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1.
Eur J Med Chem ; 243: 114729, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36084535

RESUMO

Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17-1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE < 20 nM, eeAChE > 10 µM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Aß1-42 induced damage. It also demonstrated that 17c and 19c were able to restore cognitive impairment in vivo test. These data suggest that 17c and 19c represent promising candidate for follow-up in the drug-discovery process against AD.

2.
Acta Pharmacol Sin ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127507

RESUMO

Aversive emotion of opioid withdrawal generates motivational state leading to compulsive drug seeking and taking. Kappa opioid receptor (KOR) and its endogenous ligand dynorphin have been shown to participate in the regulation of aversive emotion. In the present study, we investigated the role of dynorphin/KOR system in the aversive emotion following opioid withdrawal in acute morphine-dependent mice. We found that blockade of KORs before pairing by intracerebroventricular injection of KOR antagonist norBNI (20, 40 µg) attenuated the development of morphine withdrawal-induced conditioned place aversion (CPA) behavior. We further found that morphine withdrawal increased dynorphin A expression in the dorsal hippocampus, but not in the amygdala, prefrontal cortex, nucleus accumbens, and thalamus. Microinjection of norBNI (20 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-induced CPA behavior. We further found that p38 MAPK was significantly activated in the dorsal hippocampus after morphine withdrawal, and the activation of p38 MAPK was blocked by pretreatment with norBNI. Accordingly, microinjection of p38 MAPK inhibitor SB203580 (5 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-produced CPA behavior. This study demonstrates that upregulation of dynorphin/KOR system in the dorsal hippocampus plays a critical role in the formation of aversive emotion associated with morphine withdrawal, suggesting that KOR antagonists may have therapeutic value for the treatment of opioid withdrawal-induced mood-related disorders.

3.
Front Neurol ; 13: 931551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119704

RESUMO

Objective: Hemifacial spasm (HFS) is a common neurological disorder of the brain, which is difficult to treat. Most patients are distracted by it and are unable to work or study normally, which seriously affects their physical and mental health. However, there are a few bibliometric studies on it. This paper searched the articles on HFS using a bibliometric approach. Method: Articles about HFS were retrieved from the Web of Science (WoS) Core Collection database. We employed the Visualization of Similarities (VOS)viewer to analyze these publications. Results: A total of 645 reviews or articles in English were retrieved from WoS. In this study, we found that the number of publications showed a rising trend and China is the most active in searching the treatment of HFS. About keywords, neurosciences and neurology was searched (422 times) keyword, followed by hemifacial spasm (420 times) and surgery (320 times). By assessing the organizations, Shanghai Jiao Tong University published the most papers (8.68%), followed by Sungkyunkwan University (3.26%) and Baylor College Medicine (2.64%). A total of 247 journals have delivered publications on the treatment of HFS, World Neurosurgery (44 papers) published the largest number of articles. Conclusion: The annual publications have increased with a fluctuating tendency. More researchers were taking an interest in HFS. This study helped us find out the hotspot and trend in research about facial spasm treatment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36124413

RESUMO

INTRODUCTION: Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. MATERIAL AND METHODS: PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin, and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. RESULTS: PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. CONCLUSIONS: This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.

5.
J Exp Med ; 219(11)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36048018

RESUMO

Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s and ILC3-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3 homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-γ production, dysbiosis, aberrant T cell immune responses, and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by the removal of adaptive immunity, interferon-γ blockade, or antibiotic treatment. Mechanistically, BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility, and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways, which in turn directly promotes the transition of precursor ILC3s to MHCII+ ILC3s. Collectively, our findings reveal that BATF is a key transcription factor for maintaining ILC3 stability and coordinating ILC3-mediated control of intestinal homeostasis.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Imunidade Inata , Linfócitos , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Cromatina/metabolismo , Homeostase , Interferon gama/metabolismo , Mucosa Intestinal , Camundongos
6.
Psychol Res Behav Manag ; 15: 2501-2511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36104998

RESUMO

Background: Depressive symptoms are prevalent in persons with type 2 diabetes mellitus and related with poor disease outcomes. Both general self-efficacy and coping style are associated with depressive symptoms. A model about proactive coping indicates that coping style plays a mediation role between general self-efficacy and depressive symptoms. But, empirical evidence is missing about this potential mediation relationship which may be a barrier of taking precise strategies for relieving depressive symptoms. Objective: This study aims to investigate the prevalence of elevated depressive symptoms in persons with type 2 diabetes mellitus and explore whether coping style preference mediates the association between general self-efficacy and depressive symptoms. Methods: This was a secondary data analysis of a cross-sectional survey (June-July 2017) among 721 persons with type 2 diabetes mellitus (45.4% male and 54.6% female) aged from 22 to 96 years old. Data on general self-efficacy, coping style preference and depressive symptoms were collected using validated questionnaires in hospital setting. The mediation model was tested using the bootstrapping (K=5000) in the MPlus program version 7.4. The results were reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: The prevalence of elevated depressive symptoms was 58% (n = 418) among persons with type 2 diabetes mellitus at hospital setting. A higher level of general self-efficacy was related to less depressive symptoms via positive coping preference (p < 0.01). Discussion: About two-thirds of persons with type 2 diabetes mellitus experienced elevated depressive symptoms during hospitalization. The intervention elements, including strengthening general self-efficacy and promoting positive coping, are promising to decrease their depressive symptoms.

7.
Front Cell Dev Biol ; 10: 973073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111345

RESUMO

The most common intraocular malignancy in adults remains uveal melanoma (UVM), and those with metastatic disease have a poor outlook. Proliferation, angiogenesis, and metastasis of tumor cells can be triggered by cuproptosis, affecting the survival of cancer patients. Nonetheless, cuproptosis-related genes (CRGs) have not been identified in UVM. In this study, we analyzed 10 CRGs in 80 patients with UVM in the Cancer Genome Atlas (TCGA) database regarding the alterations of the genes including copy number variation and methylation. We further constructed a prognostic gene model using these CRGs and built the risk score formula. Univariate and multivariate Cox regression was applied to validate the risk score as an independent prognostic factor. The prognostic model was validated using 63 UVM samples from the GSE22138 cohort, an independent validation data set. Based on the risk scores for 80 patients with UVM from TCGA, we categorized the patients into high- and low-risk groups. Differentially expressed genes (DEGs) between groups were enriched in allograft rejection, hypoxia, glycolysis, TNFα signaling via NF-κB, and interferon-γ responses via Gene set enrichment analysis (GSEA). CD8 T cells and exhausted T cells were notably enriched in the high-risk group. In conclusion, the alteration of CRGs is related to patients with UVM, and the constructed CRG-related model may be helpful to predict the prognosis of such patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36113845

RESUMO

Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.

9.
Langmuir ; 38(36): 10934-10942, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36047674

RESUMO

Four kinds of hydrophobic magnetic deep eutectic solvents (HMDESs) were prepared and applied to RNA extraction. Based on the HMDESs, a mechanical shaking-assisted liquid-liquid extraction (MSLLE) was developed for the extraction of RNA. Factors that influence the extraction, including the extraction time, temperature, volume of HMDES, buffer types, and pH, were evaluated. After the optimization of all conditions, the RNA extraction efficiency was 82.31 ± 0.02%. RNA can be extracted from complex samples and medicinal yeast by the method proposed in this work and can be recovered from the HMDESs after being extracted.


Assuntos
Solventes Eutéticos Profundos , RNA , Extração Líquido-Líquido , Fenômenos Magnéticos , Solventes/química
10.
Environ Res ; : 114179, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36100103

RESUMO

This work studies the interaction of organic nanoparticles (ON) with various dyes in aqueous solution, to elucidate the role of ON on transport and fate of dyes in the environment, and on dyes removal from wastewater. Studied dyes are Acid Red 66 (AR66), Methylene Blue (MB), Reactive Black 5 (RB5), and Reactive Violet 5 (RV5). ON are extracted from organic matter of anthropogenic origin through resuspension of its colloidal fraction, and successive filtration and dialysis of the obtained suspension. Mechanisms of interaction are investigated initially through three-dimensional excitation emission matrix (3DEEM) analysis. Obtained data indicate that dynamic interactions occur strongly between dye molecules and ON aggregates. 3DEEM spectra of mixed samples containing ON together with one of the tested dyes, present a shape similar to the one of ON alone, but each of them is characterized by specific differences in terms of peaks quenching and shift. The analysis of these singularities suggests that dye molecules are bound to the functional groups of ON through H-bonds, according to the following steps: i) dyes reach the surface of ON aggregates; ii) the molecules pass through the hydrophilic surface of ON aggregates, and reach their hydrophobic core; iii) the dyes are sequestrated into the hydrophobic core of ON aggregates. Nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopies analysis confirm the formation of supramolecular aggregates with stable micellar hydrophobic structure, mainly consisting of aliphatic fractions of ON, which explain the disappearance of aromatic groups signals from dyes.

11.
Phys Rev E ; 106(2-1): 024112, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36109990

RESUMO

Brownian yet non-Gaussian processes have recently been observed in numerous biological systems, and corresponding theories have been constructed based on random diffusivity models. Considering the particularity of random diffusivity, this paper studies the effect of an external force acting on two kinds of random diffusivity models whose difference is embodied in whether the fluctuation-dissipation theorem is valid. Based on the two random diffusivity models, we derive the Fokker-Planck equations with an arbitrary external force, and we analyze various observables in the case with a constant force, including the Einstein relation, the moments, the kurtosis, and the asymptotic behaviors of the probability density function of particle displacement at different timescales. Both the theoretical results and numerical simulations of these observables show a significant difference between the two kinds of random diffusivity models, which implies the important role of the fluctuation-dissipation theorem in random diffusivity systems.

12.
Curr Med Chem ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111760

RESUMO

Tyrosinase is a bifunctional polyphenol oxidase (PPO), catalyzing two oxidative reactions: monophenols to o-quinones (monophenolase activity) and o-diphenols to o-quinones (diphenolase activity). As tyrosinase is the rate-limiting enzyme for the melanogenesis process, it is an attractive target for melanogenesis inhibition. Aiming at skin whitening, anticancer, Parkinson's disease (PD) treatment, antibacterial, fruit and vegetable preservation and other anti-pigmentation effect, medicinal chemists have exploited diverse tyrosinase inhibitors through various approaches. In addition to discovering inhibitors with novel scaffold, good activity and high safety, researchers also focused on developing strategies for synergistic effects of multiple inhibitors and simultaneously regulating multiple targets to treat cancer or neurodegenerative diseases. This review focused on multiple natural and synthetic tyrosinase inhibitors which could contribute to preventing fruit and vegetable browning, skin whitening, antibacterial, anticancer, Parkinson's Disease etc.

13.
Am J Obstet Gynecol MFM ; : 100752, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115572

RESUMO

BACKGROUND: Although live-birth rates were comparable between programmed and natural frozen-thawed embryo transfer (FET) cycles, recent data showed that pregnancies following programmed cycle were associated with an increased risk of adverse perinatal outcomes such as hypertensive disorders of pregnancy. Such a difference might be attributed to selection bias due to the fact that patients with ovulation disorders were more likely to receive programmed endometrial preparation protocol than natural cycle (NC). OBJECTIVE: To analyze whether programmed endometrial preparation protocol is associated with an increased risk of adverse perinatal outcomes than natural cycle (NC) during frozen embryo transfer (FET) in ovulatory women. STUDY DESIGN: This regional multicenter retrospective cohort study was conducted in five reproductive medical centers in southeast of China. Patients with regular cycles (21-35 days), who underwent either programmed or NC blastocyst FET and delivered singleton live birth babies after 28 weeks of gestation between the year of 2016 and 2019 were analyzed. Each patient only contributed one cycle per cohort. Patients' FET treatment cycles were linked to their obstetrical medication record, and a comprehensive chart review was conducted to compare the maternal and neonatal outcomes between NC-FET and programmed-FET cycles. Crude and adjusted odds ratio with 95% confidence interval were calculated and adjustment was made for relevant confounders. RESULTS: Study samples included 499 NC-FET cases and 900 programmed-FET cases. Pregnancies after programmed cycle were associated with increased odds of hypertensive disorders of pregnancy (HDP) [adjusted odds ratio (aOR) 2.71, 95% confidence interval (CI), 1.59-4.91] and preeclampsia (aOR 2.71, 95%CI 1.17-6.23) in comparison to pregnancies after NC-FET. No significant differences were detected regarding other adverse perinatal outcomes between two endometrial protocols. In subgroup analysis, both the subgroups of hormone replacement therapy (HRT) and HRT with gonadotrophin releasing hormone analogue (GnRHa) pretreatment had increased odds of developing HDP than the NC group. The risk of developing preeclampsia was higher in the GnRHa-HRT subgroup than the other two groups (aOR 4.99, 95%CI 1.94-12.82). CONCLUSION: Pregnancies following programmed FET are associated with higher risks of HDP in ovulatory women. The GnRHa-HRT cycle leads to the highest risk of preeclampsia among the three protocols.

14.
Europace ; 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056883

RESUMO

AIMS: Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. METHODS AND RESULTS: A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, ΔF/F0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, ΔF/F0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 µM], ranolazine (an INa-Late inhibitor, 10 µM), and N-(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. CONCLUSION: Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment.

15.
J Environ Manage ; 322: 116123, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36063698

RESUMO

Marine oil spills emanating from wells, pipelines, freighters, tankers, and storage facilities draw public attention and necessitate quick and environmentally friendly response measures. It is sometimes feasible to contain the oil with booms and collect it with skimmers or burn it, but this is impracticable in many circumstances, and all that can be done without causing further environmental damage is adopting natural attenuation, particularly through microbial biodegradation. Biodegradation can be aided by carefully supplying biologically accessible nitrogen and phosphorus to alleviate some of the microbial growth constraints at the shoreline. This review discussed the characteristics of oil spills, origin, ecotoxicology, health impact of marine oils spills, and responses, including the variety of remedies and responses to oil spills using biological techniques. The different bioremediation and bio-dispersant treatment technologies are then described, with a focus on the use of green surfactants and their advances, benefits/drawbacks. These technologies were thoroughly explained, with a timeline of research and recent studies. Finally, the hurdles that persist as a result of spills are explored, as well as the measures that must be taken and the potential for the development of existing treatment technologies, all of which must be linked to the application of integrated procedures.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36082671

RESUMO

Coordination-driven crosslinking networks with reversible and dynamic characteristics are gaining increasing interest in diverse application fields. Herein, we use a coordination crosslinking approach using metal-organic polyhedra (MOPs) as high-connectivity building blocks to post-assemble a class of coordination hypercrosslinked MOP (CHMOP) polymers. The introduction of 12-connected MOP nodes to the polymeric networks is critical to producing membranes that overcome the trade-off between mechanical properties and dynamic self-healing, and meanwhile possess multifunctionalities including shape memory, solution processability, and 3D printing. The CHMOPs can also be used for anticorrosion coating and achieve function couplings, e.g., shape memory-assisted self-healing (SMASH), which have not been achieved in the MOP-based hybrid materials yet. This work not only offers a feasible strategy to construct new multifunctional materials but also greatly expands the application scopes of MOPs.

17.
Cells ; 11(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36139490

RESUMO

Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF.

18.
Biosensors (Basel) ; 12(9)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36140132

RESUMO

A sensitive and selective electrochemical deoxyribonucleic acid (DNA) biosensor was developed for the determination of a osteosarcoma-related survivin gene by using celestine blue (CB) as a label-free hybridization indicator. The proposed strategy adopted a facile and low-cost working electrode with no need for other substances for electrode or DNA functionalization. The interaction mode between CB and DNA was studied by electrochemical and spectroscopic approaches, illustrating that the possible mode was intercalation with a binding number of 2 and a binding constant ß of 1012.87. Moreover, the label-free electrochemical DNA biosensor exhibited a good linear relationship toward the target gene in a range from 1.00 nM to 50.00 nM with a detection limit as low as 0.046 nM using 3σ estimating system. This facile and low-cost electrochemical method realized the rapid detection and accurate quantification of the target sequence in complicated serum samples, endowing its promising potential in the diagnosis and monitoring of genetic diseases.

19.
Pathogens ; 11(9)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36145400

RESUMO

Rapidly growing mycobacteria (RGM) has gained increasing clinical importance, and treatment is challenging due to diverse drug resistance. The minimum inhibitory concentrations (MIC) of 13 antimicrobial agents using modified broth microdilution and E-test were determined for 32 clinical isolates of RGM, including Mycobacterium abscessus (22 isolates) and Mycobacterium fortuitum (10 isolates). Our results showed high rates of resistance to available antimicrobial agents. Amikacin remained highly susceptible (87.5%). Clarithromycin was active against the isolates of M. abscessus (95.5%), and M. fortuitum (50%), but 36.4% and 20% had inducible macrolide resistance, respectively. Rates of susceptibility to tigecycline were 68.2-70%, and linezolid 45.5-50%, respectively. The quinolones (ciprofloxacin and moxifloxacin) showed better in vitro activity against M. fortuitum isolates (50% susceptibility) than the M. abscessus isolates (31.8% susceptibility). The susceptibilities to other conventional anti-mycobacterial agents were poor. The MICs of E-test were higher than broth microdilution and may result in reports of false resistance. In conclusion, the implementation of the modified broth microdilution plates into the routine clinical laboratory workflow to provide antimicrobial susceptibility early, allows for the timely selection of appropriate treatment of RGM infections to improve outcome.

20.
Plants (Basel) ; 11(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36145840

RESUMO

The plant glutamate receptor-like gene (GLR) plays a vital role in development, signaling pathways, and in its response to environmental stress. However, the GLR gene family has not been comprehensively and systematically studied in sugarcane. In this work, 43 GLR genes, including 34 in Saccharum spontaneum and 9 in the Saccharum hybrid cultivar R570, were identified and characterized, which could be divided into three clades (clade I, II, and III). They had different evolutionary mechanisms, the former was mainly on the WGD/segmental duplication, while the latter mainly on the proximal duplication. Those sugarcane GLR proteins in the same clade had a similar gene structure and motif distribution. For example, 79% of the sugarcane GLR proteins contained all the motifs, which proved the evolutionary stability of the sugarcane GLR gene family. The diverse cis-acting regulatory elements indicated that the sugarcane GLRs may play a role in the growth and development, or under the phytohormonal, biotic, and abiotic stresses. In addition, GO and KEGG analyses predicted their transmembrane transport function. Based on the transcriptome data, the expression of the clade III genes was significantly higher than that of the clade I and clade II. Furthermore, qRT-PCR analysis demonstrated that the expression of the SsGLRs was induced by salicylic acid (SA) treatment, methyl jasmonic acid (MeJA) treatment, and abscisic acid (ABA) treatment, suggesting their involvement in the hormone synthesis and signaling pathway. Taken together, the present study should provide useful information on comparative genomics to improve our understanding of the GLR genes and facilitate further research on their functions.

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