Publications by authors named "Xiaohong Li"

950 Publications

Kawasaki Disease- Management Strategies Given Symptoms Overlap to COVID-19: A Review.

JNMA J Nepal Med Assoc 2021 Apr 30;59(236):417-424. Epub 2021 Apr 30.

Children's Hospital of Shaanxi Provincial People's Hospital, 3rd Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an Shanxi, 710001, China.

Kawasaki disease is an acute, self-limiting vasculitis in children. Early treatment is necessary to prevent cardiovascular complications. The acute phase of Kawasaki disease may present with hemodynamic instability. An association between viral respiratory infections and Kawasaki disease has been reported. Studies have shown that Kawasaki and Kawasaki-like disease may be associated with and have symptoms overlapping COVID-19. Children with COVID-19 may present as Kawasaki-like disease with pediatric inflammatory multisystem syndrome, or macrophage activation syndrome. Clinicians need to be aware of the early diagnosis and management of Kawasaki disease to prevent the development of coronary artery aneurysms. The symptoms overlap of multisystem inflammatory disease seen in COVID-19 adds to the difficulties in timely diagnosis and treatment. Children with Kawasaki disease require regular follow-up plans for coronary artery aneurysms. This adds to the difficulties during the changed environment of COVID-19 for control and prevention. Missed diagnosis and early treatment of Kawasaki disease with immunoglobulin and aspirin results in the development of coronary artery aneurysm in up to 25% of cases, with grave consequences. Here, we briefly review the management of typical and atypical Kawasaki disease which has symptoms overlapping with the multisystem inflammatory disease as seen in COVID-19.
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http://dx.doi.org/10.31729/jnma.5698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369595PMC
April 2021

Abnormal Neural Activity in Different Frequency Bands in Parkinson's Disease With Mild Cognitive Impairment.

Front Aging Neurosci 2021 20;13:709998. Epub 2021 Aug 20.

Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

: Abnormal spontaneous neural activity is often found in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps. : Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups. : In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III). : Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI.
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http://dx.doi.org/10.3389/fnagi.2021.709998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417797PMC
August 2021

Proteomic Analysis of Hypoxia-Induced Senescence of Human Bone Marrow Mesenchymal Stem Cells.

Stem Cells Int 2021 27;2021:5555590. Epub 2021 Aug 27.

Research Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Methods: Hypoxia in hBMSCs was induced for 0, 4, and 12 hours, and cellular senescence was evaluated by senescence-associated -galactosidase (SA--gal) staining. Tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of hypoxia in hBMSCs. Parallel reaction monitoring (PRM) analysis was used to validate the candidate proteins. Verifications of signaling pathways were evaluated by western blotting. Cell apoptosis was evaluated using Annexin V/7-AAD staining by flow cytometry. The production of reactive oxygen species (ROS) was detected by the fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA).

Results: Cell senescence detected by SA--gal activity was higher in the 12-hour hypoxia-induced group. TMT analysis of 12-hour hypoxia-induced cells identified over 6000 proteins, including 686 differentially expressed proteins. Based on biological pathway analysis, we found that the senescence-associated proteins were predominantly enriched in the cancer pathways, PI3K-Akt pathway, and cellular senescence signaling pathways. CDK1, CDK2, and CCND1 were important nodes in PPI analyses. Moreover, the CCND1, UQCRH, and COX7C expressions were verified by PRM. Hypoxia induction for 12 hours in hBMSCs reduced CCND1 expression but promoted ROS production and cell apoptosis. Such effects were markedly reduced by the PI3K agonist, 740 Y-P, and attenuated by LY294002.

Conclusions: Hypoxia of hBMSCs inhibited CCND1 expression but promoted ROS production and cell apoptosis through activating the PI3K-dependent signaling pathway. These findings provided a detailed characterization of the proteomic profiles related to hypoxia-induced senescence of hBMSCs and facilitated our understanding of the molecular mechanisms leading to stem cell senescence.
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http://dx.doi.org/10.1155/2021/5555590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416403PMC
August 2021

Surface decoration of black phosphorus nanosheets to generate oxygen and release O for photodynamic killing of bacteria.

Nanoscale 2021 Aug 2;13(31):13506-13518. Epub 2021 Aug 2.

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P.R. China.

Photodynamic therapy (PDT) has evolved as an essential method for infection control, but is confronted with challenges in terms of low oxygen supply, possible toxicity during light irradiation, and nonpersistent action. Herein, to address these limitations, black phosphorus (BP) is used as a photosensitizer and decorated with Pt nanoparticles and aminobenzyl-2-pyridone (APy) moieties to obtain [email protected] The stability of BP is improved through the capture and occupation of lone-pair electrons after reductive deposition of Pt nanoparticles and covalent conjugation of APy. Pt nanoparticles on [email protected] catalyze the decomposition of endogenous HO to produce oxygen for consecutive cycles with a stable production capacity. The light exposure to [email protected] generates significantly higher O levels than those of BP/light, and the generated O is partially captured by APy moieties. The captured O during 20 min of illumination shows a constant release for 24 h in the dark. The cycled storage and release feature eliminates the toxicity of O at high levels during illumination and leads to efficient destruction of S. aureus and P. aeruginosa. Compared to the healing rates after treatment with BP/light (57.6%), [email protected]/light (64.8%), [email protected]/light (77.8%), and [email protected] (48.5%), the skin wounds with infected S. aureus are fully healed after [email protected]/light treatment. Blood vessels and hair follicles are regenerated to resemble those of normal skin. Thus, this study expands the PDT strategy through integration with oxygen generation, O storage, and persistent release to promote bactericidal efficacy and eliminate side effects.
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http://dx.doi.org/10.1039/d1nr02605dDOI Listing
August 2021

Protocol of a prospective and multicentre China Teratology Birth Cohort (CTBC): association of maternal drug exposure during pregnancy with adverse pregnancy outcomes.

BMC Pregnancy Childbirth 2021 Sep 1;21(1):593. Epub 2021 Sep 1.

Key Laboratory of Birth Defects And Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.

Background: As reported, 27-93 % of pregnant women take at least one drug during pregnancy. However, drug exposure during pregnancy still lacks sufficient foetal safety evidence of human origin. It is urgent to fill the knowledge gap about medication safety during pregnancy for optimization of maternal disease treatment and pregnancy drug consultation.

Methods And Analysis: The China Teratology Birth Cohort (CTBC) was established in 2019 and is a hospital-based open-ended prospective cohort study with the aim of assessing drug safety during pregnancy. Pregnant women who set up the pregnancy health records in the first trimester or who seek drug consultation regardless of gestational age in the member hospitals are recruited. Enrolled pregnant women need to be investigated four times, namely, 6-14 and 24-28 weeks of gestational age, before discharge after hospital delivery, and 28-42 days after birth. Maternal medication exposure during pregnancy is the focus of the CTBC. For drugs, information on the type, name, and route of medication; start and end time of medication; single dose; frequency of medication; dosage form; manufacturer; and reason for medication is collected. The adverse pregnancy outcomes collected in the study include birth defects, stillbirth, spontaneous abortion, preterm birth, post-term birth, low birth weight, macrosomia, small for gestational age, large for gestational age and low Apgar score. CTBC uses an electronic questionnaire for data collection and a cloud system for data management. Biological samples are collected if informed consents are obtained. Multi-level logistic regression, mixed-effect negative binomial distribution regression and spline function regression are used to explore the effect of drugs on the occurrence of birth defects.

Discussion: The findings of the study will assist in further understanding the risk of birth defects and other adverse pregnancy outcomes associated with maternal drug exposure and developing the optimal treatment plans and drug counselling for pregnant women.

Trial Registration: This study was approved by the Research Ethics Committee of the West China Second Hospital of Sichuan University and registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx , registration number ChiCTR1900022569 ).
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http://dx.doi.org/10.1186/s12884-021-04073-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411516PMC
September 2021

Preterm births in China between 2012 and 2018: an observational study of more than 9 million women.

Lancet Glob Health 2021 09;9(9):e1226-e1241

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; Med-X Center for Informatics, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China; Key Laboratory of Chronobiology (Sichuan University), National Health Commission of China, Chengdu, China.

Background: Preterm birth rates have increased significantly worldwide over the past decade. Few epidemiological studies on the incidence of preterm birth and temporal trends are available in China. This study used national monitoring data from China's National Maternal Near Miss Surveillance System (NMNMSS) to estimate the rate of preterm birth and trends between 2012 and 2018 in China and to assess risk factors associated with preterm birth.

Methods: In this observational study, data were sourced from the NMNMSS between Jan 1, 2012, and Dec 31, 2018. Pregnancies with at least one livebirth, with the baby born at 28 weeks of gestation or more or 1000 g or more birthweight were included. We estimated the rates of overall preterm, very preterm (born between 28 and 31 weeks' gestation), moderate preterm (born between 32 and 33 weeks' gestation), and late preterm (born between 34 and 36 weeks' gestation) births in singleton and multiple pregnancies and assessed their trends over time. We used logistic regression analysis to examine the associations between preterm birth and sociodemographic characteristics and obstetric complications, considering the sampling strategy and clustering of births within hospitals. Interrupted time series analysis was used to assess the changes in preterm birth rates during the period of the universal two child policy intervention.

Findings: From Jan 1, 2012, to Dec 31, 2018, 9 645 646 women gave birth to at least one live baby, of whom 665 244 (6·1%) were born preterm. In all pregnancies, the overall preterm birth rate increased from 5·9% in 2012 to 6·4% in 2018 (8·8% increase; annual rate of increase [ARI] 1·3 [95% CI 0·6 to 2·1]). Late preterm births (8·8%; ARI 1·5% [0·9 to 2·2]) and very preterm births (13·3%; ARI 1·8% [0·5 to 3·0]) significantly increased from 2012 to 2018, whereas moderate preterm births did not (3·8%; ARI 0·3% [95% CI -0·9 to 1·5]). In singleton pregnancies, the overall preterm birth rate showed a small but significant 6·4% increase (ARI 1·0% [0·4 to 1·7]) over the 7 year period. In multiple pregnancies, the overall preterm birth rate significantly increased from 46·8% in 2012 to 52·7% in 2018 (12·4% increase; ARI 1·9% [1·2 to 2·6]). Compared with women who gave birth in 2012, those who gave birth in 2018 were more likely to be older (aged ≥35 years; 7·4% in 2012 vs 15·9% in 2018), have multiples (1·6% vs 1·9%), have seven or more antenatal visits (50·2% vs 70·7%), and have antepartum complications and medical disease (17·9% vs 35·1%), but they were less likely to deliver via caesarean section (47·5% vs 45·0%). Compared with the baseline period (January, 2012 to June, 2016), a higher increase in preterm birth was observed after the universal two child policy came into effect in July, 2016 (β=0·034; p=0·03).

Interpretation: An increase in preterm births was noted for both singleton and multiple pregnancies between 2012 and 2018 in China. China's strategic investment in maternal and neonatal health has been crucial for the prevention of preterm birth. Due to rapid changes in sociodemographic and obstetric factors related to preterm birth-particularly within the context of the universal two child policy-such as advanced maternal age at delivery, maternal complications, and multiple pregnancies, greater efforts to reduce the burden of preterm birth are urgently needed.

Funding: National Key R&D Program of China, National Health Commission of the People's Republic of China, China Medical Board, WHO, and UNICEF.
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http://dx.doi.org/10.1016/S2214-109X(21)00298-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386289PMC
September 2021

Efficacy and safety of the Chinese herbal formula Hewei Jiangni recipe for NERD with cold-heat complex syndrome: study protocol for a double-blinded randomized controlled trial.

Trials 2021 Aug 18;22(1):545. Epub 2021 Aug 18.

Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6 fangxingyuan Fengtai District, Beijing, 100078, China.

Background: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites.

Methods: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively.

Discussion: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.
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http://dx.doi.org/10.1186/s13063-021-05471-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371854PMC
August 2021

Dietary fats high in linoleic acids impair anti-tumor T cell responses by inducing E-FABP-mediated mitochondrial dysfunction.

Cancer Res 2021 Aug 16. Epub 2021 Aug 16.

Microbiology and Immunology, University of Louisville

The most recent American Dietary Guidelines (2020-2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired anti-tumor T cell responses by promoting naïve T cell apoptosis and inhibiting TNFα production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial ROS production and lipid peroxidation. Importantly, naïve T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP-mediated T cell dysfunction.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0757DOI Listing
August 2021

Ultrasonic signal enhancement for coarse grain materials by machine learning analysis.

Ultrasonics 2021 Dec 11;117:106550. Epub 2021 Aug 11.

Key Laboratory of Hydraulic Machinery Transients, Ministry of Education, School of Power and Mechanical Engineering, Wuhan University, 430072 Wuhan, Hubei, China.

This paper aims at dealing with the dilemma of examining the existence of a defect in ultrasonic detection of coarse grain materials. In such cases, defect echoes can be drowned in a strong noise background resulting from intricate coarse grain scattering, that is, grain noise. To this end, we develop an innovative signal reconstruction methodology from polluted measurements which combines basic statistical analysis with a series of machine learning algorithms. The proposed methodology analyzes abundant information from numerous raw signals to distinguish the desired signal from grain noise, avoiding the limitation of information provided only by a single signal. The technique is achieved by collecting similar signals together through a clustering algorithm and subsequently inputting these similar signals to a denoising autoencoder to suppress the grain noise. It is successfully employed to ultrasonic signals obtained from an as-cast stainless steel specimen with coarse equiaxed grains, a stainless steel specimen with relatively homogeneous dendrite fabricated by additive manufacturing and a stainless steel weld with heterogeneous columnar grains having variation of grain sizes in various locations. The influence of material microstructure and probe frequency on denoising performance is investigated in detail. Based on this, the proposed methodology is applied to defect detection. Desired A-scan results and B-scan imaging are achieved by the proposed method, where defects are well revealed. The experimental results demonstrate the developed methodology has stable excellent performance and superior denoising capabilities for defect detection with respect to conventional techniques, especially in the case where the noise is almost the same as the desired signal.
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http://dx.doi.org/10.1016/j.ultras.2021.106550DOI Listing
December 2021

Plasmonic Hot Hole Extraction from CuS Nanodisks Enables Significant Acceleration of Oxygen Evolution Reactions.

J Phys Chem Lett 2021 Aug 16;12(33):7988-7996. Epub 2021 Aug 16.

Guangdong Key Laboratory of Nano-Micro Material Research, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen 518055, China.

Localized surface plasmon resonance (LSPR) is well known for its unique ability to tune the reactivity of plasmonic materials via photoexcitation; however, it is still an open question as to whether plasmonic holes can be directly extracted to drive valuable chemical reactions. Herein we give an affirmative answer by reporting an illumination-enhanced oxygen evolution reaction (OER) using CuS nanodisks (NDs) alone as the electrocatalyst. Impressively, under 1221 nm laser or xenon lamp illumination, an unprecedented reduction of OER overpotential was observed on the CuS ND-coated electrodes. Transient absorption combined with Mott-Schottky measurements disclosed that near-infrared (NIR) irradiation generated abundant hot holes from LSPR damping in the CuS NDs accounting for the remarkable OER performance enhancement. This is the first report on the direct utilization of plasmonic hot holes in CuS nanomaterials for boosting OER performance, opening up a new route to designing NIR-active photocatalysts/electrocatalysts by exploiting the unique LSPR properties.
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http://dx.doi.org/10.1021/acs.jpclett.1c01950DOI Listing
August 2021

MicroRNAs Involved in the Therapeutic Functions of Noni ( L.) Fruit Juice in the Treatment of Acute Gouty Arthritis in Mice Induced with Monosodium Urate.

Foods 2021 Jul 15;10(7). Epub 2021 Jul 15.

College of Food Engineering, Jilin Engineering Normal University, Changchun 130052, China.

We investigated the functions of microRNAs in the therapeutic effects of noni ( L.) fruit juice on mouse models of acute gouty arthritis induced with monosodium urate (MSU). Compared with the model group (treated with MSU), mice in both the positive control group (treated with both MSU and colchicine) and noni fruit juice group (treated with MSU and noni fruit juice) showed a significantly decreased degree of paw swelling in 5 days, as well as the contents of two types of proinflammatory cytokines (i.e., NALP3 and TNF-α). Based on the next-generation sequencing technology, a total of 3896 microRNAs (234 known and 3662 novel) were identified in mice treated with noni fruit juice. A large amount of differentially expressed miRNAs were identified in the noni fruit juice group, suggesting the significant effects of noni fruit juice on the mice with acute gouty arthritis, while the different patterns of change in the numbers of both upregulated and downregulated miRNAs in both noni fruit juice and positive control groups indicated that the mice of acute gouty arthritis may be regulated by differential mechanisms between the treatments of noni fruit juice and colchicine. The target genes of microRNAs involved in the pathogenesis and pathology of acute gouty arthritis in mice were identified and further annotated by both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our results revealed the therapeutic effects of noni fruit juice on acute gouty arthritis in mice with a group of microRNAs involved in the pharmacological mechanisms of noni fruit juice, providing scientific evidence to support both the agricultural cultivation and pharmacological significance of noni plants.
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http://dx.doi.org/10.3390/foods10071638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308103PMC
July 2021

Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice.

Genes (Basel) 2021 Jul 10;12(7). Epub 2021 Jul 10.

Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY 40202, USA.

Exposure to fine particulate matter (PM) air pollution is associated with quantitative deficits of circulating endothelial progenitor cells (EPCs) in humans. Related exposures of mice to concentrated ambient PM (CAP) likewise reduces levels of circulating EPCs and induces defects in their proliferation and angiogenic potential as well. These changes in EPC number or function are predictive of larger cardiovascular dysfunction. To identify global, PM-dependent mRNA and miRNA expression changes that may contribute to these defects, we performed a transcriptomic analysis of cells isolated from exposed mice. Compared with control samples, we identified 122 upregulated genes and 44 downregulated genes in EPCs derived from CAP-exposed animals. Functions most impacted by these gene expression changes included regulation of cell movement, cell and tissue development, and cellular assembly and organization. With respect to miRNA changes, we found that 55 were upregulated while 53 were downregulated in EPCs from CAP-exposed mice. The top functions impacted by these miRNA changes included cell movement, cell death and survival, cellular development, and cell growth and proliferation. A subset of these mRNA and miRNA changes were confirmed by qRT-PCR, including some reciprocal relationships. These results suggest that PM-induced changes in gene expression may contribute to EPC dysfunction and that such changes may contribute to the adverse cardiovascular outcomes of air pollution exposure.
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http://dx.doi.org/10.3390/genes12071058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307414PMC
July 2021

Endometrial thickness in the prediction of neonatal adverse outcomes in frozen cycles for singleton pregnancies.

Reprod Biomed Online 2021 Apr 24. Epub 2021 Apr 24.

Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia.

Research Question: Does endometrial thickness (EMT) predict adverse neonatal outcomes in singleton pregnancies after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) frozen embryo transfer (FET)?

Design: This retrospective study involved 13,383 women undergoing IVF/ICSI FET cycles between January 2010 and December 2018 in Women's Hospital of Zhejiang University. The primary outcome was preterm delivery (PTD). The secondary outcomes were small for gestational age (SGA), large for gestational age (LGA) and low birthweight (LBW).

Results: A total of 13,383 FET cycles resulting in 5220 singleton live births and 8163 failed cycles were included. Multiple spline regression visualization showed an increasing risk of PTD and LBW for a thin EMT. By comparing multiple cut-off points using area under the curve, a cut-off point of 8 mm was identified, which was used to categorize EMT. A reference point of EMT greater than 8 mm was used; after adjusting for covariates, individuals with EMT less than 8 mm had an adjusted odds ratio of 1.75 (95% CI 1.30 to 2.34) for PTD, 1.57 (95% CI 1.09 to 2.26) for LBW, 0.97 (95% CI 0.63 to 1.50) for SGA and 1.04 (95% CI 0.79 to 1.37) for LGA. Additional analyses showed similar increasing risk with a thin endometrium for both PTD with and without caesarean section, and PTD with low and normal birthweight percentiles.

Conclusion: A clinical cut-off point of 8 mm has been identified, below which risk of PTD and LBW increases in women undergoing IVF/ICSI.
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http://dx.doi.org/10.1016/j.rbmo.2021.04.014DOI Listing
April 2021

Heterophyllin B, a cyclopeptide from Pseudostellaria heterophylla, enhances cognitive function via neurite outgrowth and synaptic plasticity.

Phytother Res 2021 Jul 30. Epub 2021 Jul 30.

College of Food Science and Technology, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Institute of Nutrition and Marine Drugs, Guangdong Ocean University, Zhanjiang, China.

Neurite outgrowth-induced construction of neural circuits and networks is responsible for memory generalization, consolidation, and retrieval. In this study, we found that the traditional Chinese medicine Pseudostellaria heterophylla promoted neurite regrowth and enhanced cognitive function in normal mice. Further, we orally administered Pseudostellaria heterophylla water extracts (PHE) to ICR mice, and detected heterophyllin B (HET-B), an important cyclopeptide, in the plasma and cerebral cortex. We demonstrated that neurites were significantly elongated after coculturing with HET-B for 4 days. Next, the intraperitoneal injection of HET-B on seven consecutive days in 3-month-old ICR mice significantly enhanced the object recognition memory and object location memory than that in control. Immunohistochemical analysis indicated significantly increased β3-tubulin-positive neurite density, synaptophysin, and postsynaptic density 95 in the perirhinal cortex and hippocampus after administering HET-B. Furthermore, the concentration of neurotransmitters was measured using HPLC analysis; HET-B significantly increased five-levels of HT in the hippocampus, and decreased metabolites of dopamine, dihydroxyphenylacetic acid, and homovanillic acid, in the prefrontal cortex and hippocampus. Taken together, HET-B induces neurite elongation and neurotransmitter regulation and possibly enhances cognitive memory.
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http://dx.doi.org/10.1002/ptr.7212DOI Listing
July 2021

Polymorphism rs11200638 enhanced HtrA1 responsiveness and expression are associated with age-related macular degeneration.

Eye (Lond) 2021 Jul 29. Epub 2021 Jul 29.

Xiamen Eye Center, Xiamen University, Xiamen, China.

Objectives: To investigate the role of polymorphism rs11200638 of high-temperature requirement factor A-1 (HtrA1) gene in the pathogenesis of age-related macular degeneration (AMD).

Methods: Cultured adult retinal pigment epithelial cells (ARPE-19) expressing HtrA1 gene were treated with HO or lipopolysaccharides (LPS) and analysed using western blot and quantitative polymerase chain reaction to illustrate the effects of oxidative and inflammatory stress on HtrA1 gene expression. Luciferase reporter plasmid driven by HtrA1 promoter with either normal allele G or risk allele A at SNP rs11200638 was transfected to ARPE-19 cells to investigate the effect of the G/A variation on HtrA1 promoter activity. The effects of HtrA1 overexpression on ARPE-19 cells were analysed with respect to percentage of cell proliferation inhibition and cell apoptosis.

Results: HtrA1 expression was significantly increased with LPS or HO stimulations (p < 0.05). In ARPE-19 cells, HtrA1 promoters (-1 to -2175 bp from translation starting point) with risk allele A or normal G at rs11200638 did not show statistically significant differences in their luciferase reporter expression (p = 0.054425173), however, both promoters showed a persistent trend of higher luciferase expressions after 100 ng/ml LPS treatment. The luciferase expression level was significantly greater in the promoter with risk A when compared to that with normal G. Overexpression of HtrA1 resulted in apoptosis of ARPE-19 cells with 53.8 ± 1.6% of proliferation inhibition (p < 0.01).

Conclusions: Risk haplotype A at rs11200638 significantly increased the responsiveness of HtrA1 promoter to inflammation and subsequently enhanced HtrA1 expression. HtrA1 overexpression induced ARPE-19 apoptosis and growth inhibition, relevant to pathogenesis of AMD.
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http://dx.doi.org/10.1038/s41433-021-01706-8DOI Listing
July 2021

Directional Magnetization Reversal Enables Ultrahigh Energy Density in Gradient Nanostructures.

Adv Mater 2021 Sep 26;33(36):e2102800. Epub 2021 Jul 26.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao, 066004, China.

High-performance ferromagnetic materials are essential for energy conversion and electronic devices. However, the random and nonuniform magnetization reversal in ferromagnetics limits their performance that can be achieved. Here, through both micromagnetism simulations and experiments, a directional magnetization reversal that initiates first from large grains toward smaller ones is discovered by engineering Nd Fe B/α-Fe gradient nanostructures. Such directional magnetization reversal enables a rare combination of high magnetization and large coercivity, thus leading to a record-high energy density (26 MG Oe) for isotropic permanent magnetic materials, which is ≈50% higher than that of its gradient-free counterpart. The unusual magnetization reversal originates from an ordered arrangement of grain sizes in the gradient material, where the large grains have a lower reversal field than that of the smaller ones. These findings open up new opportunities for developing high-performance magnetic materials.
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http://dx.doi.org/10.1002/adma.202102800DOI Listing
September 2021

A comparison of the effects of two orthodontic techniques in the orthodontic treatment of sagittal skeletal patterns.

Am J Transl Res 2021 15;13(6):6221-6228. Epub 2021 Jun 15.

Department of Stomatology, Haikou Third People's Hospital Haikou 570105, Hainan, China.

Objective: To compare the differences in the amount of dental root resorption (DRR) measured using different orthodontic techniques in the orthodontic treatment of patients with different sagittal skeletal patterns.

Methods: Ninety-three patients undergoing orthodontic treatment were randomly divided into group A (n=46) and group B (n=47). Group A was treated with bracketless invisible orthodontics and group B was treated using the self-ligating fixed orthodontic technique. Cone beam computed tomography (CBCT) was used to measure the amount of DRR in the patients with different sagittal skeletal patterns receiving the orthodontic treatment.

Results: After the treatment, the amounts of DRR in the maxillary and mandibular canines in both groups were lower than they were in the other 4 tooth positions ( < 0.05). The amount of DRR in the maxillary and mandibular canines in the patients with skeletal class I in both groups was lower than it was at the other four tooth positions ( < 0.05). The amount of DRR in the maxillary central incisors and maxillary canines in the patients with skeletal class II in group A was higher than it was in group B, but the amount of DRR in the mandibular canines in group A was lower than it was in group B ( < 0.05). The amounts of DRR at the six tooth positions in the patients with skeletal class III in group A were higher than the amounts in group B ( < 0.05).

Conclusion: DRR occurs in patients with different sagittal skeletal patterns undergoing the two orthodontic techniques in the orthodontic treatment, but there are differences in the amount of DRR among the patients with different sagittal skeletal patterns receiving the orthodontic treatment. Clinically, the orthodontic method should be selected based on the type of patient.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290744PMC
June 2021

Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method.

BMC Infect Dis 2021 Jul 23;21(1):702. Epub 2021 Jul 23.

State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China.

Background: Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its' metabolic activity regarding different lesion characteristics.

Methods: A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using F-fluodeoxyglucose (F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of F-FDG standard uptake value (SUV, n = 75) was calculated, and range of F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges.

Results: Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values.

Conclusions: PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.
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http://dx.doi.org/10.1186/s12879-021-06366-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299608PMC
July 2021

Engineering a probiotic strain of Escherichia coli to induce the regression of colorectal cancer through production of 5-aminolevulinic acid.

Microb Biotechnol 2021 Sep 16;14(5):2130-2139. Epub 2021 Jul 16.

State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao, Shandong, 266237, China.

Bacterial vectors can be engineered to generate microscopic living therapeutics to produce and deliver anticancer agents. Escherichia coli Nissle 1917 (Nissle 1917) is a promising candidate with probiotic properties. Here, we used Nissle 1917 to develop a metabolic strategy to produce 5-aminolevulinic acid (5-ALA) from glucose as 5-ALA plays an important role in the photodynamic therapy of cancers. The coexpression of hemA and hemL using a low copy-number plasmid led to remarkable accumulation of 5-ALA. The downstream pathway of 5-ALA biosynthesis was inhibited by levulinic acid (LA). Small-scale cultures of engineered Nissle 1917 produced 300 mg l of 5-ALA. Recombinant Nissle 1917 was applied to deliver 5-ALA to colorectal cancer cells, in which it induced the accumulation of antineoplastic protoporphyrin X (PpIX) and specific cytotoxicity towards colorectal cancer cells irradiated with a 630 nm laser. Moreover, this novel combination therapy proved effective in a mouse xenograft model and was not cytotoxic to normal tissues. These findings suggest that Nissle 1917 will serve as a potential carrier to effectively deliver 5-ALA for cancer therapy.
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http://dx.doi.org/10.1111/1751-7915.13894DOI Listing
September 2021

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK.

PLoS One 2021 15;16(7):e0252048. Epub 2021 Jul 15.

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Harvard University, Boston, Massachusetts, United States of America.

Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas. These efforts identified brigatinib (ALUNBRIG®), an FDA-approved inhibitor of multiple tyrosine kinases including ALK, to be a potent inhibitor of tumor growth in established NF2 deficient xenograft meningiomas and a genetically engineered murine model of spontaneous NF2 schwannomas. Surprisingly, neither meningioma nor schwannoma cells express ALK. Instead, we demonstrate that brigatinib inhibited multiple tyrosine kinases, including EphA2, Fer and focal adhesion kinase 1 (FAK1). These data demonstrate the power of the de novo unbiased approach for drug discovery and represents a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252048PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282008PMC
July 2021

Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.
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http://dx.doi.org/10.1073/pnas.2106786118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285956PMC
July 2021

Endogenous ω-3 fatty acids in Fat-1 mice attenuated depression-like behaviors, spatial memory impairment and relevant changes induced by olfactory bulbectomy.

Prostaglandins Leukot Essent Fatty Acids 2021 Aug 24;171:102313. Epub 2021 Jun 24.

Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; Shenzhen Institute of Guangdong Ocean University, Shenzhen, China. Electronic address:

Objectives: Olfactory bulbectomy (OB) induced behaviors, hypercortisolism, inflammation and neurotrophin dysfunctions are similar to those observed in depressed patients. Omega (n)-3 polyunsaturated fatty acids (PUFAs) can effectively treat depression via anti-inflammatory and neuroprotective effects. However, n-3 PUFA purities, caloric contents, and ratios in different diets often cause contradictive results. This study used Fat-1 mice, which can convert n-6 to n-3 PUFAs in the brain, to study the effect of n-3 PUFAs on OB-induced behaviors and related changes.

Methods: Fat-1 and wild-type littermates were fed safflower oil for 3 months. Behaviors were tested on day 21 after surgery. Monoamine neurotransmitters were measured by HPLC. Macrophage activity was measured by MTT assay. Astrocyte phenotypes A1 S100β, A2 BDNF and cholesterol level were measured by ELISA and total cholesterol assay kits respectively. PUFA profile and membrane fluidity were detected by GC and DPH fluorescence probe respectively.

Results: OB significantly induced animal hyperactivity and spatial memory impairment, while decreased sucrose consumption and social contact with decreased 5-HT turnover, increased the macrophage activity and S100β/BDNF ratio. Meanwhile, n-3/n-6 PUFAs ratio and total cholesterol level were reduced in OB mice. Whereas, OB-induced behavioral changes were attenuated, which were associated with increasing 5-HT turnover, decrease macrophage activity, restored S100β/BDNF and n-3/n-6 PUFAs ratios, and total cholesterol concentrations in Fat-1 mice.

Conclusion: The present study for the first time demonstrated that endogenous n-3 PUFAs attenuated OB-induced depression-like behaviors and spatial memory impairment through modulating serotonergic and immune function, balancing the astrocyte A1/A2 phenotypes, and normalizing PUFAs profile and membrane function.
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http://dx.doi.org/10.1016/j.plefa.2021.102313DOI Listing
August 2021

Magnetic resonance imaging radiomics predicts preoperative axillary lymph node metastasis to support surgical decisions and is associated with tumor microenvironment in invasive breast cancer: A machine learning, multicenter study.

EBioMedicine 2021 Jul 4;69:103460. Epub 2021 Jul 4.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: in current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer has a low efficiency and is based on an invasive procedure that causes operative-associated complications in many patients. Therefore, we aimed to use machine learning techniques to develop an efficient preoperative magnetic resonance imaging (MRI) radiomics evaluation approach of ALN status and explore the association between radiomics and the tumor microenvironment in patients with early-stage invasive breast cancer.

Methods: in this retrospective multicenter study, three independent cohorts of patients with breast cancer (n = 1,088) were used to develop and validate signatures predictive of ALN status. After applying the machine learning random forest algorithm to select the key preoperative MRI radiomic features, we used ALN and tumor radiomic features to develop the ALN-tumor radiomic signature for ALN status prediction by the support vector machine algorithm in 803 patients with breast cancer from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (training cohort). By combining ALN and tumor radiomic features with corresponding clinicopathologic information, the multiomic signature was constructed in the training cohort. Next, the external validation cohort (n = 179) of patients from Shunde Hospital of Southern Medical University and Tungwah Hospital of Sun Yat-Sen University, and the prospective-retrospective validation cohort (n = 106) of patients treated with neoadjuvant chemotherapy in prospective phase 3 trials [NCT01503905], were included to evaluate the predictive value of the two signatures, and their predictive performance was assessed by the area under operating characteristic curve (AUC). This study was registered with ClinicalTrials.gov, number NCT04003558.

Findings: the ALN-tumor radiomic signature for ALN status prediction comprising ALN and tumor radiomic features showed a high prediction quality with AUC of 0·88 in the training cohort, 0·87 in the external validation cohort, and 0·87 in the prospective-retrospective validation cohort. The multiomic signature incorporating tumor and lymph node MRI radiomics, clinical and pathologic characteristics, and molecular subtypes achieved better performance for ALN status prediction with AUCs of 0·90, 0·91, and 0·93 in the training cohort, the external validation cohort, and the prospective-retrospective validation cohort, respectively. Among patients who underwent neoadjuvant chemotherapy in the prospective-retrospective validation cohort, there were significant differences in the key radiomic features before and after neoadjuvant chemotherapy, especially in the gray-level dependence matrix features. Furthermore, there was an association between MRI radiomics and tumor microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites. Interpretation this study presented a multiomic signature that could be preoperatively and conveniently used for identifying patients with ALN metastasis in early-stage invasive breast cancer. The multiomic signature exhibited powerful predictive ability and showed the prospect of extended application to tailor surgical management. Besides, significant changes in key radiomic features after neoadjuvant chemotherapy may be explained by changes in the tumor microenvironment, and the association between MRI radiomic features and tumor microenvironment features may reveal the potential biological underpinning of MRI radiomics.

Funding: No funding.
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http://dx.doi.org/10.1016/j.ebiom.2021.103460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261009PMC
July 2021

Clinicopathological characteristics of patients with paraproteinemia and renal damage.

Eur J Med Res 2021 Jul 3;26(1):68. Epub 2021 Jul 3.

Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China.

Background: This study aimed to analyze the clinicopathological characteristics of patients with paraproteinemia and renal damage.

Methods: Ninety-six patients from 2014 to 2018 with paraproteinemia and renal damage were enrolled and the clinical data, renal pathology, treatment and prognosis data were collected.

Results: A total of 96 patients (54 male and 42 female), accounting for 2.7% of all renal biopsies, were enrolled in this study. Among them, 42 were monoclonal gammopathy of renal significance (MGRS), 21 were renal monotypic immunoglobulin alone (renal monoIg), and 19 were monoclonal gammopathy of undetermined significance (MGUS). Individuals with multiple myeloma (MM) accounted for the fewest number of patients (n  =  14). In the MGRS group, the main diseases were amyloidosis (n  =  25) and cryoglobulinemic glomerulonephritis (n  =  7), while in the MM group, the main diseases were cast nephropathy (n  =  9) and light chain deposit disease (n  =  3). In the MGUS group, it was mainly IgA nephropathy (IgAN, n  =  10) and idiopathic membranous nephropathy (n  =  5); while in the renal monoIg group, most of the cases were IgAN (n  =  19). Chemotherapy was mainly administered to patients in the MM group, while immunosuppression therapy was mostly administered to patients in the renal monoIg group. Most patients with renal monoIg exhibited a major response, followed by the patients with MGUS and MGRS, while most of the patients with MM had a partial response but none had a major response. Approximately more than half (57.1%) of the patients with MM progressed to end-stage renal disease (ESRD), followed by MGRS (33.3%); however, the mortality rate was low in both the MGRS and MM groups. The survival analysis reviewed that serum creatinine, hemoglobin levels, and the serum κ/λ ratio were independent risk factors for ESRD in patients with MGRS.

Conclusions: The clinicopathological changes in patients with MGRS were between those in patients with MM and MGUS. The treatment for MGRS and MM was more intensive, and the overall mortality rate was low. Both MGUS and renal monoIg alone exhibited slighter clinicopathological features than MGRS and MM, and the treatment was focused mostly on primary renal diseases.
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http://dx.doi.org/10.1186/s40001-021-00538-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255003PMC
July 2021

Iron deposition-induced ferroptosis in alveolar type II cells promotes the development of pulmonary fibrosis.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 24;1867(12):166204. Epub 2021 Jun 24.

Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. Electronic address:

Ferroptosis is a newly discovered type of regulated cell death, characterized by the iron-dependent accumulation of lipid reactive oxygen species, which has been implicated in numerous human diseases. However, its role in pulmonary fibrosis, a fatal lung disease with unknown etiology, is largely unknown. Here, we investigated the role of ferroptosis in pulmonary fibrosis. We found a large amount of iron deposition in the lung tissue of patients with pulmonary fibrosis. We observed ferroptosis in alveolar type II (ATII) cells, fibrotic lung tissues of BLM-induced pulmonary fibrosis mice. BLM-induced increase in iron level was accompanied by pathological changes, collagen deposition, and ferroptosis in ATII cells, indicating iron deposition-induced ferroptosis, which promoted the development of pulmonary fibrosis. Moreover, deferoxamine (DFO) completely prevented the pro-fibrosis effects of BLM by reducing iron deposition and ferroptosis in ATII cells. Genes associated with intracellular iron metabolism and homeostasis, such as transferrin receptor 1, divalent metal transporter 1, and ferroportin-1, and showed abnormal expression levels in animal tissues and lung epithelial MLE-12 cells, which responded to BLM stimulation. Overall, we demonstrated that BLM-induced iron deposition in MLE-12 cells is prone to both mitochondrial dysfunction and ferroptosis and that DFO reverses this phenotype. In the future, understanding the role of ferroptosis may shed new light on the etiology of pulmonary fibrosis. Ferroptosis inhibitors or genetic engineering of ferroptosis-related genes might offer potential targets to treat pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.bbadis.2021.166204DOI Listing
June 2021

Bacterial navigation for tumor targeting and photothermally-triggered bacterial ghost transformation for spatiotemporal drug release.

Acta Biomater 2021 09 23;131:172-184. Epub 2021 Jun 23.

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China. Electronic address:

Cancer chemotherapy is confronted with challenges regarding the effective delivery of chemotherapeutics into tumor cells after systemic administration. Herein, we propose a strategy to load drugs into probiotic E. coli Nissle 1917 (EcN) for self-guided navigation to tumor tissues and subsequently release the drugs with in situ transformation into bacterial ghosts (BGs). Chemotherapeutic agent 5-fluorouracil (FU) and macrophage phenotype regulator zoledronic acid (ZOL) are loaded into EcN through electroporation, followed by decoration of Au nanorods on the ECN surface to construct [email protected] High loading levels of 5FU (8.8%) and ZOL (10.5%) are achieved as well as high retention rates of bacterial viability (87%) and motion velocity (88%). Under near infrared (NIR) illumination the photothermal effect of Au nanorods elevates the local temperature to induce the transformation of live EcN into BGs. The created transmembrane channels initiate the gradual drug release from BGs, thus representing the first attempt to control the drug release via a biological evolution. An intermittent NIR illumination causes stepwise increases in the BG formation and drug release, which could implement an external on-off control and spatiotemporal drug release. Self-guided motion of EcN promotes efficient extravasation across blood vessels and preferential accumulation of drugs in tumors. In addition to the chemotherapeutic effect of FU, the local release of ZOL from [email protected] enhances valid polarization of tumor-associated macrophages toward the M1 phenotype and an effective production of proinflammatory cytokines, leading to a synergistic efficacy on tumor growth inhibition. Thus, this study demonstrates a feasible strategy to integrate chemotherapy, immunotherapy, and photothermal effects in a concise manner for effective cancer treatment with few side effects. STATEMENT OF SIGNIFICANCE: Bacteria are capable to trace and colonize in hypoxic tumor tissues. Bacterial drug carriers indicate limitations in efficient drug loading and effective release modulation. Herein, we propose a strategy to load drugs into bacteria for self-guided delivery and subsequently release the drugs in tumors with in situ transformation into bacterial ghost (BGs). Drugs are loaded into live bacteria through electroporation and Au nanorods are decorated on the bacterial surface, wherein the photothermal effect, chemotherapy, and immunotherapy are integrated in a concise manner. NIR illmumination of Au nanorods elevates the local temparature, induces the BG tranformation, and activates the spatiotemporal drug release, representing the first attempt of release modulation via a biological evolution.
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http://dx.doi.org/10.1016/j.actbio.2021.06.030DOI Listing
September 2021

Metformin in Combination with Malvidin Prevents Progression of Non-Alcoholic Fatty Liver Disease via Improving Lipid and Glucose Metabolisms, and Inhibiting Inflammation in Type 2 Diabetes Rats.

Drug Des Devel Ther 2021 17;15:2565-2576. Epub 2021 Jun 17.

Department of Gastroenterology, Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of chronic liver disease and is closely linked to insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. However, no effective drug therapies have been approved to treat this disease. The present research aimed to evaluate the therapeutic effects of the combination of oral hypoglycemic drug metformin (MET) and a natural product malvidin (MAL) on hepatic damage in HFD/STZ-induced diabetic rats.

Methods: Sprague-Dawley rats were divided into five groups: normal control group (NC), diabetic control group (DC), DC+MET group, DC+MAL group, and DC+MET+MAL group and treated for eight weeks. Blood and liver tissue samples were collected for metabolic parameters, histological, and RT-qPCR analysis.

Results: Our findings indicated that hyperglycemia, insulin resistance, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) in diabetic rats were alleviated after oral treatment with MET and MAL, particularly their combination therapy. Besides, the expression of SREBP-1c, ACC, FAS, IL-6, IL-8, and NF-κB mRNA was down-regulated by MET+MAL, and the expression of PPARα, CPT1, and LPL was up-regulated by MET+MAL.

Conclusion: The evidence of this research indicated that the combination therapy may represent an efficient strategy against NAFLD in T2DM rats via improving lipid and glucose metabolisms, and inhibiting inflammation.
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http://dx.doi.org/10.2147/DDDT.S307257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218939PMC
June 2021

Investigation of the indoor 222Rn and 220Rn levels in the residential environment and estimation of the annual effective radiation dose for ordinary residents.

PLoS One 2021 24;16(6):e0253463. Epub 2021 Jun 24.

School of Public Health, Weifang Medical University, Weifang, Shandong Province, China.

To evaluate the health risk of radon and its progeny, a large amount of accurate monitoring data is needed according to the theory and practice of health risk assessment. However, the indoor radon levels in different regions in China and worldwide reveal temporal and spatial variations. In addition, the residents living in different areas follow distinct living modes. Therefore, it is recommended and accepted by many researchers to detect the radon level in local areas and subsequently conduct health risk assessments based on local detection data. In this study, 21 bedrooms of households in Weifang city were selected, and the indoor 222Rn and 220Rn levels were detected with RAD7 radon detector in winter, while the annual effective radiation dose was calculated for ordinary residents in Weifang city. Our investigation showed that the 24- and 12-hour average levels of 222Rn were 35.7±15.2 Bq/m3 and 36.2±15.8 Bq/m3, respectively. The 24- and 12-hour average levels of 220Rn were 30.4±12.3 Bq/m3 and 22.4±11.6 Bq/m3, respectively. There were significant differences in the average levels of 222Rn and 220Rn between floors. The estimated annual effective radiation dose received by ordinary residents in Weifang city was 1.7193 mSv, of which 0.9479 mSv originated from 222Rn and its progeny and 0.7714 mSv originated from 220Rn and its progeny, accounting for 55.1% and 44.9%, respectively, of the total dose. Our findings suggest that 220Rn should not be ignored by local residents in Weifang city, and more attention should be paid to 220Rn in future research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253463PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224870PMC
June 2021

Malignant transformation of ovarian teratoma responded well to immunotherapy after failed chemotherapy: a case report.

Ann Palliat Med 2021 Jul 21;10(7):8499-8505. Epub 2021 Jun 21.

Department of Oncology, Second Affiliated Hospital of Army Military Medical University, Chongqing, China.

Mature cystic teratomas (MCTs), also known as dermoid cysts, are the most common ovarian germ cell tumors and the most common ovarian neoplasms in patients younger than 20 years. MCTs mainly appear as pelvic masses that are made up of different types of well differentiated derivates of at least two germinative cell types. MCT of the ovary is always benign lesions with slow growth and good prognosis. Unfortunately, in about 1-2% of cases, it may undergo malignant transformation. At present, surgical treatment is the preferred option for the early stage of malignant transformation of teratomas, while with a high postoperative recurrence rate. For advanced or recurrent malignant ovarian teratomas, the effect of conventional chemotherapy or radiotherapy is poor, leading to high mortality. Thus, identifying novel treatment for malignant transformed MCTs is an urgently need in clinic. Recently, PD-1 antibody-based immunotherapy has achieved great success in treatment of lung cancer, melanoma, and other malignant tumors. However, its effect on the malignant transformation of ovarian teratomas has not yet been reported. Here we reported a patient who suffered malignant transformation of ovarian teratoma and responded well to camrelizumab, an anti-PD-1 inhibitor.
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http://dx.doi.org/10.21037/apm-20-2429DOI Listing
July 2021

Analysis of genotype-phenotype relationships in 90 Chinese probands with Waardenburg syndrome.

Hum Genet 2021 Jun 17. Epub 2021 Jun 17.

Key Lab of Hearing Impairment Science of Ministry of Education, Key Lab of Hearing Impairment Prevention and Treatment of Beijing, National Clinical Research Center for Otolaryngologic Diseases, College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, #28 Fuxing Road, Beijing, 100853, China.

Waardenburg syndrome (WS) is a phenotypically and genetically heterogeneous disorder characterised by hearing loss and pigmentary abnormalities. We clarified the clinical and genetic features in 90 Chinese WS probands. Disease-causing variants were detected in 55 probands, for a molecular diagnosis rate of 61%, including cases related to PAX3 (14.4%), MITF (24.4%), and SOX10 (22.2%). Altogether, 48 variants were identified, including 44 single-nucleotide variants and 4 copy number variants. By parental genotyping, de novo variants were observed in 60% of probands and 15.4% of the de novo variation was associated with mosaicism. Statistical analyses revealed that brown freckles on the skin were more frequently seen in probands with MITF variants; patchy depigmented skin, asymmetric hearing loss, and white forelocks occurred more often in cases with PAX3 variants; and congenital inner ear malformations were more common and cochlear hypoplasia III was exclusively observed in those with SOX10 variants. In addition, we found that ranges of W-index values overlapped between WS probands with different genetic variants, and the use of the W-index as a tool for assessing dystopia canthorum may be problematic in Chinese. Herein, we report the spectrum of a cohort of WS probands and elucidate the relationship between genotype and phenotype.
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http://dx.doi.org/10.1007/s00439-021-02301-3DOI Listing
June 2021
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