

Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)-immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4-butanediol diglycidyl ether (BDDE) would encapsulate di(2-ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP-containing TGA-chitosan gel (CT-D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT-D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT-D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA-immobilized chitosan allows the developed CT-D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.

8.
Mater Today Bio ; 15: 100266, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35517579

RESUMO

Several studies have focused on using cell carriers to solve the problem of mesenchymal stem cell expansion on regenerative medicine. However, the disadvantages of using prolonged enzymatic treatment and low cell harvest efficiency still trouble researchers. In this study, PNIPAAm-immobilized gelatin microspheres (abbreviated as GNMS) were synthesized using a simple power-driven flow-focusing microinjection system. The developed thermosensitive GNMS can allow easier harvesting of cells from the microspheres, requiring only 10 â€‹min of low-temperature treatment and 5 â€‹min of trypsin treatment. The developed GNMS was characterized by Fourier-transform infrared spectroscopy, optical microscopy, and scanning electron microscopy. Further, live/dead staining, F-actin staining, and PrestoBlue cell viability assays were used to evaluate cytotoxicity, cell morphology, cell proliferation, and harvest efficiency. The gene expression of stem cell markers was determined by real-time quantitative PCR (Q-PCR) analysis to investigate the stemness and phenotypic changes in Wharton's jelly-derived mesenchymal stem cells. The results showed that the engineered cell-laden thermosensitive GNMS could significantly increase the cell harvest rate with over 99% cell survival rate and no change in the cell phenotype. Thus, the described strategy GNMS could be the suitable 3D cell carriers in the therapeutic application and opens new avenues for regenerative medicine.

9.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-491301

RESUMO

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

11.
Plant J ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436372

RESUMO

High-affinity phosphate (Pi) transporters (PHTs) PHT1;1 and PHT1;4 are necessary for plant root Pi uptake especially under Pi-deficient conditions, but how their protein stability is modulated remains elusive. Here, we identified a Ttransfer DNA insertion mutant of Sorting Nexin1 (SNX1), which had more Pi content and less anthocyanin accumulation than the wild type under deficient Pi. By contrast, the snx1-2 mutant displayed higher sensitivity to exogenous arsenate in terms of seed germination and root elongation, revealing higher Pi uptake rates. Further study showed that SNX1 could co-localize and interact with PHT1;1 and PHT1;4 in vesicles and at the plasma membrane. Genetic analysis showed that increased Pi content in the snx1-2 mutant under low Pi conditions could be extensively compromised by mutating PHT1;1 in the double mutant snx1-2 pht1;1, revealing that SNX1 is epistatic to PHT1;1. In addition, SNX1 negatively controls PHT1;1 protein stability; therefore, PHT1;1 protein abundance in the plasma membrane was increased in the snx1-2 mutant compared with the wild type under either sufficient or deficient Pi. Together, our study (i) identifies SNX1 as a key modulator of the plant response to low Pi and (ii) unravels its role in the modulation of PHT1;1 protein stability, PHT1;1 accumulation at the plasma membrane, and root Pi uptake.

12.
BMC Ophthalmol ; 22(1): 190, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35468756

RESUMO

PURPOSE: The study aimed to investigate the prevalence of dry eye disease (DED) and relevant risk factors among Chinese high school students during the COVID-19 outbreak. METHODS: A cross-sectional study was conducted from November to December 2020, and 4825 high school students from nine high schools in Shanghai were recruited. All students completed ocular surface disease index (OSDI) and perceived stress scale (PSS) questionnaires and answered other questions designed to ascertain information on the risk factors related to DED. DED was diagnosed when OSDI scores were greater than or equal to 13. The prevalence of symptomatic DED was determined. A T-test, Kruskal-Wallis test, Chi-square test, and logistic regression analysis were used to examine the possible risk factors. RESULTS: The prevalence of symptomatic DED among Chinese high school students was 70.5%. In univariate analysis, higher PSS scores (P<0.001), prolonged video display terminal (VDT) use (P<0.001), wearing contact lenses (P=0.001), poor sleep quality (P<0.001), and being female (P<0.001) were significantly correlated with dry eyes. In multivariate logistic regression analysis, higher PSS scores (P<0.001, OR=1.20), prolonged VDT use (P<0.001, OR=1.07), poor sleep quality (P<0.001, OR=1.84), and being female (P=0.001, OR=1.25) were significant risk factors associated with DED. CONCLUSIONS: Due to the epidemic, most Chinese high school students are in a high-risk environment in which they are more likely to suffer from DED, such as long online courses and heavy stress from school. Relevant preventive measures that may have a positive impact on public health and quality of life for high school students should be brought to the forefront.


Assuntos
COVID-19 , Síndromes do Olho Seco , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Surtos de Doenças , Síndromes do Olho Seco/diagnóstico , Feminino , Humanos , Masculino , Prevalência , Qualidade de Vida , Estudantes , Inquéritos e Questionários
13.
Front Oncol ; 12: 848107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480105

RESUMO

The high radiosensitivity of the intestinal epithelium limits the outcomes of radiotherapy against abdominal malignancies, which results in poor prognosis. Currently, no effective prophylactic or therapeutic strategy is available to mitigate radiation toxicity in the intestine. Our previous study revealed that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) attenuates radiation-induced intestinal injury (RIII). The aim of the present study was to determine the effect of EGCG on the intestinal flora of irradiated mice. EGCG administration reduced radiation-induced intestinal mucosal injury, and significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and Ki67+ crypt cells. In addition, EGCG reversed radiation-induced gut dysbiosis, restored the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria. Our findings provide novel insight into EGCG-mediated remission of RIII, revealing that EGCG could be a potential modulator of gut microbiota to prevent and treat RIII.

14.
World J Surg Oncol ; 20(1): 140, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35490241

RESUMO

BACKGROUND: Pulmonary sclerosing pneumocytoma is a kind of rare benign pulmonary tumor with potential malignancy. The clinical features, risk factors for prognosis, and optimal treatment have not been identified yet. This study aimed to investigate the clinical features and prognosis of pulmonary sclerosing pneumocytoma. METHODS: We retrospectively performed a review of pulmonary sclerosing pneumocytoma patients in West China Hospital from 2009 to 2019. The basic characteristics, treatment regimens, operation detail, postoperative variables, and follow-up time were recorded for each case. Differences in features between patients undergoing lobectomy and segmentectomy were compared. We also performed a case review and summarized reported clinical features in former studies. RESULTS: Altogether 61 pulmonary sclerosing pneumocytoma patients were retrospectively reviewed. Fifty-six patients were female and 5 were male. The patients' median age was 51 (23-73). Seven (11.48%) patients had smoking history. Twenty tumors were located in the right lung [upper lobe (n = 7), middle (n = 2), and lower (n = 11)] and 41 in the left [upper (n = 12) and lower (n = 29)]. The median tumor size was 2 (0.9-7) cm. Thirty-six (59.02%) patients underwent sublobectomy (segmentectomy or wedge resection) whereas 25 (40.98%) underwent lobectomy. All patients recovered uneventfully, and no perioperative mortality was identified. Sublobectomy showed a trend towards reduced chest tube duration and shorter postoperative hospital stays compared with lobectomy. CONCLUSIONS: The findings showed good prognosis of pulmonary sclerosing pneumocytoma and proved its benign characteristics. Sublobectomy showed advanced efficacy regarding chest tube duration and postoperative hospital stay compared with lobectomy.


Assuntos
Neoplasias Pulmonares , Hemangioma Esclerosante Pulmonar , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Hemangioma Esclerosante Pulmonar/patologia , Hemangioma Esclerosante Pulmonar/cirurgia , Estudos Retrospectivos
15.
Science ; 376(6592): 517-521, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35482882

RESUMO

Improving composite battery electrodes requires a delicate control of active materials and electrode formulation. The electrochemically active particles fulfill their role as energy exchange reservoirs through interacting with the surrounding conductive network. We formulate a network evolution model to interpret the regulation and equilibration between electrochemical activity and mechanical damage of these particles. Through statistical analysis of thousands of particles using x-ray phase contrast holotomography in a LiNi0.8Mn0.1Co0.1O2-based cathode, we found that the local network heterogeneity results in asynchronous activities in the early cycles, and subsequently the particle assemblies move toward a synchronous behavior. Our study pinpoints the chemomechanical behavior of individual particles and enables better designs of the conductive network to optimize the utility of all the particles during operation.

16.
Comput Intell Neurosci ; 2022: 6799285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463244

RESUMO

Current epidemiological and experimental studies have indicated the overlapping genetic foundation of epilepsy and depression. However, the detailed pleiotropic genetic etiology and neurobiological pathways have not been well understood, and there are many variants with underestimated effect on the comorbidity of the two diseases. Utilizing genome-wide association study (GWAS) summary statistics of epilepsy (15,212 cases and 29,677 controls) and depression (170,756 cases and 329,443 controls) from large consortia, we assessed the integrated gene-based association with both diseases by Multimarker Analysis of Genomic Annotation (MAGMA) and Fisher's meta-analysis. On the one hand, shared genes with significantly altered transcripts in Gene Expression Omnibus (GEO) data sets were considered as possible pleiotropic genes. On the other hand, the pathway enrichment analysis was conducted based on the gene lists with nominal significance in the gene-based association test of each disease. We identified a total of two pleiotropic genes (CD3G and SLCO3A1) with gene expression analysis validated and interpreted twenty-five common biological process supported with literature mining. This study indicates the potentially shared genes associated with both epilepsy and depression based on gene expression, meta-data analysis, and pathway enrichment strategy along with traditional GWAS and provides insights into the possible intersecting pathways that were not previously reported.


Assuntos
Epilepsia , Estudo de Associação Genômica Ampla , Depressão/genética , Epilepsia/genética , Pleiotropia Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único
17.
Nat Commun ; 13(1): 1902, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393424

RESUMO

All extant core-eudicot plants share a common ancestral genome that has experienced cyclic polyploidizations and (re)diploidizations. Reshuffling of the ancestral core-eudicot genome generates abundant genomic diversity, but the role of this diversity in shaping the hierarchical genome architecture, such as chromatin topology and gene expression, remains poorly understood. Here, we assemble chromosome-level genomes of one diploid and three tetraploid Panax species and conduct in-depth comparative genomic and epigenomic analyses. We show that chromosomal interactions within each duplicated ancestral chromosome largely maintain in extant Panax species, albeit experiencing ca. 100-150 million years of evolution from a shared ancestor. Biased genetic fractionation and epigenetic regulation divergence during polyploidization/(re)diploidization processes generate remarkable biochemical diversity of secondary metabolites in the Panax genus. Our study provides a paleo-polyploidization perspective of how reshuffling of the ancestral core-eudicot genome leads to a highly dynamic genome and to the metabolic diversification of extant eudicot plants.


Assuntos
Genoma de Planta , Panax , Cromatina/genética , Cromossomos , Epigênese Genética , Evolução Molecular , Genoma de Planta/genética , Panax/genética , Filogenia , Poliploidia
18.
Antioxidants (Basel) ; 11(4)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35453412

RESUMO

In Alzheimer's disease (AD), the most common cause of dementia, patients generally forget to take pills or skip medication due to side effects, affecting the treatment efficacy. In this study, we combined a poly(lactic-co-glycolic acid), (PLGA)-poly(ethylene glycol), and (PEG)-PLGA thermo-sensitive hydrogel with curcumin (PGC) to deliver an intramuscular injection that could continuously release curcumin and maintain it at a constant level in blood to prevent AD development or progression. We evaluated the drug release profile and cytotoxicity of PGC and its effects on AD pathology through in vitro and in vivo studies and on cognitive function through an aluminum-chloride-induced AD rat model. In the in vitro study, PGC exhibited a lack of cytotoxicity, excellent anti-inflammatory and antioxidant properties, and microglial modulation. In the Morris water maze test, the PGC injection-administered AD rats presented well-focused searching behavior with the shortest swimming path and longest retention times in the quadrant where the platform was initially located. Furthermore, PGC reduced amyloid-beta aggregation and deposition and significantly increased hippocampal activity. This study demonstrated that intramuscular PGC injection can effectively prevent AD development or progression in rats without inducing toxicity; therefore, this strategy could help overcome the present challenges in AD management in humans.

19.
Gen Physiol Biophys ; 41(2): 159-164, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35416179

RESUMO

Our study aimed to detect the effects of polyphyllin I (PPI) on relieving gestational diabetes mellitus (GDM), and the possible mechanism. A mouse model of GDM was constructed. The effects of PPI on GDM mice were evaluated by detecting blood glucose, insulin level, glucose tolerance test, and insulin tolerance test. The inflammation response in GDM and GDM+PPI group were evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of PPI on the offspring of GDM mice was analyzed. In addition, immunoblot assays were performed to investigate the effects of PPI on the AMPK pathway. We found that PPI improved diabetes-related symptoms and decreased serum inflammatory response in GDM mice. In addition, we also found that PPI reduced the tissue damage of GDM mice. We noticed that PPI alleviated inflammatory injury in GDM mice through targeting AMPK pathway. Our findings showed that PPI has the potential to be explored as the drug for GDM treatment.


Assuntos
Diabetes Gestacional , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/metabolismo , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Diosgenina/análogos & derivados , Feminino , Insulina/metabolismo , Camundongos , Gravidez , Transdução de Sinais
20.
Front Microbiol ; 13: 791802, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418956

RESUMO

Bacterial drug resistance caused by overuse and misuse of antibiotics is common, especially in clinical multispecies infections. It is of great significance to discover novel agents to treat clinical bacterial infections. Studies have demonstrated that autoinducer-2 (AI-2), a signal molecule in quorum sensing (QS), plays an important role in communication among multiple bacterial species and bacterial drug-resistance. Previously, 14 AI-2 inhibited compounds were selected through virtual screening by using the AI-2 receptor protein LuxP as a target. Here, we used Vibrio harveyi BB170 as a reporter strain for the preliminary screening of 14 inhibitors and compound Str7410 had higher AI-2 QS inhibition activity (IC50 = 0.3724 ± 0.1091 µM). Then, co-culture of Pseudomonas aeruginosa PAO1 with Staphylococcus aureus ATCC 25923 was used to evaluate the inhibitory effects of Str7410 on multispecies infection in vitro and in vivo. In vitro, Str7410 significantly inhibited the formation of mixed bacterial biofilms. Meanwhile, the combination of Str7410 with meropenem trihydrate (MEPM) significantly improved the susceptibility of mixed-species-biofilm cells to the antibiotic. In vivo, Str7410 significantly increased the survival rate of wild-type Caenorhabditis elegans N2 co-infected by P. aeruginosa PAO1 and S. aureus ATCC 25923. Real-time quantitative PCR analysis showed that Str7410 reduced virulence factor (pyocyanin and elastase) production and swarming motility of P. aeruginosa PAO1 by downregulating the expression of QS-related genes in strain PAO1 in co-culture with S. aureus ATCC 25923. Compound Str7410 is a candidate agent for treating drug-resistant multispecies infections. The work described here provides a strategy for discovering novel antibacterial drugs.

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