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1.
Chemosphere ; : 134759, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35490747

RESUMO

The emission of condensable particulate matter (CPM) and its environmental impacts are arousing concern in China with the effective control of filter particulate matter (FPM). This study established an up-to-date and unit-based CPM emission inventory for industrial sectors and systematically evaluated the effects of CPM on primary and secondary PM2.5 in China. In 2020, the national CPM emissions total for industrial sectors was estimated to be 0.98 Tg with uncertainty from -49% to 66%, including 0.62 Tg of organic CPM (CPMorg) and 0.36 Tg of inorganic CPM (CPMin). Totals of 62%, 23% and 8% CPM were emitted from coal-fired power plants, coal-fired industrial boilers and sinter plants, respectively. By filling CPM emissions in PM2.5 simulation, the normalized mean bias (NMB) of model to observation was improved from -27% to -14% in East, North and Central China. The 4 µg/m3 PM2.5 concentration was attributed to CPM emissions in this region, accounting for 10% of observations. On "polluted" days (PM2.5>75 µg/m3), industrial CPM emissions can contribute 7 µg/m3 PM2.5 in North China. Therefore, China should focus on controlling CPM from coal combustion to ensure continuous air quality improvement.

2.
Aging (Albany NY) ; 14(undefined)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504194

RESUMO

Aging causes a decline in ovarian function and may contribute to ovarian failure and infertility. We investigated the effect of menstrual blood-derived mesenchymal stem cells (MenSCs) and their mitochondria on ovarian function in aged mice. We performed two treatment protocols: i) ovaries of recipient aged mice were treated in vivo with MenSCs 3D alginate gel; ii) ovaries were injected with mitochondria suspension and then incubated with mitochondrial 3D gel. Seven days after treatment, ovaries were harvested for histological assessment by HE staining and transcriptomic analysis by RNA-seq. Our data showed that after incubation with stem cell 3D gel, the MenSCs could be detected in the recipient mouse ovary. HE staining showed that the follicular state of aging ovary improved with both treatments. RNA-seq analysis showed that mitochondrial pathway-related genes were upregulated and significantly enriched in the ovaries treated by MenSCs or their mitochondria. Conclusions: Treatment with MenSCs or their mitochondria can enhance the expression of mitochondrial pathway-related genes and promote the recovery of ovarian function in aged mice.

3.
RSC Adv ; 12(16): 9660-9670, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35424931

RESUMO

A breakthrough in enhancing visible-light photocatalysis of wide-bandgap semiconductors such as prototypical titania (TiO2) via cocatalyst decoration is still challenged by insufficient heterojunctions and inevitable interfacial transport issues. Herein, we report a novel TiO2-based composite material composed of in situ generated polymorphic nanodomains including carbon nitride (C3N4) and (001)/(101)-faceted anatase nanocrystals. The introduction of ultrafine C3N4 results in the generation of many oxygen vacancies in the TiO2 lattice, and simultaneously induces the exposure and growth of anatase TiO2(001) facets with high surface energy. The photocatalytic performance of C3N4-induced TiO2 for degradation of 2,4-dichlorophenol under visible-light irradiation was tested, its apparent rate being up to 1.49 × 10-2 min-1, almost 3.8 times as high as that for the pure TiO2 nanofibers. More significantly, even under low operation temperature and after a long-term photocatalytic process, the composite still exhibits exceptional degradation efficiency and stability. The normalized degradation efficiency and effective lifespan of the composite photocatalyst are far superior to other reported modified photocatalysts.

5.
Int J Biol Macromol ; 206: 148-158, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35227703

RESUMO

This study evaluated quality attributes and in vivo antioxidant activity of Auricularia cornea var. Li polysaccharide (ACP)-fortified set yogurt during 21 days of storage (4 °C). Set yogurt was manufactured using a commercial yogurt culture, and 3% (w/v) ACP was added. Physicochemical (pH, titratable acidity, and water-holding capacity), textural, rheological, microstructural, flavor, and antioxidant properties of set yogurt were investigated. The results showed that the addition of ACP significantly enhanced WHC, viscosity, firmness, and cohesiveness, while inhibiting post-acidification of set yogurt during storage. The yogurt supplemented with ACP showed a larger hysteresis area and higher G' and G″ values, formed a porous, dense, mesh-like structure and exhibited a unique mushroom flavor. Antioxidant results showed that administration of ACP-fortified yogurt significantly decreased serum alanine aminotransferase and aspartate aminotransferase enzyme activities and malondialdehyde levels, while increasing superoxide dismutase, catalase, phospholipid hydroperoxide glutathione peroxidase, and total antioxidant capacity in the liver and hippocampus of the mice. ACP-fortified yogurt might alleviate hepatic damage and hippocampal neuroinflammation induced by d-galactose. Additionally, ACP-fortified yogurt downregulated the expression of Keap1 and upregulated the expression of Nrf2 and HO-1 in the liver. In conclusion, ACP may be used as an ingredient to produce yogurt with desired properties.


Assuntos
Antioxidantes , Iogurte , Animais , Antioxidantes/farmacologia , Auricularia , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2 , Polissacarídeos/química , Polissacarídeos/farmacologia
6.
Environ Sci Technol ; 56(8): 4980-4987, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35349262

RESUMO

Photoelectrocatalysis (PEC) is an efficient way to address various pollutants. Surface-adsorbed atomic hydrogen (H*) and hydroxyl radicals (•OH) play a key role in the PEC process. However, the instability of H* and low production of •OH considerably limit the PEC efficiency. In this study, we noted that incorporating oxygen atoms could regulate the behavior of H* by creating a locally favorable electron-rich state of S atoms in the SnS2 catalyst. The finely modulated H* led to a 12-fold decrease in the overpotential of H2O2 generation (H*-OOH*-H2O2-•OH) by decreasing the activation energy barrier of OOH* (rate-determining step). Considering density functional theory calculations, an H*-•OH redox pair suitable for a wide pH range (3-11) was successfully constructed based on the photocathode. The optimal SnS1.85O0.15 AL@TNA photocathode exhibited a ∼90% reduction in Cr(VI) in 10 min and ∼70% TOC removal of 4-nitrophenol, nearly 2- and 3-fold higher than that without oxygen incorporation. Electron spin resonance spectrometry and radical quenching experiments verified that H* and the derived •OH via 1-electron and 3-electron reduction were the main active species. Operando Raman spectroscopy confirmed that the stable SnO2 phase helped constantly activate the production of H* and •OH.

7.
Quant Imaging Med Surg ; 12(2): 1579-1584, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35111650

RESUMO

The susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) in the middle cerebral artery is a reliable biomarker for cardioembolic ischemic stroke. As for the basilar artery (BA), the magnetic susceptibility-related image signs, the quantitative evaluation of the corresponding thrombus, and their prediction of cardioembolism require further study. This study aimed to assess thrombus susceptibility-related image characteristics using susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) MRI in acute BA occlusion and analyze their associations with cardioembolic ischemic stroke. A total of 41 consecutive acute ischemic stroke patients with BA occlusion within 48 h of onset were recruited. A three-dimensional (3D) multi-echo scan on a 3.0T MRI scanner was applied to all participants, and the quantitative susceptibility value of the BA thrombus was computed using QSM. The presence and diameter of SWI SVS in patients with cardioembolic stroke were not significantly different from those with other etiologies. While BA thrombus's susceptibility in patients with cardioembolic stroke was significantly higher than that in patients with non-cardioembolic stroke (0.42±0.09 vs. 0.22±0.11 ppm, P<0.001). Receiver operating characteristic (ROC) curve analysis showed that the optimal cutoff value for the QSM susceptibility of BA thrombus in the identification of cardioembolic stroke was 0.33 ppm, with sensitivity, specificity, positive predictive value, and negative predictive value of 81.8% (95% CI: 48.2% to 97.7%), 81.3% (95% CI: 63.6% to 92.8%), 60.0% (95% CI: 40.9% to 76.5%), and 92.9% (95% CI: 78.6% to 97.9%), respectively. Magnetic susceptibility in BA thrombus could discriminate cardiogenic embolism from other stroke subtypes, thus becoming a novel biomarker of cardiogenic stroke in acute BA occlusion.

8.
J Agric Food Chem ; 70(8): 2630-2642, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35187930

RESUMO

Mitophagy has a neuroprotective effect on reactive oxygen species (ROS)-induced neurodegenerative diseases. The walnut-derived polypeptide (TW-7) has antioxidant activity and protects nerves by promoting autophagy. However, its action mechanism against oxidative stress through mitophagy remains obscure. Therefore, we aimed to assess the effects of TW-7 on HT-22 cells under oxidative stress. Mitochondrial ultrastructure and cristae number were observed by transmission electron microscopy. The results showed that TW-7 (100 µM) restored the fluorescence intensity of the mitochondrial membrane potential to 0.99 ± 0.04 (P < 0.05), decreased H2O2-induced opening of mitochondrial permeability transition pores, and inhibited mitochondrial bioenergetic deficits. Moreover, it significantly increased activities of antioxidant enzymes to 186.88 ± 5.40 U/mgprot, 40.08 ± 0.87 mU/mgprot, and 23.57 ± 0.77 U/mgprot (P < 0.05), based on superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) assay results, respectively. Consistently, it decreased cellular and mitochondrial ROS levels by 51.71 ± 0.81 and 49.75 ± 0.69% (P < 0.05). TW-7 also downregulated C-Jun N-terminal kinase (JNK) phosphorylation and activated PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy in H2O2-induced HT-22 cells treated with JNK activator (anisomycin) and inhibitor (SP600125). Furthermore, TW-7 inhibited the mitochondrial apoptosis pathway by downregulation of the cytoplasmic cytochrome C, caspase-9, and cleaved-caspase-3 expression. Additionally, BDNF and SNAP-25 levels significantly increased to protect the synaptic function. Collectively, TW-7 improved oxidative stress-mediated nerve cell injury via JNK-regulated PINK1-mediated mitophagy.


Assuntos
Juglans , Mitofagia , Apoptose , Peróxido de Hidrogênio/toxicidade , Juglans/metabolismo , MAP Quinase Quinase 4/metabolismo , Estresse Oxidativo , Peptídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
J Agric Food Chem ; 70(7): 2197-2210, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35118857

RESUMO

This study investigated the effects of the exopolysaccharide from Lactiplantibacillus plantarum JLAU103 (EPS103) on the intestinal immune response, oxidative stress, intestinal mucosal barrier, and microbial community in cyclophosphamide-induced immune-suppressed mice. The results showed that EPS103 promoted the secretion of cytokines and the generation of secretory immunoglobulin A and mucin-2 in the small intestine of mice, which might be related to the activation of the MAPK pathway. Additionally, EPS103 protected against oxidative stress by activating antioxidation enzymes and Nrf2/Keap1 pathways. It also improved the intestinal physical barrier functions via regulating the ratio of villous height to crypt depth and upregulating the expression of tight-junction proteins. Meanwhile, EPS103 promoted the generation of short-chain fatty acids (SCFAs) and modulated the constituents of gut microbiota. These results suggested that EPS103 may modulate the intestinal immunoresponse relying on the regulation of SCFA production and gut microbiota in immunosuppressed mice, resulting in the activation of systemic immunity.


Assuntos
Microbiota , Fator 2 Relacionado a NF-E2 , Animais , Ciclofosfamida/toxicidade , Imunidade , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
10.
Quant Imaging Med Surg ; 12(1): 550-557, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993100

RESUMO

BACKGROUND: The hypointense blooming signal of thrombi on susceptibility-weighted imaging (SWI), known as the susceptibility vessel sign (SVS), is predictive of cardioembolic stroke. The SVS originates from the local magnetic susceptibility effect; thus, the susceptibility value of thrombi may provide useful information in discriminating stroke etiology. We aim to utilize quantitative susceptibility mapping (QSM) to assess thrombus's susceptibility value in acute ischemic stroke patients and explore the relationship of thrombus susceptibility with cardioembolic stroke. METHODS: From 2018 to 2020, 132 consecutive acute ischemic stroke patients with middle cerebral artery occlusion were recruited within 48 hours of onset. All patients underwent a three-dimensional multi-echo SWI scan using a 3 Tesla magnetic resonance imaging scanner. The SVS presence and the diameter of the SVS-related hypointense signal were assessed on SWI. QSM was applied to compute the susceptibility value of the thrombus. The receiver operating characteristic (ROC) methodology was used to define the optimal cutoff value of the susceptibility in QSM and the diameter on SWI for predicting cardioembolic stroke. RESULTS: The SVS was identified in 93 (70.5%) patients with symptomatic middle cerebral artery occlusion and was significantly associated with cardioembolism. The hyperintense signal on QSM in the corresponding middle cerebral artery occlusion was present in 116 (87.9%) patients. ROC analysis indicated that thrombus susceptibility had a greater area under the curve than that of the SVS diameter (0.88 vs. 0.70, P<0.001) and that the optimal cutoff value of thrombus susceptibility for cardioembolism was 0.35 ppm. Multivariate analysis demonstrated that thrombus susceptibility (≥0.35 ppm) was an independent predictor of cardioembolic stroke (odds ratio =20.75; 95% CI, 7.19-59.87; P<0.001), with sensitivity, specificity, a positive predictive value, and a negative predictive value of 85.2%, 80.8%, 75.4%, and 88.7%, respectively, while the SVS presence showed sensitivity, specificity, a positive predictive value, and a negative predictive value of 90.7%, 43.6%, 87.2%, and 52.7%, respectively. CONCLUSIONS: Thrombus susceptibility provides superior diagnostic performance over the SVS for discriminating between cardioembolism and other stroke subtypes. Quantitative susceptibility measurements of thrombi may help predict cardioembolic stroke in patients with acute middle cerebral artery occlusion.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35066595

RESUMO

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) levels were determined in surface water, groundwater and sediments of the Jin River Basin, southeastern China. PFOA was detected in most of the samples, and its concentrations ranged from 0.53 to 8.77 ng/L, 0.26 to 15.1 ng/L and not detected (ND) to 23.9 ng/g in surface water, groundwater and sediments, respectively. Unlike PFOA, the detection frequency of PFOS was lower than 32%, and its concentrations ranged from ND to 2.56 ng/L, ND to 7.01 ng/L, ND to 11.1 ng/g in surface water, groundwater and sediments, respectively. The environmental risk assessment showed that PFOA could pose a high risk to surface water and groundwater, and both PFOA and PFOS posed a high risk to sediments. Moreover, the adults living in the Jin River Basin were at insignificant health risk to exposure to PFOA and PFOS through water consumption.

12.
Clin Exp Hypertens ; 44(1): 46-56, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34648405

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a rare and deadly disease characterized by remodeling of the pulmonary vasculature and increased pulmonary artery pressure. hypobaric pulmonary hypertension (HPH) is clinically classified as group 4 of pulmonary hypertension and has a poor prognosis . Previous reports showed that HPH was associated with increased endoplasmic reticulum (ER) stress. The protein kinase R-like endoplasmic reticulum kinase (PERK) is an ER-associated stress protein. However, to date, its physiological effects on HPH and RVF development remains unknown. This study aimed to assess PERK's role in HPH and RV function using in vivo experimental model. METHODS: Perk-knockout male Sprague-Dawley rats were generated and were housed in either a hypobaric chamber or in a normoxic environment. After stimulation for 4 weeks, the hemodynamic parameters of the rats were measured. The heart and lungs were harvested for pathological observation. Blood was collected for the detection of inflammatory indexes. The right ventricle tissue was collected to assess phosphorylated-AKT, ROCK1, ET1, and MMP2 protein expression. RESULTS: WE FIRSTLY GENERATED PERK+/− RATS,: Under normal conditions, Perk+/- rats showed no changes in mPAP(mean pulmonary artery pressure), RVHI(Right ventricular hypertrophy index), cardiomyocyte size and interstitial fibrosis, and pulmonary vascular remodeling. However, in response to chronic hypoxia, Perk+/- rats exhibited decreased in mPAP, RVHI, ventricular fibrosis, and lung remodeling compared to wild-type rats. Perk+/- rats also showed lower expression of phosphor-AKT, ROCK1, ET1, and MMP2 protein in response to chronic hypoxia. CONCLUSIONS: These findings suggest that Perk heterozygosity protects against HPH and Perk may be a suitable target for treating HPH.


Assuntos
Hipertensão Pulmonar , Hipertrofia Ventricular Direita , Animais , Hipertensão Pulmonar/genética , Hipertrofia Ventricular Direita/genética , Hipóxia/complicações , Hipóxia/genética , Pulmão , Masculino , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley
13.
Hum Brain Mapp ; 43(3): 1047-1060, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34854172

RESUMO

Brain iron dyshomeostasis disrupts various critical cellular functions, and age-related iron accumulation may contribute to deficient neurotransmission and cell death. While recent studies have linked excessive brain iron to cognitive function in the context of neurodegenerative disease, little is known regarding the role of brain iron accumulation in cognitive aging in healthy adults. Further, previous studies have focused primarily on deep gray matter regions, where the level of iron deposition is highest. However, recent evidence suggests that cortical iron may also contribute to cognitive deficit and neurodegenerative disease. Here, we used quantitative susceptibility mapping (QSM) to measure brain iron in 67 healthy participants 18-78 years of age. Speed-dependent (fluid) cognition was assessed from a battery of 12 psychometric and computer-based tests. From voxelwise QSM analyses, we found that QSM susceptibility values were negatively associated with fluid cognition in the right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices. Mediation analysis indicated that susceptibility in the right inferior temporal gyrus was a significant mediator of the relation between age and fluid cognition, and similar effects were evident for the left inferior temporal gyrus at a lower statistical threshold. Additionally, age and right inferior temporal gyrus susceptibility interacted to predict fluid cognition, such that brain iron was negatively associated with a cognitive decline for adults over 45 years of age. These findings suggest that iron may have a mediating role in cognitive decline and may be an early biomarker of neurodegenerative disease.


Assuntos
Envelhecimento/fisiologia , Córtex Cerebral/fisiologia , Disfunção Cognitiva , Inteligência/fisiologia , Ferro/metabolismo , Putamen/fisiologia , Adolescente , Adulto , Idoso , Envelhecimento/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Putamen/diagnóstico por imagem , Putamen/metabolismo , Putamen/fisiopatologia , Adulto Jovem
14.
J Hazard Mater ; 422: 126974, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449332

RESUMO

Atomic hydrogen (H*) plays a vital role in the synchronous redox of metallic ions and organic molecules. However, H* is extremely unstable as it is easily converted to hydrogen. Herein, we designed a novel strategy for the effective stabilization of H* to enhance its utility. The synthesized Pd nanoparticles grown on the defective MoS2 (DMS) of TiO2 nanowire arrays (TNA) (TNA/DMS/Pd) photocathode exhibited rapid Cr(VI) reduction (~95% in 10 min) and bisphenol A (BPA) oxidation (~97% in 30 min), with the kinetic constants almost 24- and 6-fold higher than those of the TNA photocathode, respectively. This superior performances could be attributed to: (i) the generated interface heterojunctions between TNA and DMS boosted the separation efficiencies of photogenerated electrons, thereby supplying abundant valance electrons to lower the overpotential to create a suitable microenvironment for H* generation; (ii) the stabilization of H* by Pd nanoparticles resulted in a significant increase in the yield of hydroxyl radical (•OH). This research provides a new strategy for the effective utilization of H* toward rapid reduction of heavy metals and synchronous oxidation of the refractory organics.

15.
Genome Biol ; 22(1): 321, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34847932

RESUMO

Recent advances in single-cell biotechnologies have resulted in high-dimensional datasets with increased complexity, making feature selection an essential technique for single-cell data analysis. Here, we revisit feature selection techniques and summarise recent developments. We review their application to a range of single-cell data types generated from traditional cytometry and imaging technologies and the latest array of single-cell omics technologies. We highlight some of the challenges and future directions and finally consider their scalability and make general recommendations on each type of feature selection method. We hope this review stimulates future research and application of feature selection in the single-cell era.


Assuntos
Análise de Célula Única/métodos , Biologia Computacional/métodos , Epigenômica , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Transcriptoma
16.
Comput Math Methods Med ; 2021: 1284149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912470

RESUMO

OBJECTIVE: This study evaluated the efficacy and safety of CD combined with bone marrow stem cells in the treatment of femoral head necrosis by systematic review and meta-analysis. Methodology. PubMed, The Cochrane Library, Embase, CNKI, Google Scholar and MEDLINE, etc. databases were searched for clinical randomized controlled trials (RCTs) comparing core decompression combined with autologous bone marrow mesenchymal stem cells versus core decompression alone in the treatment of femoral head necrosis. The retrieval period is from the establishment of each database to May 20, 2021. After literature was extracted and literature quality was evaluated, meta-analysis was conducted by using RevMan5.3 software. RESULTS: A total of 420 osteonecrosis of the femoral head 452 patients' data were collected from all studies. Compared with the core decompression alone group, the CD combined with bone marrow stem cell showed marked reduction in the Visual analog scale (VAS), enhanced Harris hip score (HHS) at 12 months and 24 months, slowed down the progression of the disease, decreased the number of hips conversed to total hip arthroplasty (THA) in the future. CONCLUSION: Core decompression therapy is a very effective and safe treatment process used for ONFH. Moreover, CD combined autologous bone marrow stem cell transplantation can improve the survival rate of the necrotic head, reduce hip pain and delay the disease progression, the rate of THA postoperatively.


Assuntos
Descompressão Cirúrgica/métodos , Necrose da Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/terapia , Transplante de Células-Tronco Mesenquimais , Artroplastia de Quadril/estatística & dados numéricos , Autoenxertos , Terapia Combinada , Biologia Computacional , Descompressão Cirúrgica/estatística & dados numéricos , Progressão da Doença , Necrose da Cabeça do Fêmur/fisiopatologia , Humanos , Medição da Dor , Resultado do Tratamento
17.
Front Med (Lausanne) ; 8: 742436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805208

RESUMO

High-altitude pulmonary hypertension (HAPH) is a complication arising from an inability to acclimatize to high altitude and is associated with high morbidity and mortality. We aimed to analyze the effects of macitentan, selexipag, riociguat, and reoxygenation on HAPH, and to screen possible targets of these treatments for future drug screening. Rats were subjected to hypobaric hypoxia for 35 days to induce HAPH, and treated with vehicle or selexipag, macitentan, riociguat, or with reoxygenation, from days 21 to 35. Selexipag, macitentan, and reoxygenation prevented an increase in mean pulmonary artery pressure and hypoxia-induced right ventricular hypertrophy, compared to the vehicle. Riociguat had little effect. RNA-seq and proteomics revealed strong correlations between responses to the three drugs, which had almost identical effects. GO-enrichment revealed that the differentially expressed genes included those involved in metabolic regulation, transcription, and translation. Various molecular pathways were annotated. Selexipag, macitentan, and reoxygenation ameliorated HAPH. Serpina1, Cryz, and Cmc1 were identified, via multi-omics screening, as key genes involved in HAPH. These findings provide new insights into the targeted drug mechanisms in HAPH.

18.
iScience ; 24(10): 103094, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34622149

RESUMO

FeRIC (Ferritin iron Redistribution to Ion Channels) is a magnetogenetic technique that uses radiofrequency (RF) alternating magnetic fields to activate the transient receptor potential channels, TRPV1 and TRPV4, coupled to cellular ferritins. In cells expressing ferritin-tagged TRPV, RF stimulation increases the cytosolic Ca2+ levels via a biochemical pathway. The interaction between RF and ferritin increases the free cytosolic iron levels that, in turn, trigger chemical reactions producing reactive oxygen species and oxidized lipids that activate the ferritin-tagged TRPV. In this pathway, it is expected that experimental factors that disturb the ferritin expression, the ferritin iron load, the TRPV functional expression, or the cellular redox state will impact the efficiency of RF in activating ferritin-tagged TRPV. Here, we examined several experimental factors that either enhance or abolish the RF control of ferritin-tagged TRPV. The findings may help optimize and establish reproducible magnetogenetic protocols.

19.
Front Cell Infect Microbiol ; 11: 708088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692558

RESUMO

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.


Assuntos
Doenças das Artérias Carótidas , Microbioma Gastrointestinal , Biomarcadores , Clostridiales , Humanos , Metaboloma , Metabolômica
20.
Basic Res Cardiol ; 116(1): 53, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546460

RESUMO

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-ß signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-ß-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-ß/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-ß signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-ß signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-ß pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-ß-associated mechanisms.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Proteínas Morfogenéticas Ósseas , Células Endoteliais , Humanos , Hipertensão Pulmonar/genética , Hipóxia , MicroRNAs/genética , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Artéria Pulmonar , Fator de Crescimento Transformador beta
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