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1.
Neurol Res ; : 1-9, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33825678

RESUMEN

Objective: The purpose of our study was to distinguish the changes in the microstructure of the cingulate cortex in patients with mild cognitive impairment (MCI) induced by cerebral small vessel disease (CSVD).Method: 80 patients were diagnosed with CSVD in this study, including 55 patients with MCI and 25 patients without MCI. Diffusion kurtosis imaging (DKI) and Montreal cognitive assessment (MoCA) were performed in all patients. The anterior cingulate gyrus, posterior cingulate gyrus and middle cingulate gyrus were selected as the regions of interest, and some parameters were recorded.Results: Compared with the non-MCI group, the MCI group mainly showed obviously higher mean diffusion (MD) and radial diffusion (RD) values (P = 0.022 and P = 0.029) but lower fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK) and radial kurtosis (RK) values (P = 0.047, P = 0.001, P < 0.01, and P = 0.001, respectively) in the right anterior cingulate gyrus. Meanwhile, in the right posterior cingulate gyrus, the MCI group also showed higher axial diffusion (AD) and MD (P = 0.027 and P = 0.030) and lower AK (P = 0.014). Additionally, negative correlations of AD, MD, and RD with MoCA scores and positive correlations of FA, AK, MK and RK with MoCA scores were observed in some regions of the cingulate gyrus.Conclusions: DKI is a good method to examine microstructural damage in the cingulate cortex, and some parameters of DKI may be used as imaging biomarkers to detect early MCI in patients with CSVD.

2.
Artículo en Chino | MEDLINE | ID: mdl-33794610

RESUMEN

Objective:To explore the clinical features of cephalic and facial limited langerhans cell histiocytosis (LCH) in children for improving its diagnosis and treatment. Methods:Clinical data of 8 children with cephalic and facial limited LCH were retrospectively analyzed, including the onset time of disease, lesion location, imaging data, clinical manifestations and treatment strategies. Results:One case was preliminarily diagnosed as chronic inflammation with nasal back lesions, then conformed by repeated surgical pathology. Six cases were found to have simple cephalic and facial lumps without pain and swelling. One case was found to have temporal lump with suppurate in the lateral auditory canal. Five cases were treated with surgical excision of lesions. Three cases were treated with surgical excision of lesions, and continued with chemotherapy after confirmed pathological diagnosis. All cases were followed up for 2-3 years with good prognosis. Conclusion:Cephalic and facial limited LCH in children was easy to be misdiagnosed and should be regarded as animportant differential diagnosis of cephalic and facial lumps. Good outcome is achieved by treatment with surgical resection combined with adjuvant chemotherapy.


Asunto(s)
Histiocitosis de Células de Langerhans , Niño , Conducto Auditivo Externo , Cara , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/terapia , Humanos , Dolor , Estudios Retrospectivos
3.
J Dent ; 108: 103653, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33798641

RESUMEN

OBJECTIVES: An experimental tricalcium silicate and dicalcium silicate-containing endodontic putty has been designed to overcome the issue of reduced shelf life after exposure to atmospheric moisture during repeated opening of the container for clinical retrieval. The present study examined the effects of this experimental hydraulic putty on the mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells (hDPSCs), by comparing the cellular responses with a commercially available putty (EndoSequence BC RRM Putty). METHODS: The osteogenic potential of hDPSCs that had been exposed to the putties was examined using quantitative reverse-transcription polymerase chain reaction for osteogenic gene expressions and western blot for osteogenic protein expressions. Alkaline phosphatase activity assay and alizarin red S staining were performed to detect changes in production of the intracellular enzyme and extracellular matrix mineralization respectively. RESULTS: Osteogenic differentiation of the hDPSCs was significantly enhanced after exposure to the pre-mixed hydraulic putties, with no significant difference between these two examined putties. CONCLUSIONS: The experimental hydraulic tricalcium silicate putty enhances osteogenic differentiation of hDPSCs to the same extent as a commercially available tricalcium silicate putty. CLINICAL SIGNIFICANCE: The experimental hydraulic putty appears to be an alternative to the commercial putty when used for applications involving the regeneration of bone in endodontics. Animal models are required for validating its potential in enhancing osteogenesis in vivo.

4.
Plant Signal Behav ; : 1891769, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33818288

RESUMEN

Late embryogenesis abundant (LEA) proteins play important roles in plant defense response to drought stress. However, genome-wide identification of the LEA gene family was not revealed in Salvia miltiorrhiza. In this study, 61 SmLEA genes were identified from S. miltiorrhiza and divided into 7 subfamilies according to their conserved domains and phylogenetic relationships. SmLEA genes contained the LEA conserved motifs and few introns. SmLEA genes of the same subfamilies had similar gene structures and predicted subcellular locations. Our results indicated that the promoters of SmLEA genes contained various cis-acting elements associated with abiotic stress response. In addition, RNA-seq and real-time PCR results suggested that SmLEA genes are specifically expressed in different tissue, and most SmLEA genes can be induced by drought stress. These results provide a valuable foundation for future functional investigations of SmLEA genes and drought stress-resistant breeding of S. miltiorrhiza.

5.
Appl Opt ; 60(10): 2854-2860, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33798164

RESUMEN

A traditional beacon location method is difficult to apply to a deep space optical communications link due to the high laser power required for long distances. The use of natural celestial bodies as beacon images can solve this problem. The correct location of the beacon is critical to establish and maintain an optical communications link. Therefore, in this paper we propose an approach to determine the location of a natural celestial beacon. To identify a beacon in an uncertain region, the phase correlation between the detected and reference images is applied. The influence of an image translation is eliminated through a Fourier transform, and the scaling and rotation are converted into the translation and solved using a log-polar transformation and phase correlation, respectively. The availability of a new approach is verified by the experiment. A field-programmable gate array embedded processing system is designed to realize the proposed algorithm. When the image noise is considered, the success probability of the algorithm can reach more than 96%. We believe this work is beneficial for deep space optical communications system design.

6.
Postgrad Med ; : 1-10, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33851902

RESUMEN

Objectives: We aimed to investigate the relationship between obstructive sleep apnea (OSA) risk and respiratory inflammation evaluated by the exhaled breath condensate (EBC) interleukin-6 (IL-6) and plasma surfactant protein-D (SP-D), based on the Berlin questionnaire (BQ) screening values in an adult, urban community in Beijing, China.Methods: Volunteers aged >40 years were recruited from the Shichahai community of central Beijing (Registration number: NCT04832711). Their general information and disease history were recorded. OSA risk was assessed using the BQ. IL-6 in EBC and plasma SP-D were d etected by enzyme-linked immunoassay through specimens collected while fasting. The differences in IL-6 and SP-D values between high-risk and low-risk groups for OSA were compared, and the factors affecting their values were analyzed.Results: Among 1,239 participants, 18.8% of participants were in the high-risk group. There were more participants with higher body mass index, chronic hypertension, coronary heart disease, and diabetes in the high-risk group than in the low-risk group (P < 0.05). There were no significant differences in EBC IL-6 and plasma SP-D between the high- and low-OSA risk groups (p > 0.05). After adjustment for age, sex and chronic comorbidities, multivariate logistic regression showed that there was no correlation between risk of OSA and IL-6 in EBC. However, the risk of OSA (odds ratio [OR] [95% CI]: 1.69 [1.15,2.48]; ß = 0.522) and BMI (OR [95%CI]: 0.94 [0.91,0.98]; ß = -0.061) were independently associated with plasma SP-D level (p < 0.05 for both). Stratification analysis showed that OSA risk were independently associated with plasma SP-D levels in participants <65 years, or men, or participants with BMI<25.Conclusion: This study showed that plasma SP-D, an inflammation biomarker, was associated with risk of OSA and BMI in a Chinese central urban community.The relationship between the risk of OSA and respiratory inflammation in community populations needs to be further evaluated.

7.
J Food Sci ; 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33856047

RESUMEN

This study investigated the influence of sarcoplasmic proteins (SPs) treated by the oxidation system (0.1 mmol/L FeCl3 , 0.1 mmol/L ascorbic acid, and 0, 1, 5, 10 mmol/L H2 O2 ) on the properties of pork myofibrillar proteins (MPs) gel. After oxidation treatment, the SPs showed an increased in carbonyl content and a decreased in total sulfhydryl content, coupled with the cross-linking of protein components by disulfide bonds and covalent bonds. The MPs gel with SPs oxidized at 1 mmol/L H2 O2 exhibited the maximal strength while the minimal water holding capacity (WHC). The WHC of MPs gel was significantly decreased with increasing SPs oxidation, leading to the increase of free water and the decrease of immobilized water in the gel system. The microstructures of MPs gels with moderately (1 mmol/L H2 O2 ) oxidized SPs showed a more compact and smaller pore gel network than MPs alone, suggesting adding oxidized SPs can expel water trapped in the gel. Furthermore, the environmental polarity of aliphatic C-H groups increased with SPs oxidation.

8.
BMC Med Inform Decis Mak ; 21(1): 127, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33845834

RESUMEN

OBJECTIVE: To explore an effective algorithm based on artificial neural network to pick correctly the minority of pregnant women with SLE suffering fetal loss outcomes from the majority with live birth and train a well behaved model as a clinical decision assistant. METHODS: We integrated the thoughts of comparative and focused study into the artificial neural network and presented an effective algorithm aiming at imbalanced learning in small dataset. RESULTS: We collected 469 non-trivial pregnant patients with SLE, where 420 had live-birth outcomes and the other 49 patients ended in fetal loss. A well trained imbalanced-learning model had a high sensitivity of 19/21 ([Formula: see text]) for the identification of patients with fetal loss outcomes. DISCUSSION: The misprediction of the two patients was explainable. Algorithm improvements in artificial neural network framework enhanced the identification in imbalanced learning problems and the external validation increased the reliability of algorithm. CONCLUSION: The well-trained model was fully qualified to assist healthcare providers to make timely and accurate decisions.

9.
Environ Sci Technol ; 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33724005

RESUMEN

Purposively designing environmental advanced materials and elucidating the underlying reactivity mechanism at the atomic level allows for the further optimization of the removal performance for contaminants. Herein, using well facet-controlled I-Cu2WS4 single crystals as a model transition metal chalcogenide sorbent, we investigated the adsorption performance of the exposed facets toward gaseous elemental mercury (Hg0). We discovered that the decahedron exhibited not only facet-dependent adsorption properties for Hg0 but also recrystallization along the preferential [001] growth direction from a metastable state to the steady state. Besides, the metastable crystals with a predominant exposure of {101} facets dominated the promising adsorption efficiency (about 99% at 75 °C) while the saturated adsorption capacity was evaluated to be 2.35 mg·g-1. Subsequently, comprehensive characterizations and X-ray adsorption fine structure (XAFS), accompanied by density functional theory (DFT) calculations, revealed that it might be owing to the coordinatively unsaturated local environment of W atoms with S defects and the surface relative stability of different facets, which could be affected by the change in surface atom configuration. Hence, the new insight into the facet-dependent adsorption property of transition metal chalcogenide for Hg0 may have important implications, and the atomic-level study directly provides instructions for development and design of highly efficient functional materials.

10.
J Am Chem Soc ; 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33719415

RESUMEN

In organic photovoltaic (OPV) blends, photogenerated excitons dissociate into charge-separated electrons and holes at donor/acceptor interfaces. The bimolecular recombination of spin-uncorrelated electrons and holes may cause nonradiative loss by forming the low-lying triplet excited states (T1) via the intermediate charge-transfer triplet states. Here, we show that such a spin-related loss channel can be suppressed in the OPV blends with fluorinated nonfullerene acceptors (NFAs). By combining ultrafast optical spectroscopy and triplet sensitization measurements, the T1 states at the acceptors have been observed to generate from the charge-separated electrons and holes in the OPV blends with a same polymer donor and two sets of NFAs with and without fluorination. The triplet formation is largely suppressed and the lifetime of charge carrier is markedly prolonged in the blends with fluorinated NFAs. The fluorination effect on the charge dynamics can be ascribed to the modified energy alignment between the triplet excited states of charge-transfer and locally excited characters as supported by quantum chemical computation. Our findings explain the mechanism responsible for the improved photocurrent generation in the OPV blends with fluorinated NFAs, suggesting that manipulating the energy landscape of triplet excited states is a promising strategy for further optimizing OPV devices.

11.
J Chromatogr Sci ; 2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33667297

RESUMEN

Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC-MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose-response for quantification was observed over the range of 10-5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87-102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at -80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.

12.
Emerg Microbes Infect ; 10(1): 619-628, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33682641

RESUMEN

Enterovirus A71 (EV-A71) inactivated vaccines have been widely inoculated among children in Kunming City after it was approved. However, there was a large-scale outbreak of Enteroviruses (EVs) infection in Kunming, 2018. The epidemiological characteristics of HFMD and EVs were analysed during 2008-2018, which are before and three years after EV-A71 vaccine starting to use. The changes in infection spectrum were also investigated, especially for severe HFMD in 2018. The incidence of EV-A71 decreased dramatically after the EV-A71 vaccine starting use. The proportion of non-CV-A16/EV-A71 EVs positive patients raised to 77.17-85.82%, while, EV-A71 and CV-A16 only accounted for 3.41-7.24% and 6.94-19.42% in 2017 and 2018, respectively. CV-A6 was the most important causative agent in all clinical symptoms (severe HFMD, HFMD, Herpangina and fever), accounting from 42.13% to 62.33%. EV-A71 only account for 0.36-2.05%. In severe HFMD, CV-A6 (62.33%), CV-A10 (11.64%), and CV-A16 (10.96%) were the major causative agent in 2018. EV-A71 inactivated vaccine has a good protective effect against EV-A71 and induced EVs infection spectrum changefully. EV-A71 vaccine has no or insignificant cross-protection effect on CV-A6, CV-A10, and CV-A16. Herein, developing 4-valent combined vaccines is urgently needed.

13.
Hepatology ; 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33710653

RESUMEN

Chronic alcohol drinking is a major risk factor for alcohol-associated liver disease (ALD). FK506-binding protein 51 (FKBP5), a co-chaperone protein, is involved in many key regulatory pathways. It is known to be involved in stress-related disorders but there are no reports regarding its role in ALD. This present study aimed to examine the molecular mechanism of FKBP5 in ALD. We found a significant increase in hepatic FKBP5 transcripts and protein expression in patients with ALD and mice fed with chronic-plus-single binge ethanol. Loss of Fkbp5 in mice protected against alcohol-induced hepatic steatosis and inflammation. Transcriptomic analysis revealed a significant reduction of Tead1 and Cxcl1 mRNA in ethanol-fed Fkbp5-/- mice. Ethanol-induced Fkbp5 expression was secondary to downregulation of methylation level at its 5' UTR promoter region. The increase in Fkbp5 expression led to induction in transcription factor Tead1 through Hippo signaling pathway. Fkbp5 can interact with YAP upstream kinase, MST1, affecting its ability to phosphorylate YAP and the inhibitory effect of hepatic YAP phosphorylation by ethanol leading to YAP nuclear translocation and TEAD1 activation. Activation of TEAD1 led to increased expression of its novel target, CXCL1, a chemokine-mediated neutrophil recruitment, causing hepatic inflammation and neutrophil infiltration in our mouse model. CONCLUSION: We identified a novel FKBP5-YAP-TEAD1-CXCL1 axis in the pathogenesis of ALD. Loss of FKBP5 ameliorates alcohol-induced liver injury through the Hippo pathway and CXCL1 signaling, suggesting its potential role as a target for the treatment of ALD.

14.
Chin Med J (Engl) ; 134(5): 524-531, 2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33652458

RESUMEN

BACKGROUND: Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China. METHODS: We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI. RESULTS: The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84-0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17-0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33-5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01-1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48-17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals. CONCLUSIONS: Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.

15.
Leukemia ; 2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731850

RESUMEN

Pediatric myelodysplastic syndromes (MDS) are a heterogeneous disease group associated with impaired hematopoiesis, bone marrow hypocellularity, and frequently have deletions involving chromosome 7 (monosomy 7). We and others recently identified heterozygous germline mutations in SAMD9 and SAMD9L in children with monosomy 7 and MDS. We previously demonstrated an antiproliferative effect of these gene products in non-hematopoietic cells, which was exacerbated by their patient-associated mutations. Here, we used a lentiviral overexpression approach to assess the functional impact and underlying cellular processes of wild-type and mutant SAMD9 or SAMD9L in primary mouse or human hematopoietic stem and progenitor cells (HSPC). Using a combination of protein interactome analyses, transcriptional profiling, and functional validation, we show that SAMD9 and SAMD9L are multifunctional proteins that cause profound alterations in cell cycle, cell proliferation, and protein translation in HSPCs. Importantly, our molecular and functional studies also demonstrated that expression of these genes and their mutations leads to a cellular environment that promotes DNA damage repair defects and ultimately apoptosis in hematopoietic cells. This study provides novel functional insights into SAMD9 and SAMD9L and how their mutations can potentially alter hematopoietic function and lead to bone marrow hypocellularity, a hallmark of pediatric MDS.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33738732

RESUMEN

The instant endeavor was undertaken for determination of lead (Pb) in water, soil, forage, and cow's blood domesticated in contaminated area of heavy automobiles' exhaust in Sahiwal town of District Sargodha, Pakistan. Water samples showed that the concentration of Pb ranged from 1.14 to 0.44 mg kg-1 at all sites. It was maximum at site 5 and minimum at site 2. Soil samples showed the concentration of Pb at all sites ranged from 1.58 to 0.279 mg kg-1. It was maximum in soil where Avena sativa was grown at site 5 and was found minimum in soil where Zea mays was grown at site 2. While among samples of forage, the concentration of Pb ranges from 0.048 to 2.002 mg kg-1. The highest Pb amount was found in Brassica campestris at site 1 and the minimum was recorded in Trifolium alexandrinum at site 2. Finally, the blood samples of cow depicted that concentration of Pb ranged from 4.468 to 0.217 mg kg-1. It was the maximum at site 1 and the minimum at site 3. It is recommended that such study should be conducted in other districts for public awareness.

17.
Cancer Med ; 10(7): 2509-2522, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33704935

RESUMEN

Prostate cancer-associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes, has been reported to have anti-tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS-treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS-treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3-100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC-3 cells, while that of MPSSS-treated prostate CAFs (MT-lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT-lmwCAFS to identify functional molecules that inhibit the growth of PC-3 cells, and proteomic analysis of lmwCAFS-treated PC-3 cells and MT-lmwCAFS-treated PC-3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF-ß3 from MT-lmwCAFS may inhibit the growth of PC-3 cells. The validated experiments revealed that TGF-ß3 from MT-lmwCAFS activated p21 expression in PC-3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC-3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC-3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression.

18.
Commun Biol ; 4(1): 402, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33767359

RESUMEN

Osteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

19.
BMC Pulm Med ; 21(1): 91, 2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731064

RESUMEN

BACKGROUND: Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. METHODS: Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case-control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored. RESULTS: Twenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. L-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis. CONCLUSIONS: Distinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. L-arginine and kynurenine were correlated with the severity of silicosis.

20.
J Ethnopharmacol ; 274: 114051, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33746001

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia mussotii Franch (SMF) is a well-known Tibetan medicine for the treatment of liver disease in China. However, the chemical profile and molecular mechanism of SMF against hepatic fibrosis are not yet well explored. AIM OF THE STUDY: This work aimed to elucidate the chemical profile of SMF and investigate the action mechanisms of SMF against carbon tetrachloride (CCl4)-induced hepatic fibrosis. MATERIALS AND METHODS: Ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOFMS) and UNIFI platform was firstly employed to reveal the chemical profile of SMF. Cross-platform serum metabolomics based on gas chromatography/liquid chromatography-mass spectrometry were performed to characterize the metabolic fluctuations associated with CCl4-induced hepatic fibrosis in mice and elucidate the underlying mechanisms of SMF. Western blotting was further applied to validate the key metabolic pathways. RESULTS: A total of 31 compounds were identified or tentatively characterized from SMF. Twenty-seven differential metabolites were identified related with CCl4-induced liver fibrosis, and SMF could significantly reverse the abnormalities of seventeen metabolites. The SMF-reversed metabolites were involved in arachidonic acid metabolism, glycine, serine and threonine metabolism, tyrosine metabolism, arginine and proline metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and TCA cycle. The results of western blotting analysis showed that SMF could alleviate liver fibrosis by increasing the levels of CYP7A1, CYP27A1 and CYP8B1 and decreasing the level of LPCAT1 to regulate the metabolic disorders of primary bile acid biosynthesis and glycerophospholipid. CONCLUSION: It could be concluded that primary bile acid biosynthesis and glycerophospholipid metabolism were the two important target pathways for SMF-against liver fibrosis, which provided the theoretical foundation for its clinical use.

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