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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35557101

RESUMO

BACKGROUND: The early detection of colorectal cancer (CRC), especially at precancerous adenoma stage, significantly reduces its incidence. Gut microbiome has become a promising non-invasive tool for CRC screening, whereas the potential of microbial multidimensional signatures remains poorly understood. Here we performed a cross-cohort analysis to evaluate the capability of microbial multidimensional biomarkers for adenoma detection. DESIGN: Whole metagenome sequencing data of four public datasets including 183 adenoma patients and 439 healthy controls were reprocessed consistently to obtain taxonomic-, functional- and single-nucleotide variants (SNVs)-profiling. With MMUPHin, differential multidimensional signatures were identified after adjusting confounders, based on which random forest (RF) models were constructed and then optimized by recursive feature elimination. Finally, internal validation and external validation with in-house dataset (10 controls and 6 adenomas) and five resampled datasets were conducted to further assess the robustness of the best biomarker panel. RESULTS: The integrated analysis identified 103 multi-kingdom differential species between adenoma and control group, of which 15 optimal species were selected to construct a RF model achieving an AUC of 0.75. Meanwhile, the model constructed with 31 optimal biomarkers out of 386 differential KO genes reached an AUC of 0.74. Notably, the diagnostic model with 75 SNVs from 10 species showed superior accuracy (AUC = 0.85) with high specificity to adenoma. Co-abundance analysis revealed intensive bacterial-fungal associations in line with functional abnormalities related to microbial quorum sensing, purine and butanoate metabolism. CONCLUSION: Microbial SNV biomarkers outperform other biomarkers and display high specificity to adenoma, which may serve as a novel non-invasive tool for early detection of CRC. Furthermore, multidimensional signatures provide potential therapeutic targets for adenoma.

2.
Nano Lett ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533211

RESUMO

Picturing the atomic migration pathways of catalysts in a reactive atmosphere is of central significance for uncovering the underlying catalytic mechanisms and directing the design of high-performance catalysts. Here, we describe a reduction-controlled atomic migration pathway that converts nanoparticles to single atom alloys (SAAs), which has remained synthetically challenging in prior attempts due to the elusive mechanism. We achieved this by thermally treating the noble-metal nanoparticles M (M = Ru, Rh, Pd, Ag, Ir, Pt, and Au) on metal oxide (CuO) supports with H2/Ar. Atomic-level characterization revealed such conversion as the synergistic consequence of noble metal-promoted H2 dissociation and concomitant CuO reduction. The observed atomic migration pathway offers an understanding of the dynamic mechanisms study of nanomaterials formation and catalyst design.

3.
Polymers (Basel) ; 14(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35567051

RESUMO

The development and treatment of some diseases, such as large-area cerebral infarction, cerebral hemorrhage, brain tumor, and craniocerebral trauma, which may involve the injury of the dura mater, elicit the need to repair this membrane by dural grafts. However, common dural grafts tend to result in dural adhesions and scar tissue and have no further neuroprotective effects. In order to reduce or avoid the complications of dural repair, we used PLGA, tetramethylpyrazine, and chitosan as raw materials to prepare a nanofibrous dura mater (NDM) with excellent biocompatibility and adequate mechanical characteristics, which can play a neuroprotective role and have an antifibrotic effect. We fabricated PLGA NDM by electrospinning, and then chitosan was grafted on the nanofibrous dura mater by the EDC-NHS cross-linking method to obtain PLGA/CS NDM. Then, we also prepared PLGA/TMP/CS NDM by coaxial electrospinning. Our study shows that the PLGA/TMP/CS NDM can inhibit the excessive proliferation of fibroblasts, as well as provide a sustained protective effect on the SH-SY5Y cells treated with oxygen-glucose deprivation/reperfusion (OGD/R). In conclusion, our study may provide a new alternative to dural grafts in undesirable cases of dural injuries.

4.
Ann Transl Med ; 10(8): 483, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571424

RESUMO

Background: The aim of the present study was to investigate the effect of acellular nerve scaffold (ANS) containing human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on nerve repair and regeneration in rats with sciatic nerve defect. Methods: Sciatic nerve trunks were removed from 6 female Sprague-Dawley (SD) rats, and ANS was prepared by lyophilization + enzymatic method and divided into A, B, C, D and E groups according to different treatment times. hUC-MSCs were isolated from the collected umbilical cords and cultured, and then ANS-hUC-MSCs complexes were made. The other 24 adult female SD rats were randomly divided into the control, autograft, ANS, and ANS-hUC-MSCs groups, and a rat model of sciatic nerve defect was established. Hematoxylin-eosin (HE) staining, Luxol fast blue (LFB) staining, Masson staining, and scanning electron microscopy were used to observe the morphology and tissue structure of ANS. The performance of ANS was evaluated by mechanical detection, and hydroxyproline (HYP) content was evaluated using a biochemical kit. Flow cytometry was adopted to detect the levels of hUC-MSCs surface antigens CD29, CD44, and CD34, as well as electrophysiological detection and muscle wet weight recovery rate for measuring rat muscle performance. Results: ANS was prepared according to group A method and had good mechanical properties, with less residues of cells and myelin, and higher HYP content, indicating that this scaffold had the best performance. ANS-hUC-MSCs significantly reduced myelin injury in the sciatic nerve, and increased axonal regeneration, effectively improving sciatic nerve injury in rats. In addition, ANS-hUC-MSCs significantly increased compound muscle action potential (CMAP), nerve conduction velocity (NCV), and muscle wet weight, and reduced muscle atrophy. Conclusions: ANS containing hUC-MSCs can promote nerve repair and regeneration in rats with sciatic nerve defects.

5.
Ying Yong Sheng Tai Xue Bao ; 33(3): 837-843, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35524539

RESUMO

The species distribution models (SDMs) simulate and predict the potential distribution of species in geographical space by quantifying the relationships between species distribution and environmental variables, and extrapolating these relationships to unknown landscape units, which makes them important tools in ecology, biogeo-graphy, and conservation biology. Current SDMs mainly take abiotic factors as prediction variables, whereas biotic factors, especially species interactions, are often ignored due to the difficulties in data quantification and modeling. Incorporating species interactions into SDMs is considered as the main challenge of SDMs. We reviewed the influence of species interactions on species distribution simulations, clarified the necessity of incorporating species interactions into SDMs, summarized four main ways to incorporate species interactions into SDMs, analyzed their strengths and limitations, and discussed the future development direction of incorporating species interactions into SDMs. The study showed that incorporating species interaction into SDMs was based on the premise that the spatial scale of species distribution simulation was consistent with that of species interactions, and that the training data should be collected from large environmental heterogeneous space to ensure the diversity of species interactions in heterogeneous habitats. In order to eliminate the influence of multicollinearity on the prediction of SDMs, all abiotic and biotic factors should be fully considered and accurately quantified. Modeling the complex population/community dynamics would be an important development direction of incorporating species interactions into SDMs.


Assuntos
Ecologia , Ecossistema , Previsões
6.
Artigo em Inglês | MEDLINE | ID: mdl-35560211

RESUMO

Marital quality may decrease during the early years of marriage. Establishing models predicting individualized marital quality may help develop timely and effective interventions to maintain or improve marital quality. Given that marital interactions have an important impact on marital wellbeing cross-sectionally and prospectively, neural responses during marital interactions may provide insight into neural bases underlying marital wellbeing. The current study applies connectome-based predictive modeling, a recently developed machine-learning approach, to fMRI data from both partners of 25 early-stage Chinese couples to examine whether an individual's unique pattern of brain functional connectivity (FC) when responding to spousal interactive behaviors can reliably predict their own and their partners' marital quality after 13 months. Results revealed that husbands' FC involving multiple large networks, when responding to their spousal interactive behaviors, significantly predicted their own and their wives' marital quality, and this predictability showed gender specificity. Brain connectivity patterns responding to general emotional stimuli and during resting state were not significantly predictive. This study demonstrates husbands' differences in large-scale neural networks during marital interactions may contribute to their variability in marital quality, and highlights gender-related differences. Findings lay a foundation for identifying reliable neuroimaging biomarkers for developing interventions for marital quality early in marriages.

7.
Gut Microbes ; 14(1): 2070391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491895

RESUMO

Hyperuricemia is the second most prevalent metabolic disease to human health after diabetes. Only a few clinical drugs are available, and most of them have serious side effects. The human body does not have urate oxidase, and uric acid is secreted via the kidney or the intestine. Reduction through kidney secretion is often the cause of hyperuricemia. We hypothesized that the intestine secretion could be enhanced when a recombinant urate-degrading bacterium was introduced into the gut. We engineered an Escherichia coli Nissle 1917 strain with a plasmid containing a gene cassette that encoded two proteins PucL and PucM for urate metabolism from Bacillus subtilis, the urate importer YgfU and catalase KatG from E. coli, and the bacterial hemoglobin Vhb from Vitreoscilla sp. The recombinant E. coli strain effectively degraded uric acid under hypoxic conditions. A new method to induce hyperuricemia in mice was developed by intravenously injecting uric acid. The engineered Escherichia coli strain significantly lowered the serum uric acid when introduced into the gut or directly injected into the blood vessel. The results support the use of urate-degrading bacteria in the gut to treat hyperuricemia. Direct injecting bacteria into blood vessels to treat metabolic diseases is proof of concept, and it has been tried to treat solid tumors.


Assuntos
Infecções por Escherichia coli , Microbioma Gastrointestinal , Hiperuricemia , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Hiperuricemia/tratamento farmacológico , Camundongos , Oxigênio , Urato Oxidase/genética , Urato Oxidase/uso terapêutico , Ácido Úrico/metabolismo , Ácido Úrico/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-35534706

RESUMO

To evaluate the health risks of drinking water in Hanyuan County, 96 samples of peripheral drinking water were collected from 30 sites in the area. The samples were then analyzed for chemical properties including Fe, Mn, NH3-N, [Formula: see text], F-, Pb, Hg, As, Cr(VI), Cd, and so on. The health risks of ten trace elements in drinking water were probabilistically assessed using the health risk assessment model and Monte Carlo simulation. On this basis, sequential indicator simulations were used to classify the health risk levels of drinking water in the region, to conduct hierarchical management and control. The results showed that except for [Formula: see text], all other indicators met World Health Organization standards and China's drinking water sanitation standards. Drinking water presents a specific carcinogenic risk to adults, and the cumulative contribution of As and Cr(VI) exceeds 95%, and has a specific non-carcinogenic risk to children if the cumulative contribution of F-, [Formula: see text], and As exceeds 90%. Grade I, II, and III non-carcinogenic risk areas accounted for 0.89%, 24.72%, and 74.39% of the total area of Hanyuan County, respectively, while grade I, II, and III carcinogenic risk areas accounted for 27.71%, 45.56%, and 26.73% of the total Hanyuan County area, respectively. Finally, according to the health risk characteristics of each control area, corresponding zoning control suggestions were proposed.

9.
Hum Brain Mapp ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524680

RESUMO

Sleep deprivation (SD) is very common in modern society and regarded as a potential causal mechanism of several clinical disorders. Previous neuroimaging studies have explored the neural mechanisms of SD using magnetic resonance imaging (MRI) from static (comparing two MRI sessions [one after SD and one after resting wakefulness]) and dynamic (using repeated MRI during one night of SD) perspectives. Recent SD researches have focused on the dynamic functional brain organization during the resting-state scan. Our present study adopted a novel metric (temporal variability), which has been successfully applied to many clinical diseases, to examine the dynamic functional connectivity after SD in 55 normal young subjects. We found that sleep-deprived subjects showed increased regional-level temporal variability in large-scale brain regions, and decreased regional-level temporal variability in several thalamus subregions. After SD, participants exhibited enhanced intra-network temporal variability in the default mode network (DMN) and increased inter-network temporal variability in numerous subnetwork pairs. Furthermore, we found that the inter-network temporal variability between visual network and DMN was negative related with the slowest 10% respond speed (ß = -.42, p = 5.57 × 10-4 ) of the psychomotor vigilance test after SD following the stepwise regression analysis. In conclusion, our findings suggested that sleep-deprived subjects showed abnormal dynamic brain functional configuration, which provides new insights into the neural underpinnings of SD and contributes to our understanding of the pathophysiology of clinical disorders.

10.
Genome Med ; 14(1): 46, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501841

RESUMO

BACKGROUND: Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. METHODS: We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. RESULTS: We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52+ NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. CONCLUSIONS: We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system.


Assuntos
COVID-19 , Transcriptoma , Idoso , Envelhecimento/genética , Humanos , Imunidade Inata , Células Matadoras Naturais/metabolismo , Índice de Gravidade de Doença
11.
Dis Markers ; 2022: 9302733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531479

RESUMO

Cases of unpredictable, idiosyncratic liver damage of moxifloxacin (MXF) have been occasionally reported. However, the health effects of MXF exposure remain controversial. The current study examined the metabolic phenotypes and intestinal flora characteristics of hepatotoxicity induced by MXF. Rats were administered moxifloxacin hydrochloride tablets at doses of 36, 72, and 108 mg/kg body weight/day for 21 days. The levels of tricarboxylic acid cycle intermediates were decreased, whereas those of lipids (arachidonic acid, hexadecanoic acid, and linoleic acid) were increased, reflecting disorders of energy-related and lipid metabolism. Enrichment analysis of the differential metabolites suggested that butanoate metabolism was associated with MXF-induced liver injury. 16S rRNA sequencing uncovered that the diversity of gut intestinal was decreased in MXF-treated rats. Specifically, the abundance of Muribaculaceae was increased, whereas that of Lachnospiraceae, a family of butyrate-producing bacteria, was decreased. The combined serum metabonomics and gut microbiome datasets illustrated the involvement of butanoic acid and energy metabolism in the regulatory changes of the gut-liver axis associated with MXF-induced liver injury. The regulation of endogenous small molecules and intestinal flora during drug-induced liver injury was first described from the perspective of the gut-liver axis, providing a research basis for the mechanism of clinical drug-induced liver injury.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Animais , Ácido Butírico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Moxifloxacina , RNA Ribossômico 16S , Ratos
12.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563299

RESUMO

Phospholipase Dα (PLDα), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Dδ (PLDδ) can mediate the salt response in higher plants. PePLDδ was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDδ-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDδ-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H2O2 levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDδ-overexpressed plants increased the transcription of genes encoding the plasma membrane Na+/H+ antiporter (AtSOS1) and H+-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na+ extrusion and reduce K+ loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K+/Na+ homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDδ. PePLDδ-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2), 36:5 (18:2-18:3) and 36:6 (18:3-18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2) and 36:5 (18:2-18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDδ-derived PA enhanced the salinity tolerance by regulating ROS and K+/Na+ homeostasis in Arabidopsis.

13.
Micron ; 158: 103291, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35500399

RESUMO

Herein, CoCrxCuFeMnNi (x = 0, 0.5, 1.0, 1.5, and 2.0, in molar ratio) high-entropy alloys (HEAs) are fabricated by vacuum hot-pressing sintering (VHPS). The effect of Cr content on the microstructure and oxidation behavior are studied. When x ≤ 1.5 mol, the phases of the four alloys were all composed of FCC2 major phase and FCC1 secondary phase, while Cr2.0 alloy consisted of a small amount of FCC1 phase and ρ phase in addition to FCC2 main phase. The elemental segregation increased with the increase of Cr content. Cr2.0 alloy exhibited the lowest oxidation rate constants in the oxidation stage and the slow oxidation stage, which were 2.29 × 10-11 and 3.46 × 10-12 g2 cm-4 s-1, respectively, showing the best oxidation resistance. The oxidation products of CoCrxCuFeMnNi HEA system were mainly Mn4O3, Mn3O2, Cr2O3 and (M,Cr)3O4-type spinel oxides. The oxidation mechanism is mainly selective oxidation, that is, the outward diffusion of metal cations and the inward diffusion of oxygen ions. The oxidation resistance of the Cr-rich FCC1 and ρ phases is better than that of the copper-rich FCC2 phase.

14.
PLoS One ; 17(5): e0267920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35576216

RESUMO

Water resources scarcity has threatened the coordinative development of demographics, society and economy. As a typical rapidly urbanizing area and an emerging megacity in China, Chengdu is confronting the pressure of inadequate water supply. The present study divides the macroeconomic factors that affect the water resource supply and demand balance into six major subsystems: water resources supply, water demand, water drainage, population, ecological environment and economy. The combining variable interaction description and predictive simulation models are applied to simulate the water supply and demand ratio (S:D) from 2005 to 2035. Further, this study designs different development scenarios to simulate the change of S:D ratios by altering the parameter values of driving factors. The results show that: (1) the S:D ratio will decline if the current development scenario continues, implying the serious water resources shortage and the severe water supply-demand conflict in Chengdu; (2) socio-economic water demand and wastewater/rainwater reuse are the key driving parameters of S:D ratio, especially the water consumption per ten thousand yuan of industrial value-added; (3) the S:D ratio will increase from 0.92 in the current baseline scenario to 1.06 in the integrated optimization scenario in 2025, and the long-term planning brings 2035 from 0.71 to 1.03, with the proportion of unconventional water supply rise to 38% and 61%, respectively. This study can provide a decision-making tool for policy-makers to explore plausible policy scenarios necessary for bridging the gap between the water supply and demand in megacities.

15.
Sci Total Environ ; : 155671, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525342

RESUMO

It is widely thought that organo-mineral complexes (OMCs) stabilize organic matter via mineral adsorption. Recent studies have demonstrated that root exudates can activate OMCs, but the influence of OMCs on plant rhizosphere, which is among the most active areas for microbes, has not been thoroughly researched. In this study, a pot experiment using Brassica napus was conducted to investigate the effects of OMCs on plant rhizosphere. The result showed that OMC addition significantly promoted the growth of B. napus compared to the prevalent fertilization (PF, chemical fertilizer + chicken compost) treatment. Specifically, OMC addition increased the relative abundance (RA) of nitrogen-fixing bacteria and the bacterial α-diversity, and the operational taxonomic unit (OTU) group with RA > 0.5% in the OMC-treated rhizosphere was the result of a deterministic assembly process with homogeneous selection. Gene abundance related to nitrogen cycling and the soil chemical analysis demonstrated that the OMC-altered bacterial community induced nitrogen fixation and converted nitrate to ammonium. The upregulated carbon sequestration pathway genes and the increased soil microbial biomass carbon (23.68%) demonstrated that the bacterial-induced carbon storage in the rhizosphere was activated. This study shows that the addition of OMCs can influence the biogeochemical carbon and nitrogen cycling via regulating rhizosphere microorganisms in the rhizosphere. The findings provide fresh insights into the effects of OMCs on the biogeochemical cycling of important elements and suggest a promising strategy for improving soil productivity.

16.
Neuroradiology ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35441874

RESUMO

PURPOSE: Posterior cerebral artery (PCA) aneurysms are rare. This study is to evaluate the preliminary experience of braided stents applied in PCA aneurysms treatment. METHODS: Angiographic and clinical data of 28 PCA patients treated with braided stents from July 2016 and September 2020 were retrospectively analyzed. RESULTS: A total of 28 PCA aneurysms were enrolled. 22 (78.6%) aneurysms were dissecting aneurysms, while 6 (21.4%) aneurysms were saccular aneurysms. Thirty-five braided stents were implanted with dual stents implanted in 7 cases. Immediate angiographic results show that Raymond class I was obtained in 13 patients (46.4%), Raymond class II was obtained in 4 patients (14.3%), and Raymond class III was obtained in 11 patients (39.3%). Perioperative hemorrhagic events occurred in 1 patient (3.6%). Twenty-four patients (85.7%) received angiographic follow-up, and the mean follow-up time was 11.2 ± 4.9 months. Two patients (8.3%) were confirmed with IA neck recurrence, and 3 patients (12.5%) were confirmed asymptomatic parent artery occlusion (PAO). The other 19 patients were confirmed promoted occlusion with 18 Raymond class I (75%) and 1 Raymond class II (4.2%). Twenty-seven patients (96.4%) received clinical follow-up, and the mean follow-up time was 32.2 ± 13.5 months. One patient (3.7%) confirmed the death event 2 weeks after discharge. The other 27 patients (96.3%) got favorable clinical outcomes with an mRS score of 0-2. CONCLUSIONS: Braided stent-assisted coiling with a high occlusion rate and relatively low complication rate provides an alternative strategy in treating PCA aneurysms. Long-term outcomes need further randomized study with larger case numbers.

17.
Acta Biomater ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489607

RESUMO

The reduction of ROS and inflammatory factor levels plays important role in the treatment of colitis. A series of ROS-responsive lipids (ZnDPA-R) based on the thioketal structure were designed and synthesized. It was hoped that the lipidic materials could combine ROS consumption and siRNA delivery capacity to achieve synergistic treatment of colitis. The target liposomes could combine with the phosphate backbone of siRNA to form lipoplexes with the size of ∼100 nm, and could deliver siRNA cargo into the cell. The results of in vitro anti-inflammatory experiments showed that the lipids may effectively consume ROS in cells. Meanwhile, the lipoplexes significantly reduced the expression levels of TNF-α mRNA and related inflammatory factors in macrophages. After PEGylation, the lipoplex was used for the treatment of mouse colitis, and biodistribution results proved that the lipoplexes effectively aggregated in the intestine. The delivery system could not only response to the high ROS level at colitis via thioketal breaking, but also could assist in the treatment of inflammation by ROS consumption. The treatment results revealed that the levels of TNF-α mRNA and related inflammatory factors at the colon lesion were largely reduced, and the inflammatory symptoms were significantly relieved. Hematology test results indicated that the treatment was safe and induced no obvious side effects on mice. This study may shed light on the synergistic treatment for colitis via anti-inflammatory siRNA delivery and ROS depletion strategies. STATEMENT OF SIGNIFICANCE: Downregulation of inflammatory factors and reactive oxygen species (ROS) levels is critical in treating colitis. In the present study, a series of ROS-responsive lipid molecules based on the Zn-DPA headgroup and thioketal linkage were synthesized for delivering TNF-α siRNA and for treating colitis. In addition to silencing the expression of TNF-α mRNA and the related inflammatory factors, the material also achieved synergistic treatment by simultaneous consumption of ROS in the colon lesion. In vitro cell experiments and in vivo colitis treatment in mice showed that the lipoplex exerted a satisfactory therapeutic effect on colitis, and the symptoms of colitis in mice were significantly alleviated. The present study may shed light on the synergistic treatment for colitis through anti-inflammatory siRNA delivery and ROS depletion strategies.

18.
Med Sci Monit ; 28: e936373, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35396343

RESUMO

Loudness recruitment is a common symptom of hearing loss induced by cochlear lesions, which is defined as an abnormally fast growth of loudness perception of sound intensity. This is different from hyperacusis, which is defined as "abnormal intolerance to regular noises" or "extreme amplification of sounds that are comfortable to the average individual". Although both are characterized by abnormally high sound amplification, the mechanisms of occurrence are distinct. Damage to the outer hair cells alters the nonlinear characteristics of the basilar membrane, resulting in aberrant auditory nerve responses that may be connected to loudness recruitment. In contrast, hyperacusis is an aberrant condition characterized by maladaptation of the central auditory system. Peripheral injury can produce fluctuations in loudness recruitment, but this is not always the source of hyperacusis. Hyperacusis can also be accompanied by aversion to sound and fear of sound stimuli, in which the limbic system may play a critical role. This brief review aims to present the current status of the neurobiological mechanisms that distinguish between loudness recruitment and hyperacusis.


Assuntos
Perda Auditiva , Hiperacusia , Estimulação Acústica , Nervo Coclear , Humanos , Percepção Sonora/fisiologia
19.
Front Pharmacol ; 13: 869200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462887

RESUMO

Background: The pathological differences between Crohn's disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data. Methods: Kruskal-Wallis and Dunnett's tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort. Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR. Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

20.
Ecotoxicol Environ Saf ; 236: 113451, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35378401

RESUMO

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P < 0.05. Of note, the human serum circRNA dataset encompassed 28 of 243 circRNAs. GEO (GSE102660) validation revealed two highly expressed circRNAs (P < 0.05) in the IPF case group. Furthermore, at the enlarged sample validation stage, hsa_circ_0058493 was highly expressed in both silicosis and IPF cases (silicosis: P = 1.16 × 10-6; IPF: P = 7.46 × 10-5). Additionally, hsa_circ_0058493 expression was significantly increased in MRC-5 cells upon TGF-ß1 treatment, while hsa_circ_0058493 knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process. These shreds of evidence indicated that hsa_circ_0058493 might serve as a novel biomarker for diagnosing silicosis and IPF.


Assuntos
Fibrose Pulmonar Idiopática , Silicose , Biomarcadores/metabolismo , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/genética , RNA/genética , RNA Circular/genética , RNA-Seq , Silicose/genética
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