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1.
Neural Regen Res ; 18(3): 587-593, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018182

RESUMO

Mild cognitive impairment (MCI) is a prodrome of Alzheimer's disease pathology. Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods. Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases. This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI. Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls, and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays. Correlation of cognitive performance with the serum exosomal protein level was determined. Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls. We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis. Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients. Exosomal fibulin-1, with an area under the curve value of 0.81, may be a biomarker for an MCI diagnosis. The exosomal protein signature from MCI patients reflected the cell adhesion molecule category. In particular, higher exosomal fibulin-1 levels correlated with lower cognitive performance. Thus, this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI.

2.
Neural Regen Res ; 18(5): 1090-1098, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36254998

RESUMO

Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 µM CHIR99021, and 1 µM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson's disease.

3.
Environ Sci Ecotechnol ; 13: 100207, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36203649

RESUMO

Data-driven approaches that make timely predictions about pollutant concentrations in the effluent of constructed wetlands are essential for improving the treatment performance of constructed wetlands. However, the effect of the meteorological condition and flow changes in a real scenario are generally neglected in water quality prediction. To address this problem, in this study, we propose an approach based on multi-source data fusion that considers the following indicators: water quality indicators, water quantity indicators, and meteorological indicators. In this study, we establish four representative methods to simultaneously predict the concentrations of three representative pollutants in the effluent of a practical large-scale constructed wetland: (1) multiple linear regression; (2) backpropagation neural network (BPNN); (3) genetic algorithm combined with the BPNN to solve the local minima problem; and (4) long short-term memory (LSTM) neural network to consider the influence of past results on the present. The results suggest that the LSTM-predicting model performed considerably better than the other deep neural network-based model or linear method, with a satisfactory R2. Additionally, given the huge fluctuation of different pollutant concentrations in the effluent, we used a moving average method to smooth the original data, which successfully improved the accuracy of traditional neural networks and hybrid neural networks. The results of this study indicate that the hybrid modeling concept that combines intelligent and scientific data preprocessing methods with deep learning algorithms is a feasible approach for forecasting water quality in the effluent of actual engineering.

4.
J Hazard Mater ; 442: 130107, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36303347

RESUMO

Water pollution by toxic organic dyes is one of the most critical health and environmental problems worldwide. By means of molecular dynamics method, the present work aims to evaluate the applicability of montmorillonite (Mt) modified by hexadecyltrimethylammonium cations (HDTMA+) compared to unmodified Na-Mt for the adsorption of cationic methylene blue (MB) dye. The results showed that the adsorption energy of MB on both HDTMA-Mt and Na-Mt absorbent ranged from - 100 to - 250 kJ/mol, indicating the effectiveness of two types of adsorbents in dye water treatment. The highest adsorption energy was found at w = 50% in each adsorbent system. Adsorption mechanisms of MB depend on molecular orientations, which is influenced by the surfactant and water content. The adsorption mechanism of MB is chemisorption dominated by strong electrostatic interaction between CH3 groups of MB and oxygen atoms of Mt surfaces. Besides, physisorption also plays a minor role in MB orientations. It is found that the existence of cationic surfactants can slightly improve the adsorption capacity of MB only at higher water content through enlarging the interlayer space of Mt and reducing mobility of MB. However, there will be a negative impact on the reduction of adsorption sites for dyes especially at low water content. Our results provide a possible application for swelling clay minerals being a promising adsorbent for dyes-surfactants co-existing wastewater treatment.


Assuntos
Bentonita , Poluentes Químicos da Água , Adsorção , Corantes , Tensoativos , Cátions , Azul de Metileno
5.
Zool Res ; 44(1): 78-89, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36349358

RESUMO

Largemouth bass ( Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study, we sequenced 149 largemouth bass fish, including protospecies (imported from the US) and improved breeds (four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection, including several associated with growth (p sst1 and grb10), early development ( klf9, sp4, and sp8), and immune traits ( pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.


Assuntos
Bass , Animais , Bass/genética , Análise de Sequência de DNA/veterinária , Genoma , América do Norte , China
6.
J Environ Manage ; 325(Pt A): 116591, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36419288

RESUMO

Understanding the supply and demand characteristics of ecosystem services (ESs) and their trade-offs is the basis for effective ecosystem management and the improvement of human well-being. However, current management practices based on the trade-offs between the supply and demand for ESs remain limited. This study aimed to integrate ES trade-offs into regional spatial management. With Changzhi, China, as the study area, this study evaluated the supply, demand, and trade-offs of food provision, water conservation, soil retention, and carbon sequestration by linking multi-source data and using spatial analysis tools, including the InVEST model, ArcGIS, and GeoDA. Based on the trade-offs and importance of different ecological functions, we constructed an urban spatial management framework and proposed recommendations for optimization in different management zones. The results showed that (1) the supply and demand for multiple ESs exhibited spatial heterogeneity. Except for water conservation, the supply of other ESs met the demand of the city, but there were still obvious deficits in some regions. (2) In terms of the ES supply, there were trade-offs between food production and other ESs, and synergies existed among water conservation, soil retention, and carbon sequestration. In terms of the ES demand, the four ESs exhibited synergistic relationships. In the cluster analysis, ES supply and demand were divided into four ES bundles, respectively. (3) The spatial mismatch of ESs in the sub-watersheds of the study area was obvious. The ESDR coldspots for the four ESs were primarily located in the urban built-up areas in the central and southern regions of the city. The ESDR hotspots of soil retention and carbon sequestration were mainly distributed in the eastern and northwestern regions of Changzhi, which are less urbanized. There were few ESDR hotspots for food production and water conservation. (4) Based on the regional spatial management framework, Changzhi was divided into ten zones, including extremely important, moderately important, important, supply-demand risk management, soil erosion management, and high food production areas. The results and conclusions of this study provide a basis for spatial planning and ecosystem management.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Conservação dos Recursos Naturais/métodos , Sequestro de Carbono , Solo , Cidades
7.
Curr Probl Cardiol ; 48(1): 101399, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36103941

RESUMO

Cardiac microvascular injury can be a fundamental pathological process that causes high incidence cardiovascular diseases such heart failure, diabetic cardiomyopathy, and hypertension. It is also an independent risk factor for cardiovascular disease. Oxidative stress is a significant pathological process in which the body interferes with the balance of the endogenous antioxidant defense system by producing reactive oxygen species, leading to property changes and dysfunction. It has been demonstrated that oxidative stress is one of the major causes of cardiac microvascular disease. Therefore, additional investigation into the relationship between oxidative stress and cardiac microvascular injury will direct clinical management in the future. In order to give suggestions and support for future in-depth studies, we give a basic overview of the cardiac microvasculature in relation to physiopathology in this review. We also summarize the role of oxidative stress of mitochondrial and non-mitochondrial origin in cardiac microvascular injury and related drug studies.


Assuntos
Cardiomiopatias Diabéticas , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio
8.
Sci Total Environ ; 855: 158911, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36152847

RESUMO

Clostridium sp. LQ25 was cultured in different forms of ferric (ferric citrate and ferric hydroxide) as electron acceptors to investigate growth, ferric reduction, hydrogen production, fermentation products and fermentation process. The growth of the strain LQ25 detected by protein was 82.8 ± 2.1 mg/L and 73.5 ± 1.7 mg/L using ferric citrate and ferric hydroxide as electron acceptors, which was 33.3 % and 18.4 % higher than without ferric, respectively. The accumulation concentration of Fe(II) was 9.0 ± 0.6 mg/L and 5.0 ± 0.2 mg/L when using ferric citrate and ferric hydroxide as electron acceptors, and ferric citrate was 1.8-fold higher than ferric hydroxide, which indicated that the ability of ferric reduction was higher using ferric citrate as electron acceptor. The hydrogen production of strain LQ25 was 238.0 ± 1.0 mmol/mol glucose and 113.0 ± 1.3 mmol/mol glucose under condition of ferric citrate and ferric hydroxide as electron acceptors, which was 2.6 and 1.2-fold higher than without ferric, respectively. The growth and hydrogen production of strain LQ25 was promoted by using ferric as electron acceptor, while the fermentation type of strain did not change and was always butyrate type. The differential expression of the genes of strain LQ25 was significant when using ferric as electron acceptor, mainly in NADH and PFL pathway. This study provided preliminary evidence for hydrogen production by Clostridium sp. LQ25 in the presence of electron acceptor.


Assuntos
Elétrons , Compostos Férricos , Compostos Férricos/metabolismo , Clostridium , Fermentação , Hidrogênio/metabolismo , Glucose/metabolismo
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121886, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137502

RESUMO

Hg2+ in the environment endangers human health, and a convenient monitoring method is needed for the detection of Hg2+. In this study, we constructed a dual colorimetric near-infrared fluorescent probe (E)-2-(3-(3-(1,3-dithian-2-yl)-4-hydroxystyryl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (YF-Hg), based on the malononitrile isophorone. YF-Hg can detect Hg2+ rapidly and sensitively, with fluorescence emission in the near-infrared region (659 nm) with an obvious color change from violet to red in the visible light range. In addition, the low toxicity and large Stokes shift (191 nm) of YF-Hg also suggest that it is a potential tool for live-cell fluorescence imaging.


Assuntos
Colorimetria , Mercúrio , Humanos , Colorimetria/métodos , Corantes Fluorescentes , Células HeLa , Imagem Óptica
10.
J Hazard Mater ; 443(Pt B): 130268, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36327830

RESUMO

Microporous organic networks (MONs) are a booming class of functional materials in elimination of environmental pollutants. However, the limit varieties of MONs still restrict their broad applications. Here we report the synthesis of a novel type of crown ether (CE)-based MONs via the coupling between brominated 18-crown-6 ether and different aromatic alkynyls. The constructed CE-based MONs integrates the good conjugation property of MONs and the inherent host-guest binding sites of CE, allowing the ultrafast and efficient adsorption and removal of a typical environmental priority pollutant 2,4,6-trichlorophenol (2,4,6-TCP). The hydrophobic CE-based MONs can also address the recovery challenge of unstable discrete CE in most organic and inorganic solvents. All CE-based MONs displayed fast adsorption kinetics (< 3 min) and large adsorption capacities (229.1-341.7 mg g-1) for 2,4,6-TCP. The CE-based MONs also gave stable adsorption capacities for 2,4,6-TCP in pH range of 4.0-6.0, NaCl concentration of 0-40 mg L-1, HA concentration of 0-30 mg L-1, or H2O2 ratio of < 5 %. Density functional theory calculation, Fourier transform infrared and X-ray photoelectron spectra evaluation revealed adsorption process involved hydrophobic, π-π and hydrogen bonding interactions. The CE-based MONs also showed favorable reusability and good adsorption for other toxic chlorophenols. This work highlights the potential of CE-based MONs in contaminants elimination.


Assuntos
Clorofenóis , Éteres de Coroa , Poluentes Ambientais , Poluentes Químicos da Água , Clorofenóis/química , Peróxido de Hidrogênio , Adsorção , Poluentes Ambientais/química , Poluentes Químicos da Água/análise
11.
Int J Mol Med ; 51(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36382638

RESUMO

Raf kinase inhibitor protein (RKIP) is an inflammation­inhibiting mediator that is involved in several diseases; however, the potential mechanism of action of RKIP on the inflammatory response induced by influenza A virus (IAV) remains unclear. The present study aimed to investigate whether RKIP regulated the inflammatory response via the ERK/MAPK pathway. The present study detected the expression levels of RKIP and alterations in the inflammatory response in human normal bronchial epithelial BEAS­2B cells, diseased human bronchial epithelial cells and primary human bronchial epithelial cells infected with IAV. Cells were treated with locostatin to inhibit the expression of RKIP. RKIP was overexpressed by lentivirus transduction and the small molecule inhibitor SCH772984 was applied to specifically inhibit activation of the ERK/MAPK pathway. In addition, C57BL/6 mice were infected with IAV to further confirm the role of RKIP in regulation of the inflammatory response via ERK/MAPK in vivo. Western blotting, reverse transcription­quantitative PCR, ELISA, 5­ethynyl­-2'­deoxyuridine assay, immunofluorescence staining, Cell Counting Kit­8, cell cycle assay, hematoxylin and eosin staining, and immunohistochemistry were used to detect all of the changes. Notably, RKIP attenuated the inflammatory response that was triggered by IAV infection in airway epithelial cells, which was characterized by augmented inflammatory cytokines and cell cycle arrest. Furthermore, the ERK/MAPK pathway was revealed to be activated by IAV infection and downregulation of RKIP aggravated the airway inflammatory response. By contrast, overexpression of RKIP effectively ameliorated the airway inflammatory response induced by IAV. These findings demonstrated that RKIP may serve a protective role in airway epithelial cells by combating inflammation via the ERK/MAPK pathway. Collectively, the present findings suggested that RKIP may negatively regulate airway inflammation and thus may constitute a promising therapeutic strategy for airway inflammatory­related diseases that are induced by IAV.


Assuntos
Vírus da Influenza A , Proteína de Ligação a Fosfatidiletanolamina , Camundongos , Animais , Humanos , Proteína de Ligação a Fosfatidiletanolamina/genética , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Camundongos Endogâmicos C57BL , Sistema de Sinalização das MAP Quinases , Inflamação
12.
Phytomedicine ; 108: 154483, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36260972

RESUMO

BACKGROUND: There are many types of neurological diseases with complex etiologies. At present, most clinical drugs can only relieve symptoms but cannot cure these diseases. Radix Polygalae, a famous traditional Chinese medicine from the root of plants of the genus Polygala, has the traditional effect of treating insomnia, forgetfulness, and palpitation and improving intelligence and other symptoms of neurological diseases. Saponins are important bioactive components of plants of the genus Polygala and exhibit neuroprotective effects. PURPOSE: This review aimed to summarize the traditional use of Polygala species and discuss the latest phytochemical, pharmacological, and toxicological findings, mainly with regard to Polygala saponins in the treatment of neurological disorders. METHODS: Literature was searched and collected using databases, including PubMed, Science Direct, CNKI, and Google Scholar. The search terms used included "Polygala", "saponins", "neurological diseases", "Alzheimer's disease", "toxicity", etc., and combinations of these keywords. A total of 1202 papers were retrieved until August 2022, and we included 135 of these papers on traditional uses, phytochemistry, pharmacology, toxicology and other fields. RESULTS: This literature review mainly reports on the traditional use of the Polygala genus and prescriptions containing Radix Polygalae in neurological diseases. Phytochemical studies have shown that plants of the genus Polygala mainly include saponins, flavonoids, oligosaccharide esters, alkaloids, coumarins, lignans, flavonoids, etc. Among them, saponins are the majority. Modern pharmacological studies have shown that Polygala saponins have neuroprotective effects on a variety of neurological diseases. Its mechanism of action involves autophagic degradation of misfolded proteins, anti-inflammatory, anti-apoptotic, antioxidative stress and so on. Toxicological studies have shown that Polygala saponins trigger gastrointestinal toxicity, and honey processing and glycosyl disruption of Polygala saponins can effectively ameliorate its gastrointestinal side effect. CONCLUSION: Polygala saponins are the major bioactive components in plants of the genus Polygala that exhibit therapeutic potential in various neurological diseases. This review provides directions for the future study of Polygala saponins and references for the clinical use of prescriptions containing Radix Polygalae for the treatment of neurological diseases.


Assuntos
Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Polygala , Saponinas , Humanos , Saponinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Flavonoides , Etnofarmacologia
13.
Bioact Mater ; 19: 75-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35441117

RESUMO

Osteoporosis is one of the most disabling consequences of aging, osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths, indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance. Teriparatide is strong bone formation promoter effective in treating osteoporosis, while side effects limit clinical applications. Traditional drug delivery is lack of sensitive and short-term release, finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge. Thus, bioinspired by the natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules, achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand. Herein, biomimetic bone microstructure of mesoporous bioglass, a near-infrared ray triggered switch, thermosensitive liposomes based on a valve, and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration. Teriparatide is pulsatile released from intelligent delivery, not only rejuvenating osteoporotic bone defect, but also presenting strong systemic anti-osteoporosis therapy. This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

14.
Talanta ; 251: 123763, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35932636

RESUMO

Microporous organic networks (MONs) are promising in high performance liquid chromatography (HPLC) with large specific surface area, good hydrophobicity and stability. However, their superhydrophobic structures restrict MONs-based HPLC only in reversed-phase mode. To decrease the hydrophobicity of pristine MONs and to expand their broad application in HPLC, here we described the monomer-mediated fabrication of core-shell MON-2COOH@SiO2 microspheres for reversed-phase liquid chromatography (RPLC)/hydrophilic interaction liquid chromatography (HILIC) mixed-mode chromatography for the first time. The -COOH groups were introduced into MONs' skeleton to improve their hydrophilicity and to provide hydrophilic interaction sites. The MON-2COOH was grafted onto silica via a monomer mediated method to produce monodispersed core-shell microspheres. By adjusting the concentration of reactants, the thickness of MON-2COOH shell was easily manipulated. The packed MON-2COOH@SiO2 column showed high resolution and selectivity for separating both hydrophobic (alkylbenzenes, polycyclic aromatic hydrocarbons, anilines and phenols) and hydrophilic (nucleoside and nucleic bases) probes, highlighting the promise of MONs in mixed-mode HPLC. The MON-2COOH@SiO2 column also achieved good separation to sulfonamides, nonsteroidal anti-inflammatory drugs, flavonoids and phenylurea herbicides, and offered better resolution than commercial C18 and pristine SiO2 column. Multiple retention mechanisms were also found on MON-2COOH@SiO2 packed column, underlining the great potential of MONs in mixed-mode HPLC.


Assuntos
Herbicidas , Hidrocarbonetos Policíclicos Aromáticos , Compostos de Anilina , Anti-Inflamatórios , Cromatografia de Fase Reversa/métodos , Flavonoides , Interações Hidrofóbicas e Hidrofílicas , Microesferas , Nucleosídeos , Fenóis , Dióxido de Silício/química , Sulfonamidas
15.
Cell Biol Int ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316812

RESUMO

Endometrial carcinoma (EC) morbidity and mortality have been increasing in recent years. Otubain 2 (OTUB2) was shown to be upregulated in EC patients, so the aim of this study was to explore the role of OTUB2 in EC. Cell Counting Kit-8 (CCK-8), colony formation, enzyme-linked immunosorbent assay, the wound healing assay, and Transwell invasion assays were used to investigate the specific role of OTUB2 in EC tumorigenesis. Real-time polymerase chain reaction and western blot analysis were used to detect the expression of OTUB2 in EC tissues and cells. OTUB2 is upregulated in EC patients and cell lines and is associated with a poor prognosis. The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells. The silencing of OTUB2 had the opposite effect. In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2. Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC. OTUB2 regulated the proliferation and invasion of EC cells by regulating the PKM2/PI3K/AKT signaling pathway. OTUB2 may serve as a potential prognostic and therapeutic target in EC.

16.
mSystems ; : e0046722, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317888

RESUMO

Establishing transcriptional regulatory networks (TRNs) in bacteria has been limited to well-characterized model strains. Using machine learning methods, we established the transcriptional regulatory networks of six Salmonella enterica serovar Typhimurium strains from their transcriptomes. By decomposing a compendia of RNA sequencing (RNA-seq) data with independent component analysis, we obtained 400 independently modulated sets of genes, called iModulons. We (i) performed pan-genome analysis of the phylogroup structure of S. Typhimurium and analyzed the iModulons against this background, (ii) revealed different genetic signatures in pathogenicity islands that explained phenotypes, (iii) discovered three transport iModulons linked to antibiotic resistance, (iv) described concerted responses to cationic antimicrobial peptides, and (v) uncovered new regulons. Thus, by combining pan-genome and transcriptomic analytics, we revealed variations in TRNs across six strains of serovar Typhimurium. IMPORTANCE Salmonella enterica serovar Typhimurium is a pathogen involved in human nontyphoidal infections. Treating S. Typhimurium infections is difficult due to the species's dynamic adaptation to its environment, which is dictated by a complex transcriptional regulatory network (TRN) that is different across strains. In this study, we describe the use of independent component analysis to characterize the differential TRNs across the S. Typhimurium pan-genome using a compendium of high-quality RNA-seq data. This approach provided unprecedented insights into the differences between regulation of key cellular functions and pathogenicity in the different strains. The study provides an impetus to initiate a large-scale effort to reveal the TRN differences between the major phylogroups of the pathogenic bacteria, which could fundamentally impact personalizing treatments of bacterial pathogens.

17.
Int Immunopharmacol ; 113(Pt A): 109263, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334370

RESUMO

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.

18.
Sci Rep ; 12(1): 18749, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335196

RESUMO

There is a high rate of recurrent hypertriglyceridemic acute pancreatitis (HTG-RAP) and risk of developing into chronic pancreatitis among recurrent hypertriglyceridemic acute pancreatitis. The key to avoiding recurrence is home-based self-management. However, self-management has proven to be difficult. Exploring experiences and perceptions of home-based self-management among patients with HTG-RAP could inform intervention development and policy making in primary care. To explore experiences and perceptions of home-based self-management among patients with HTG-RAP. This is primarily a qualitative study involving patients from eastern China. The study was designed using semi-structured interviews combined with open interviews among individuals and focus groups. Interviews with patients (n = 25) and relatives (n = 2) were conducted from October to December, 2021. Data were analyzed using the thematic analysis approach. Five themes were identified: (1) pity, (2) sense of uncertainty, (3) contradiction, (4) the way to cope, and (5) benefits. The themes constituted a continuous process where a final coping strategy was confirmed. Patients expressed sorrow, struggle, pity, adaptation, and benefits. The disease still bothered them without attack, both mentally and physically. These key points deserve considerable attention to improve the quality of life of patients and lifestyle modification. Patients with pancreatitis were more likely to manage the disease but under a tough process, and during the struggle, they experienced a continuous and contradictory period. Ultimately, the final condition was reached.


Assuntos
Pancreatite Crônica , Qualidade de Vida , Humanos , Doença Aguda , Pesquisa Qualitativa , Pancreatite Crônica/terapia
19.
Front Nutr ; 9: 999489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337642

RESUMO

Obesity and vitamin D deficiency are both considered risk factors for mortality, but the potential additive effects of vitamin D status and obesity on mortality has not been well-studied. We aimed to examine the possible additive effects of obesity and vitamin D status on all-cause and cause-specific mortality. The data from the NHANES III (1988-1994) and NHANES 2001-2014 surveys were used, and multivariate Cox regression models were performed to assess the additive effects of vitamin D status and overweight/obesity/abdominal obesity on the all-cause, cardiovascular and cancer mortality, by stratifying Cox Hazard Ratios (HRs) across different categories of vitamin D status and body mass index (BMI) and waist circumference (WC) categories. The models were adjusted for age, race/ethnicity, gender, educational level, family income to poverty ratio, leisure-time physical activity, smoking, and drinking. Across all BMI/WC categories, there was an additive effect of the vitamin D both insufficiency and deficiency on all mortality rates, with deficiency having much stronger effect than insufficiency. Interestingly, the effect of vitamin D deficiency overcame the effect of obesity on all mortality rates. The highest HRs for overall and cardiovascular mortality were observed among vitamin D deficient obese/abdominally obese subjects, while for cancer mortality among vitamin D deficient normal weight/non-abdominally obese subjects. In stratified analyses, regarding all-cause mortality, there was an additive effect of the vitamin D both insufficiency and deficiency in all BMI/WC categories. Regarding cardiovascular mortality, there was an additive effect of vitamin D deficiency in all BMI/WC categories, but the additive effect of vitamin D insufficiency reached significance only in normal weight subjects. Regarding cancer mortality, the effect did not reach significance among obese subjects for vitamin D deficiency, while for insufficiency, significance was reached only among non-abdominally obese subjects. Interestingly, vitamin D surplus was associated with increased risk for cancer mortality in obese subjects, but there was an inadequate number of subjects in this category to make proper judgment. In conclusion, vitamin D insufficiency and deficiency gradually increase risk for mortality across all BMI/WC categories. In our analyses, vitamin D deficiency overcame the effect of obesity on mortality rates.

20.
Front Genet ; 13: 1045244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338963

RESUMO

Background: Infantile hemangiomas (IH) and venous malformations (VM) are the most common types of vascular abnormalities that seriously affect the health of children. Although there is evidence that these two diseases share some common genetic changes, the underlying mechanisms need to be further studied. Methods: The microarray datasets of IH (GSE127487) and VM (GSE7190) were downloaded from GEO database. Extensive bioinformatics methods were used to investigate the common differentially expressed genes (DEGs) of IH and VM, and to estimate their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Trough the constructing of protein-protein interaction (PPI) network, gene models and hub genes were obtained by using Cytoscape and STRING. Finally, we analyzed the co-expression and the TF-mRNA-microRNA regulatory network of hub genes. Results: A total of 144 common DEGs were identified between IH and VM. Functional analysis indicated their important role in cell growth, regulation of vasculature development and regulation of angiogenesis. Five hub genes (CTNNB1, IL6, CD34, IGF2, MAPK11) and two microRNA (has-miR-141-3p, has-miR-150-5p) were significantly differentially expressed between IH and normal control (p < 0.05). Conclusion: In conclusion, our study investigated the common DEGs and molecular mechanism in IH and VM. Identified hub genes and signaling pathways can regulate both diseases simultaneously. This study provides insight into the crosstalk of IH and VM and obtains several biomarkers relevant to the diagnosis and pathophysiology of vascular abnormalities.

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