Publications by authors named "Li Chen"

6,798 Publications

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PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus.

Nat Commun 2021 May 14;12(1):2829. Epub 2021 May 14.

Center of Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Polycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.
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http://dx.doi.org/10.1038/s41467-021-22871-0DOI Listing
May 2021

Hybrid Face Reflectance, Illumination, and Shape from a Single Image.

IEEE Trans Pattern Anal Mach Intell 2021 May 14;PP. Epub 2021 May 14.

We propose HyFRIS-Net to jointly estimate the hybrid reflectance and illumination models, as well as the refined face shape from a single unconstrained face image in a pre-defined texture space. The proposed hybrid reflectance and illumination representation ensure photometric face appearance modeling in both parametric and non-parametric spaces for efficient learning. While forcing the reflectance consistency constraint for the same person and face identity constraint for different persons, our approach recovers an occlusion-free face albedo with disambiguated color from the illumination color. Our network is trained in a self-evolving manner to achieve general applicability on real-world data. We conduct comprehensive qualitative and quantitative evaluations with state-of-the-art methods to demonstrate the advantages of HyFRIS-Net in modeling of photo-realistic face albedo, illumination, and shape.
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http://dx.doi.org/10.1109/TPAMI.2021.3080586DOI Listing
May 2021

Comprehensive Understanding of the Relationship between Bioactive Compounds of Black Tea and its Angiotensin Converting Enzyme (ACE) Inhibition and Antioxidant Activity.

Plant Foods Hum Nutr 2021 May 14. Epub 2021 May 14.

College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

Long term regular intake of black tea (BT) can lower blood pressure, which is probably due to its antioxidant activity and angiotensin converting enzymes (ACE) inhibitory activity. This study achieves a comprehensive understanding of the relationship between bioactive compounds of BT and its ACE inhibitory activity and antioxidant activity. Phenolic compounds are closely related to antioxidant activity and ACE inhibitory activity. Catechin (C) exhibits stronger inhibitory activity on ACE enzyme than that of other compounds. Molecular docking demonstrates that C could directly bind to ACE active site pockets and Zn(II). Other bioactive compounds are involved in antioxidant and ACE inhibitory activity in varying degrees but no obvious trend is established. Our study proposes a conjecture that some bioactive compounds of BT regulate antioxidant defenses through mechanisms that involve ACE. The mixed mode of in vitro inhibition of ACE and oxidant of BT bioactive compounds needs to be further investigated.
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http://dx.doi.org/10.1007/s11130-021-00896-6DOI Listing
May 2021

Handgrip and sex-specific cardiometabolic risk factors in Hispanic/Latino migrant farmworkers.

Sci Rep 2021 May 13;11(1):10272. Epub 2021 May 13.

Georgia Prevention Institute, Department of Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.

Studies have suggested that handgrip strength might be a marker for cardiometabolic risk (CMR), but it has not been studied in Hispanic/Latino farmworker population. This study aimed to characterize absolute and relative handgrip strength in Hispanic/Latino farmworkers, and investigate the sex-specific association between handgrip strength and CMR factors. CMR factors and seated isometric absolute (the sum of both hands) and relative (absolute handgrip strength divided by body mass index) handgrip strengths were collected in 173 Hispanic/Latino farmworkers (mean age 35.1 ± 0.7 years; 49% female). The absolute and the relative handgrip strengths were 89.2 ± 1.8 kg, 3.3 ± 0.1 kg among males, and 56.5 ± 1.9 kg, 1.9 ± 0.1 kg among females, respectively. Age was correlated with absolute (r = - 0.17, p = 0.03) and relative handgrip strengths (r = - 0.28, p < 0.01). In males, absolute handgrip was related to triglycerides (r = - 0.25, p < 0.05), whereas relative handgrip was related to waist circumference (r = - 0.32, p < 0.01), waist/hip circumference ratio (r = - 0.36, p < 0.01), high-density lipoprotein (r = 0.24, p < 0.05), and triglycerides (r = - 0.35, p < 0.01). In females, absolute handgrip was related to fasting plasma glucose (r = - 0.28, p = 0.03), whereas relative handgrip was related to waist circumference (r = - 0.38, p < 0.01) and fasting plasma glucose (r = - 0.22, p < 0.05). Males had lower absolute handgrip strength when their triglycerides levels were at risk (p = 0.021), and lower relative handgrip strength when their plasma glucose (p = 0.034) and triglycerides (p = 0.002) levels were at risk. Females had lower relative handgrip strength when their plasma glucose (p = 0.001) and blood pressure (p = 0.004) were at risk. This study suggests that handgrip strength may be associated with sex-specific CMR factors in a Hispanic/Latino farmworker population.
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http://dx.doi.org/10.1038/s41598-021-89138-yDOI Listing
May 2021

Temporal characterization of heating in femtosecond laser filamentation with planar Rayleigh scattering.

Opt Express 2021 May;29(10):14883-14893

Temporal and spatial evolution of temperature in femtosecond laser filamentation is investigated using planar Rayleigh scattering combined with optical flow algorithm, the corresponding mechanism is analyzed. The temperature increases sharply with a characteristic time of 4.53μs and reach a maximum value of 418 K within 1∼10μs, then decreases slowly to around 300 K with a characteristic time of 136μs. While the temperature first diffuses rapidly in the radial direction and then diffuses very slowly, an obvious step is observed around 2μs. The mechanism of heat transfer is the result of energy exchange between electron and heavy particles and heat conduction. Within 1 ns to 10μs, molecules obtain energy continuously due to collision with electrons, which is much larger than the energy loss due to thermal conduction, leading to rise of gas temperature and the high-speed movement of the filament edges. After 10μs, thermal conduction becomes the dominant factor, resulting gas temperature decreasing and slower movement of the filament edges.
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http://dx.doi.org/10.1364/OE.418654DOI Listing
May 2021

Effects of alkali, enzymes, and ultrasound on monosodium glutamate byproduct for a sustainable production of Bacillus subtilis.

Food Chem 2021 Apr 27;360:129967. Epub 2021 Apr 27.

Institute of Food Science and Technology, College of Biological Science and Engineering, Fuzhou University, 350108 Fuzhou, China; Fujian Center of Excellence for Food Biotechnology, 350108 Fuzhou, China.

Due to the hindrance of flocculated polymers and bacterial cell wall, the production of Bacillus subtilis using monosodium glutamate byproduct (MSGB) was low. With the assistance of scanning electron microscope images, effects of alkali, lysozyme, papain, ultrasound, and their combinations on MSGB were evaluated using the results of soluble protein, carbohydrate, monosaccharides and peptidoglycans. Alkali could dissolve flocculated polymers increasing 21% soluble MSGB, and thus enhanced the subsequent treatments (ultrasound, lysozyme, or papain) to increase 14-17% soluble MSGB. As ultrasound mainly released intercellular components (mannose, and glucose) while lysozyme or papain mainly released cell wall components (peptidoglycans), the combination of alkali, ultrasound, and enzymes led to a highest soluble MSGB (78%), yielding a maximal B. subtilis production of 6.6 × 10 colony-forming units mL. This yield was about 33 times that of using untreated MSGB, and the key to improve B. subtilis production was the release of carbohydrate.
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http://dx.doi.org/10.1016/j.foodchem.2021.129967DOI Listing
April 2021

Development of TACE Refractoriness Scores in Hepatocellular Carcinoma.

Front Mol Biosci 2021 26;8:615133. Epub 2021 Mar 26.

Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

To identify the independent risk factors for transarterial embolization (TACE) refractoriness and to develop a novel TACE refractoriness score and nomogram for predicting TACE refractoriness in patients with hepatocellular carcinoma (HCC). Between March 2006 and March 2016, HCC patients who underwent TACE monotherapy as initial treatment at two hospitals formed the study cohort and validation cohort. The criteria of TACE refractoriness followed the Japan Society of Hepatology 2014 version of TACE refractoriness. In the study cohort, the independent risk factors for TACE refractoriness were identified, and TACE refractoriness score and nomogram were then developed. The accuracy of the systems was validated externally in the validation cohort. In total, 113 patients from hospital A formed the study cohort and 122 patients from hospital B formed the validation cohort. In the study cohort, 82.3% of the patients ( = 93) developed TACE refractoriness with a median overall survival (OS) of 540 days (95% CI, 400.8-679.1), and the remaining 20 patients in the TACE-non-refractory group had a median OS of 1,257 days (95% CI, 338.8-2,175.2) ( = 0.019). The median time for developing TACE refractoriness was 207 days (95% CI, 134.8-279.2), and a median number of two TACE procedures were performed after refractoriness developed. The independent risk factors for TACE refractoriness were the number of tumors and bilobular invasion of HCC. TACE refractoriness scores <3.5 indicated a lower incidence of TACE refractoriness, whereas scores >3.5 points indicated a higher incidence ( < 0.001). In the validation cohort, 77.9% of the patients ( = 95) developed TACE refractoriness with a median OS of 568 days (95% CI, 416.3-719.7), and a median OS of 1,324 days was observed in the TACE-non-refractory group ( = 27; 95% CI, 183.5-2,464.5). TACE refractoriness impairs the OS of HCC patients. The number of tumors and bilobular invasion status were independent risk factors for TACE refractoriness. The TACE refractoriness score can be an effective tool and easy approach to predict the risk of TACE refractoriness status.
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http://dx.doi.org/10.3389/fmolb.2021.615133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109267PMC
March 2021

Polysaccharide Promotes Diabetic Wound Healing Through Inhibition of the NLRP3 Inflammasome.

Front Pharmacol 2021 26;12:659215. Epub 2021 Apr 26.

Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

The aim of this study was to evaluate the therapeutic effects of polysaccharide (BSP) on wound healing in diabetes mellitus (DM) and to explore the underlying mechanisms. DM mouse models were induced by high fat-diet feeding combined with low-dose streptozocin injection. To establish diabetic foot ulcer (DFU) models, DM mice were wounded on the dorsal surface. Subsequently, mice were treated with vehicle or BSP for 12 days and wound healing was monitored. The effects of BSP on the production of interleukin-1β (IL-1β), tumor necrosis factor-α, macrophages infiltration, angiogenesis, the activation of nucleotide-binding and oligomerization (NACHT) domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome, and insulin sensitivity in wound tissues were subsequently evaluated. Separated- and cultured- bone marrow-derived macrophages (BMDMs) and cardiac microvascular endothelial cells (CMECs) were isolated from mice and used to investigate the effects of BSP on cell viability, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation and insulin sensitivity following exposure to high glucose (HG). BSP administration accelerated diabetic wound healing, suppressed macrophage infiltration, promoted angiogenesis, suppressed NLRP3 inflammasome activation, decreased IL-1β secretion, and improved insulin sensitivity in wound tissues in DM mice. , co-treatment with BSP protected against HG-induced ROS generation, NLRP3 inflammasome activation, and IL-1β secretion in BMDMs, and improved cell viability and decreased ROS levels in CMECs. Moreover, in HG exposed BMDMs-CMECs cultures, BSP treatment suppressed NLRP3 inflammasome activation and IL-1β secretion in BMDMs, and improved cell viability and insulin sensitivity in CMECs. Furthermore, treatment with IL-1β almost completely suppressed the beneficial effects of BSP on the NLRP3 inflammasome, IL-1β secretion, and insulin sensitivity in HG-treated BMDMs-CMECs. BSP promotes DFU healing through inhibition of the HG-activated NLRP3 inflammasome.
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http://dx.doi.org/10.3389/fphar.2021.659215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110216PMC
April 2021

EMDS-5: Environmental Microorganism image dataset Fifth Version for multiple image analysis tasks.

PLoS One 2021 12;16(5):e0250631. Epub 2021 May 12.

School of Control Engineering, Chengdu University of Information Technology, Chengdu, China.

Environmental Microorganism Data Set Fifth Version (EMDS-5) is a microscopic image dataset including original Environmental Microorganism (EM) images and two sets of Ground Truth (GT) images. The GT image sets include a single-object GT image set and a multi-object GT image set. EMDS-5 has 21 types of EMs, each of which contains 20 original EM images, 20 single-object GT images and 20 multi-object GT images. EMDS-5 can realize to evaluate image preprocessing, image segmentation, feature extraction, image classification and image retrieval functions. In order to prove the effectiveness of EMDS-5, for each function, we select the most representative algorithms and price indicators for testing and evaluation. The image preprocessing functions contain two parts: image denoising and image edge detection. Image denoising uses nine kinds of filters to denoise 13 kinds of noises, respectively. In the aspect of edge detection, six edge detection operators are used to detect the edges of the images, and two evaluation indicators, peak-signal to noise ratio and mean structural similarity, are used for evaluation. Image segmentation includes single-object image segmentation and multi-object image segmentation. Six methods are used for single-object image segmentation, while k-means and U-net are used for multi-object segmentation. We extract nine features from the images in EMDS-5 and use the Support Vector Machine (SVM) classifier for testing. In terms of image classification, we select the VGG16 feature to test SVM, k-Nearest Neighbors, Random Forests. We test two types of retrieval approaches: texture feature retrieval and deep learning feature retrieval. We select the last layer of features of VGG16 network and ResNet50 network as feature vectors. We use mean average precision as the evaluation index for retrieval. EMDS-5 is available at the URL:https://github.com/NEUZihan/EMDS-5.git.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250631PLOS
May 2021

Preeclampsia and Its Complications Exacerbate Development of Postpartum Depression: A Retrospective Cohort Study.

Biomed Res Int 2021 22;2021:6641510. Epub 2021 Apr 22.

The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Background: Hypertensive disorders were proved to be associated with the development of depression. But it is unclear if pregnancy-induced hypertensive diseases, especially preeclampsia (PE), will affect postpartum moods. We aimed to determine the incidence rate of postpartum depression (PPD) in PE patients and comprehensively evaluate the association between PPD and PE, including its severity and complications.

Methods: 425 participants including 130 PE mothers were enrolled in this retrospective cohort study. Each woman was asked to complete a questionnaire integrating the Edinburgh Postnatal Depression Scale (EPDS), the Leakage Index Questionnaire, and a pain scale questionnaire within 6 weeks after delivery. The EPDS cut-off score above 13 was recognized as screening positive for PPD. Data between groups were compared by bivariate analysis.

Results: PE mothers showed a direct tendency to PPD development. The positive screening for PPD in the PE group was significantly higher than that of the control group (30.77% vs. 14.58%). Based on the results of the regression model, women diagnosed with severe PE and fetal growth restriction were more inclined to develop PPD than normal ones (AOR: 2.759, 95% CI: 1.206-6.315 and AOR: 3.450, 95% CI: 1.596-7.458). It is also indicated that postpartum pain exacerbated the odds of PPD in PE patients (AOR: 1.509, 95% CI: 1.078-2.114).

Conclusions: PE was an independent risk factor for PPD. Its severity and complications exacerbate the development of PPD. Doctors and society should pay more attention to PE patients after delivery against the development of PPD.
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http://dx.doi.org/10.1155/2021/6641510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087462PMC
April 2021

Isolation and characterization of a novel Lactobacillus plantarum MMB-07 from traditional Suanyu for Acanthogobius hasta fermentation.

J Biosci Bioeng 2021 May 7. Epub 2021 May 7.

Department of Chemical and Environmental Engineering, University of Nottingham Malaysia, Jalan Broga, Semenyih, 43500 Selangor, Malaysia. Electronic address:

As one of Lianyungang's most famous specialties, Acanthogobius hasta is delicious and nutritious fish, but is extremely susceptible to spoilage during transportation and storage. In this study, Lactobacillus plantarum MMB-07 was isolated from traditional fermented sour fish to reduce losses and improve the utilization and food value of A. hasta. L. plantarum MMB-07 had good ability of acid production and acid resistance. Moreover, it could also inhibit common pathogens in food or aquatic products to ensure the safety of fermented products. MMB-07 was used to ferment A. hasta and obtain fermented Suanyu rich in nutrition value and good flavor. The volatile base nitrogen was 18.44 mg/100 g and the fermented fish meat maintained second-grade freshness. Thiobarbituric acid assay was 0.90 mg/kg and fat in fish meat was oxidized to a low degree. The studies indicated that MMB-07 has a high application prospect in low salt fermented fish.
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http://dx.doi.org/10.1016/j.jbiosc.2020.12.016DOI Listing
May 2021

The effect of recombinant human interferon alpha nasal drops to prevent COVID-19 pneumonia for medical staff in an epidemic area.

Curr Top Med Chem 2021 Apr 28. Epub 2021 Apr 28.

Novel Coronavirus Pneumonia Prevention and Control Team, Taihe Hospital, Hubei University of Medicine. 442000, Shiyan, Hubei, China.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known as Coronavirus disease-2019 (COVID-19) has caused the sixth world public health emergency. Healthcare staff as frontline population fighting the pandemic are exposed to high risk of infection. Therefore, developing protective intervention for medical staff is of significant importance.

Objective: To explore the effectiveness and safety of recombinant human interferon alpha (rhIFN-α) nasal drops for the prevention of coronavirus disease 2019 (COVID-19) through administering it to medical staff.

Method: This was a prospective open-label clinical trial with parallel intervention assignment conducted on 2944 medical staff including both doctors and nurses from Taihe Hospital, Shiyan City, Hubei Province, China from January 21, 2020 to July 30, 2020. The participants were bifurcated into two groups of low risk and high risk groups according to the level of direct exposure to COVID-19 patients. The individuals of the low-risk group received rhIFN-α nasal drops for one month in addition to first level protection, and the high-risk group received a combination of rhIFN-α nasal drops coupled with thymosin-α1 with either second or third-level protection protocol. Moreover, the new-outset of COVID-19 pneumonia diagnosed by chest computed tomography (CT), after thirty days was the primary outcome. The adverse reactions were recorded in all participants.

Results: Two thousand and four hundred fifteen of 2944 individuals belonged to the low-risk group, while 529 to the high-risk group. There was no COVID-19 pneumonia in either of the group after thirty days. The pulmonary CT scans were negative for COVID-19 pneumonia in both the groups with no new clinical symptoms. No serious adverse event was observed during the course of the intervention.

Conclusion: The rhIFN-α nasal drops along with augmented safeguard based on standard physical isolation could effectively protect medical staff against COVID-19 pneumonia.
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http://dx.doi.org/10.2174/1568026621666210429083050DOI Listing
April 2021

Comparison of Two Major Staging Systems in Predicting Survival and Recommendation of Postoperative Radiotherapy Based on the 11th Japanese Classification for Esophageal Carcinoma After Curative Resection: A Propensity Score-Matched Analysis.

Ann Surg Oncol 2021 May 9. Epub 2021 May 9.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: The aim of this study was to compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) staging system with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on a substage of the JES staging system.

Methods: Area under the curve (AUC) values of the receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus PORT [S+RT group]) across substages of the 11th JES staging system according to independent prognostic factors for overall survival (OS) identified using Cox proportional hazards regression.

Results: A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC staging system was significantly higher than that for the 11th JES staging system (0.701 vs. 0.675, p < 0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (p < 0.001) and 21.1% (p < 0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; p < 0.001).

Conclusion: The 11th JES staging system was less capable of predicting prognosis than the 8th AJCC staging system and patients in stage III of the JES staging system were highly recommended to undergo PORT.
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http://dx.doi.org/10.1245/s10434-021-10046-6DOI Listing
May 2021

Corrigendum: LncRNA PCAT6 Induces M2 Polarization of Macrophages in Cholangiocarcinoma via Modulating miR-326 and RhoA-ROCK Signaling Pathway.

Front Oncol 2021 22;11:680500. Epub 2021 Apr 22.

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.

[This corrects the article DOI: 10.3389/fonc.2020.605877.].
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http://dx.doi.org/10.3389/fonc.2021.680500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100825PMC
April 2021

How Exercise Protects Against Mild Cognitive Impairment in Nursing Home-Dwelling Older Adults: A Path Analysis.

J Nerv Ment Dis 2021 May 6. Epub 2021 May 6.

School of Nursing, Jilin University, Changchun, Jilin, China.

Abstract: To explore how exercise protects against mild cognitive impairment (MCI) from physical, psychological, and social perspectives, we conducted a cross-sectional study in four nursing homes in Changchun, China, selected by convenience sampling. A total of 338 older adults aged 60 years or more with normal cognition or MCI were included. Data including demographic characteristics, exercise habits, frailty status, depression, sleep quality, social support, and cognitive status were collected. Weighted least squares estimation with mean and variance adjusted chi-square and bootstrapping with 2000 resamples were used to conduct the analyses through Mplus 8.3. The results showed that both direct and indirect effects of exercise on MCI were significant. Frailty and depression were two independent mediating factors, and depression could also play a mediating role when combined with sleep quality or frailty. Social support played a partial mediating role between exercise and depression. Formulations of exercise programs for MCI prevention and improvement in nursing home-dwelling older adults should consider the mediating factors.
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http://dx.doi.org/10.1097/NMD.0000000000001361DOI Listing
May 2021

The paraventricular thalamus input to central amygdala controls depression-related behaviors.

Exp Neurol 2021 May 6:113744. Epub 2021 May 6.

Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong, China. Electronic address:

The dysregulation of neuronal networks may contribute to the etiology of major depressive disorder (MDD). However, the neural connections underlying the symptoms of MDD have yet to be elucidated. Here, we observed that glutamatergic neurons in the paraventricular thalamus (PVT) were activated by chronic unpredictable stress (CUS) with higher expression numbers of ΔFosB-labeled neurons and protein expression levels, activation of PVT neurons caused depressive-like phenotypes, whereas suppression of PVT neuronal activity induced an antidepressant effect in male, but not female mice, which were achieved by using a chemogenetic approach. Moreover, we found that PVT glutamatergic neurons showed strong neuronal projections to the central amygdala (CeA), activation of the CeA-projecting neurons in PVT or the neuronal terminals of PVT-CeA projection neurons induced depression-related behaviors or showed enhanced stress-induced susceptibility. These results suggest that PVT is a key depression-controlling nucleus, and PVT-CeA projection regulates depression-related behaviors in a sex-dependent manner, which could be served as an essential pathway for morbidity and treatment of depression.
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http://dx.doi.org/10.1016/j.expneurol.2021.113744DOI Listing
May 2021

Application of a classifier combining bronchial transcriptomics and chest CT features facilitates the diagnostic evaluation of lung cancer in smokers and non-smokers.

Int J Cancer 2021 May 8. Epub 2021 May 8.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Lung cancer screening by computed tomography (CT) reduces mortality but exhibited high false-positive rates. We established a diagnostic classifier combining chest CT features with bronchial transcriptomics. Patients with CT-detected suspected lung cancer were enrolled. The sample collected by bronchial brushing was used for RNA sequencing. The e1071 and pROC packages in R software was applied to build the model. Eventually, a total of 283 patients, including 183 with lung cancer and 100 with benign lesions, were included into final analysis. When incorporating transcriptomic data with radiological characteristics, the advanced model yielded 0.903 AUC with 81.1% NPV. Moreover, the classifier performed well regardless of lesion size, location, stage, histologic type, or smoking status. Pathway analysis showed enhanced epithelial differentiation, tumor metastasis, and impaired immunity were predominant in smokers with cancer, whereas tumorigenesis played a central role in non-smokers with cancer. Apoptosis and oxidative stress contributed critically in metastatic lung cancer; by contrast, immune dysfunction was pivotal in locally advanced lung cancer. Collectively, we devised a minimal-to-noninvasive, efficient diagnostic classifier for smokers and non-smokers with lung cancer, which provides evidence for different mechanisms of cancer development and metastasis associated with smoking. A negative classifier result will help the physician make conservative diagnostic decisions.
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http://dx.doi.org/10.1002/ijc.33675DOI Listing
May 2021

Carbon monoxide alleviates senescence in diabetic nephropathy by improving autophagy.

Cell Prolif 2021 May 7:e13052. Epub 2021 May 7.

Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Laboratory of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: Senescence, characterized by permanent cycle arrest, plays an important role in diabetic nephropathy (DN). However, the mechanism of renal senescence is still unclear, and the treatment targeting it remains to be further explored.

Materials And Methods: The DN mice were induced by HFD and STZ, and 3 types of renal cells were treated with high glucose (HG) to establish in vitro model. Senescence-related and autophagy-related markers were detected by qRT-PCR and Western blot. Further, autophagy inhibitors and co-immunoprecipitation were used to clarify the mechanism of CO. Additionally, the specific relationship between autophagy and senescence was explored by immunofluorescence triple co-localization and ELISA.

Results: We unravelled that senescence occurred in vivo and in vitro, which could be reversed by CO. Mechanistically, we demonstrated that CO inhibited the dysfunction of autophagy in DN mice partly through dissociating Beclin-1-Bcl-2 complex. Further results showed that autophagy inhibitors blocked the improvement of CO on senescence. In addition, the data revealed that autophagy regulated the degradation of senescence-related secretory phenotype (SASP) including Il-1β, Il-6, Tgf-β and Vegf.

Conclusions: These results suggested that CO protects DN mice from renal senescence and function loss via improving autophagy partly mediated by dissociating Beclin-1-Bcl-2 complex, which is possibly ascribed to the degradation of SASP. These findings bring new ideas for the prevention and treatment of DN and the regulation of senescence.
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http://dx.doi.org/10.1111/cpr.13052DOI Listing
May 2021

Impact of beta-2 microglobulin expression on the survival of glioma patients via modulating the tumor immune microenvironment.

CNS Neurosci Ther 2021 May 7. Epub 2021 May 7.

Brain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Aims: High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta-2 microglobulin (B2M) in lower-grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration.

Methods: A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan-Meier survival analysis and meta-analysis were used for survival analysis. GO(Gene-ontology) enrichment analysis, co-expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma.

Results: We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta-analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co-expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines.

Conclusions: We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.
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http://dx.doi.org/10.1111/cns.13649DOI Listing
May 2021

Modulating surface charge of dexamethasone non-spherical microcrystals for improved inner ear delivery.

Colloids Surf B Biointerfaces 2021 Apr 29;204:111806. Epub 2021 Apr 29.

Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China. Electronic address:

It is important to achieve precise surface charge manipulation of non-spherical drug microcrystals using facile and time-efficient methods for local drug delivery. In this study, silk-coated dexamethasone (DEX) non-spherical microcrystals were synthesized by precipitation technique followed by alternate deposition of poly(allylamine hydrochloride) (PAH) (or PAH-coated FeO) and silk fibroin (SF) via layer-by-layer assembly. EDC and glutaraldehyde were employed to manipulate positive or negative charge of particles by simple chemical cross-linking reactions, respectively. In vivo assessment was carried out by intratympanic (IT) injection of DEX non-spherical microcrystals in guinea pigs. In vivo pharmacokinetic results demonstrate that negatively charged DEX microcrystals appeared to improve outcomes of inner ear delivery in comparison to positively-charged counterparts. This is partly because of the adhesive features of the SF. The present study may provide new ideas to construct surface charge-tunable drug delivery vehicles that are capable of crossing biological barriers, especially for inner ear delivery due to the simple and practical strategy.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111806DOI Listing
April 2021

Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype.

Can J Gastroenterol Hepatol 2021 12;2021:6610434. Epub 2021 Apr 12.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs 31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp.
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http://dx.doi.org/10.1155/2021/6610434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057911PMC
April 2021

The prevalence of fatigue among Chinese nursing students in post-COVID-19 era.

PeerJ 2021 13;9:e11154. Epub 2021 Apr 13.

Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.

Background: Due to the COVID-19 outbreak, all teaching activities in nursing schools were suspended in China, and many nursing students were summoned to work in hospitals to compensate for the shortage of manpower. This study examined the prevalence of fatigue and its association with quality of life (QOL) among nursing students during the post-COVID-19 era in China.

Methods: This was a multicenter, cross-sectional study. Nursing students in five Chinese universities were invited to participate. Fatigue, depressive and anxiety symptoms, pain and QOL were measured using standardized instruments.

Results: A total of 1,070 nursing students participated. The prevalence of fatigue was 67.3% (95% CI [64.4-70.0]). Multiple logistic regression analysis revealed that male gender ( = 0.003, OR = 1.73, 95% CI [1.20-2.49]), and being a senior nursing student (second year: OR = 2.20, 95% CI [1.46-3.33], < 0.001; third year: OR = 3.53, 95% CI [2.31-5.41], < 0.001; and fourth year OR = 3.59, 95% CI [2.39-5.40], < 0.001) were significantly associated with more severe fatigue. In addition, moderate economic loss during the COVID-19 pandemic (OR = 1.48, 95% CI [1.08-3.33], < 0.015; compared to low loss), participants with more severe depressive (OR = 1.48, 95% CI [1.22-1.78], < 0.001) and anxiety symptoms (OR = 1.12, 95% CI [1.05-1.20], = 0.001), and more severe pain (OR = 1.67, 95%CI [1.46-1.91], < 0.001) were significantly associated with reported more severe fatigue. After controlling for covariates, nursing students with fatigue had a lower overall QOL score compared to those without ( = 31.4, < 0.001).

Conclusion: Fatigue was common among nursing students in the post-COVID-19 era. Considering the negative impact of fatigue on QOL and daily functioning, routine physical and mental health screening should be conducted for nursing students. Effective stress-reduction measures should be enforced to assist this subpopulation to combat fatigue and restore optimal health.
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http://dx.doi.org/10.7717/peerj.11154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051357PMC
April 2021

Rapid characterization and pharmacokinetic study of aristolochic acid analogues using ion mobility mass spectrometry.

Anal Bioanal Chem 2021 May 5. Epub 2021 May 5.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

Aristolochic acid analogues (AAAs), naturally existing in herbal Aristolochia and Asarum genera, were once widely used in traditional pharmacopeias because of their anti-inflammatory properties, but lately they were identified as potential nephrotoxins and mutagens. A method for rapid characterization of AAAs in serum was developed using ion mobility spectrometry coupled with mass spectrometry (IMS-MS). Five AAAs, containing four aristolochic acids and one aristolactam, were separated and identified within milliseconds. AAAs were separated in gas phase based on the difference of their ion mobility (K), and then identified based on their K values, m/z, and product ions from MS/MS. Quantitative analysis of AAAs was performed using an internal standard with a satisfactory sensitivity. Limits of detection (signal-to-noise = 3) and quantification (signal-to-noise = 10) were 1-5 ng/mL and 3-8 ng/mL, respectively. The method was validated and successfully applied to the pharmacokinetics study of AAAs in rats, offering a promising way for fast screening and evaluation of AAAs in biological samples.
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http://dx.doi.org/10.1007/s00216-021-03371-yDOI Listing
May 2021

Direct -alkylation of sulfur-containing amines.

Org Biomol Chem 2021 May 5. Epub 2021 May 5.

Catalytic Hydrogenation Research Center, State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310014, China.

An efficient ruthenium-catalyzed method has been developed for the direct N-alkylation of sulfur-containing amines with alcohols, for the first time, by a step-economical and environmentally friendly hydrogen borrowing strategy. The present methodology features base-free conditions and broad substrate scope, with water being the only by-product. Moreover, this protocol has been applied to the synthesis of the pharmaceutical drug Quetiapine.
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http://dx.doi.org/10.1039/d1ob00368bDOI Listing
May 2021

Mechanism of action of strychni semen for treating Rheumatoid arthritis and methods for attenuating the toxicity.

Comb Chem High Throughput Screen 2021 May 3. Epub 2021 May 3.

Department of Science and Education, Shandong Provincial Third Hospital, 250031, China.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which destructs joints and causes significant pain, impairing a patient's quality of life. Strychni semen showed promising results in treating RA. However, there are increasing safety concerns in using Strychni Semen due to its severe toxicity.

Aim And Objective: The purpose of this review is to provide insight into using Strychni Semen as an alternative medicine to treat RA, as well as to offer a method for the safe application of Strychni Semen through processing and compatibility studies.

Methods: Publications were retrieved and surveyed from CNKI and PubMed relevant to Strychni Semen for a literature review.

Results: This article summarized the mechanism of function of strychni semen in treating RA with its anti-inflammatory, analgesic, and immunomodulatory effect. Commonly used methods to attenuate the toxicity of strychni semen were also discussed in this article.

Conclusion: Strychni semen has a good therapeutic effect on RA, mainly by the modulation of immunity with anti-inflammatory and analgesic effects. Also, the reported toxicity of strychni semen can be effectively reduced by processing and reasonable compatibility. Hence, as an alternative medicine for RA treatment, strychni semen has a broad prospect.
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http://dx.doi.org/10.2174/1386207324666210504095523DOI Listing
May 2021

Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis.

Thorac Cancer 2021 May 5. Epub 2021 May 5.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT).

Methods: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward.

Results: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS.

Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.
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http://dx.doi.org/10.1111/1759-7714.13971DOI Listing
May 2021

Turn-on fluorescent probe for lipid droplet specific imaging of fatty liver and atherosclerosis.

J Mater Chem B 2021 May 5. Epub 2021 May 5.

National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.

Fluorescence imaging plays an important role in researching the biological function of lipid droplets (LDs). However, the short-wave emission, tedious synthesis process and insufficient specificity have significantly limited the applications of commercially available probes. Herein, we have prepared a novel one-step synthesized near-infrared (NIR) fluorescent probe, TNBD, with a very low emission in aqueous solution and the solid state, but a significantly enhanced fluorescence emission is exhibited in oleic acid. Moreover, TNBD exhibited an impressive lipid droplet (LD) specific fluorescence turn-on ability in cells, fatty liver and atherosclerosis (AS) samples with a good biocompatibility and high signal-to-noise ratio. Our study not only establishes a novel LD turn-on fluorescence probe, but also provides a novel way to prepare a NIR LD targeted fluorescence probe.
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http://dx.doi.org/10.1039/d1tb00335fDOI Listing
May 2021

Activating transcription factor 4 regulates angiogenesis under lipid overload via methionine adenosyltransferase 2A-mediated endothelial epigenetic alteration.

FASEB J 2021 Jun;35(6):e21612

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, P.R. China.

Lipid overload is intimately connected with the change of endothelial epigenetic status which impacts cellular signaling activities and endothelial function. Activating transcription factor 4 (ATF4) is involved in the regulation of lipid metabolism and meanwhile an epigenetic modifier. However, the role of ATF4 in the angiogenesis under lipid overload is not well understood. Here, to induce lipid overload status, we employed high-fat diet (HFD)-induced obese mouse model in vivo and palmitic acid (PA) to stimulate endothelial cells in vitro. Compared with mice fed with normal chow diet (NCD), HFD-induced obese mice showed angiogenic defects evidenced by decline in (1) blood flow recovery after hind limb ischemia, (2) wound healing speed after skin injury, (3) capillary density in injured tissues and matrigel plugs, and (4) endothelial sprouts of aortic ring. ATF4 deficiency aggravated above angiogenic defects in mice while ATF4 overexpression improved the blunted angiogenic response. Mechanistically, lipid overload lowered the H3K4 methylation levels at the regulatory regions of NOS3 and ERK1 genes, leading to reduced angiogenic signaling activity. Methionine adenosyltransferase 2A (MAT2A) is identified as a target of ATF4 and formed complex with ATF4 to direct lysine methyltransferase 2A (MLL1) to the regulatory regions of both genes for the maintenance of the H3K4 methylation level and angiogenic signaling activity. Here, we uncovered a novel metabolic-epigenetic coupling orchestrated by the ATF4-MAT2A axis for angiogenesis. The ATF4-MAT2A axis links lipid overload milieu to altered epigenetic status of relevant angiogenic signaling in endothelial cells, suggesting a potential therapeutic target for angiogenesis impaired by lipid overload.
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http://dx.doi.org/10.1096/fj.202100233RDOI Listing
June 2021

Perceived urban green and residents' health in Beijing.

SSM Popul Health 2021 Jun 8;14:100790. Epub 2021 Apr 8.

Key Laboratory of Region Sustainable Development Modeling, CAS, Beijing, 100101, China.

Green space serves urban residents in various functions including promoting health, but the roles of different types of green space are unclear. A survey titled "Healthy Neighborhood" was conducted in Beijing from May to July 2019 to examine and compare the associations between three types of perceived green space (park green, public-square green and utility green) and three aspects of residents' health (physical health, mental health and social health). Results from the multilevel modeling (MLM) analysis show that the perceived park green has a positive correlation with mental health, and all three types of perceived green space correlate with social health positively. No significant correlation of any type of green space is detected on participants' physical health, nor any relation of public-square green or utility green to their mental health. Overall the role of urban green space is stronger on social health than physical and mental health. The findings support the complementary roles of different types of green space, and suggest that expansion in utility greens could be as effective as investing in more costly park and public-square greens, especially in their benefit in promoting social health.
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http://dx.doi.org/10.1016/j.ssmph.2021.100790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080077PMC
June 2021

Serum-derived extracellular vesicles inhibit osteoclastogenesis in active-phase patients with SAPHO syndrome.

Ther Adv Musculoskelet Dis 2021 16;13:1759720X211006966. Epub 2021 Apr 16.

State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, No. 5 Dong Dan San Tiao, Beijing, 100005, China.

Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome.

Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism.

Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation.

Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.
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http://dx.doi.org/10.1177/1759720X211006966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053764PMC
April 2021