Publications by authors named "Yan Qi"

738 Publications

Hengshun Aromatic Vinegar Ameliorates Vascular Endothelial Injury Regulating PKCζ-Mediated Oxidative Stress and Apoptosis.

Front Nutr 2021 28;8:635232. Epub 2021 May 28.

College of Pharmacy, Dalian Medical University, Dalian, China.

Vascular endothelial injury (VEI) is an early event of atherosclerosis, and reversing endothelial dysfunction has become a new trend in the prevention and treatment of cardiovascular diseases. Hengshun aromatic vinegar (HSAV), a traditional vinegar, has been reported to have many pharmacological activities, but its effect against VEI and the molecular mechanism are still unknown. In this study, effects of HSAV on VEI were evaluated in HO-induced human umbilical vein endothelial cells (HUVECs) and methionine-induced VEI in rats. Results showed that HSAV significantly increased cell viability, inhibited apoptosis, and reduced the generation of reactive oxygen species (ROS) in HO-induced HUVECs. Meanwhile, HSAV decreased serum homocysteine (Hcy), endothelin 1 (ET-1), and oxidized low-density lipoprotein (ox-LDL) levels, increased nitric oxide (NO) and endothelin nitric oxide synthase (eNOS) levels, ameliorated pathological changes in rats with VEI induced by methionine. In parallel, HSAV relieved oxidative stress by decreasing malondialdehyde (MDA) level and increasing superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels in rats with VEI. Mechanism studies indicated that HSAV markedly downregulated the expression of protein kinase C zeta (PKCζ), and consequently regulated sirtuin 1 (Sirt1)-mediated oxidative stress signal pathway, and protein inhibitor of activated STATy (PIASy)-mediated apoptosis pathway, leading to the alleviation of oxidative stress and inhibition of apoptosis. These regulative effects of HSAV were further validated by knockdown and overexpression of PKCζ . In conclusion, HSAV showed protective effect against VEI by inhibiting PKCζ and, thereby, ameliorating oxidative stress and inhibiting apoptosis. This study not only provides guidance for the consumption of vinegar in daily life but also promotes the development of diet supplement for disease prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.635232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193096PMC
May 2021

Melatonin Alleviates Contrast-Induced Acute Kidney Injury by Activation of Sirt3.

Oxid Med Cell Longev 2021 25;2021:6668887. Epub 2021 May 25.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

Oxidative stress and apoptosis play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). The purpose of our study was to investigate the protective effects and mechanisms of melatonin against CI-AKI in a CI-AKI mouse model and NRK-52E cells. We established the CI-AKI model in mice, and the animals were pretreated with melatonin (20 mg/kg). Our results demonstrated that melatonin treatment exerted a renoprotective effect by decreasing the level of serum creatinine (SCr) and blood urea nitrogen (BUN), lessening the histological changes of renal tubular injuries, and reducing the expression of neutrophil gelatinase-associated lipid (NGAL), a marker of kidney injury. We also found that pretreatment with melatonin remarkably increased the expression of Sirt3 and decreased the ac-SOD2 K68 level. Consequently, melatonin treatment significantly decreased the oxidative stress by reducing the Nox4, ROS, and malondialdehyde (MDA) content and by increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. The antiapoptotic effect of melatonin on CI-AKI was revealed by decreasing the ratio of Bax/Bcl2 and the cleaved caspase3 level and by reducing the number of apoptosis-positive tubular cells. In addition, melatonin treatment remarkably reduced the inflammatory cytokines of interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor (TGF) in vivo and in vitro. Sirt3 deletion and specific Sirt3 siRNA abolished the above renoprotective effects of melatonin in mice with iohexol-induced acute kidney injury and in NRK-52E cells. Thus, our results demonstrated that melatonin exhibited the renoprotective effects of antioxidative stress, antiapoptosis, and anti-inflammation by the activation of Sirt3 in the CI-AKI model in vivo and in vitro. Melatonin may be a potential drug to ameliorate CI-AKI in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6668887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169261PMC
May 2021

Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices.

Front Cell Dev Biol 2021 21;9:660316. Epub 2021 May 21.

Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.

Activin A, a member of the transforming growth factor-beta (TGF-β) superfamily, contributes to tissue healing and fibrosis. As the innate tissue cells, fibroblasts also play an important role in wound healing and fibrosis. Herein, this study was aimed to investigate how activin A exhibited regulatory effects on adhesion and migration of fibroblasts. We found that activin A induced the migration of fibroblast cell line L929 cells in transwell chamber and microfluidic device. Activin A also promoted L929 cells adhesion, but did not affect L929 cells viability or proliferation. In addition, activin A induced α-SMA expression and TGF-β1 release, which were factors closely related to tissue fibrosis, but had no effect on IL-6 production, a pro-inflammatory cytokine. Furthermore, activin A elevated calcium levels in L929 cells and increased p-ERK protein levels. Activin A-induced migration of L929 cells was attenuated by ERK inhibitor FR180204. To conclude, these data indicated that activin A as a novel chemokine induced the chemotactic migration of L929 cells via ERK signaling and possessed the pro-fibrosis role. These findings provide a new insight into understanding of activin A in tissue fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.660316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175620PMC
May 2021

Pre-emptive pharmacological inhibition of fatty acid-binding protein 4 attenuates kidney fibrosis by reprogramming tubular lipid metabolism.

Cell Death Dis 2021 Jun 3;12(6):572. Epub 2021 Jun 3.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Kidney fibrosis is a hallmark of chronic kidney disease (CKD) progression that is caused by tubular injury and dysregulated lipid metabolism. Genetic abolition fatty acid-binding protein 4 (FABP4), a key lipid transporter, has been reported to suppress kidney interstitial fibrosis. However, the role and underlying mechanism of chemical inhibition of FABP4 in fibrotic kidney have not been well-documented. Here, we examined preemptive the effect of a FABP4 inhibitor, BMS309403, on lipid metabolism of tubular epithelial cells (TECs) and progression of kidney fibrosis. The expression of FABP4 was significantly elevated, concomitated with the accumulation of lipid droplets in TECs during kidney fibrosis. Treatment with BMS309403 alleviated lipid deposition of TECs, as well as interstitial fibrotic responses both in unilateral ureteral obstruction (UUO)-engaged mice and TGF-β-induced TECs. Moreover, BMS309403 administration enhanced fatty acid oxidation (FAO) in TECs by regulating peroxisome proliferator-activated receptor γ (PPARγ) and restoring FAO-related enzyme activities; In addition, BMS309403 markedly reduced cell lipotoxicity, such as endoplasmic reticulum (ER) stress and apoptosis in fibrotic kidney. Taken together, our results suggest that preemptive pharmacological inhibition of FABP4 by BMS309403 rebalances abnormal lipid metabolism in TECs and attenuates the progression of kidney fibrosis, thus may hold therapeutic potential for the treatment of fibrotic kidney diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03850-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175732PMC
June 2021

Iron robbery by intracellular pathogen via bacterial effector-induced ferritinophagy.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210;

Iron is essential for survival and proliferation of an obligatory intracellular bacterium that causes an emerging zoonosis, human monocytic ehrlichiosis. However, how acquires iron in the host cells is poorly understood. Here, we found that native and recombinant (cloned into the genome) translocated factor-3 (Etf-3), a previously predicted effector of the type IV secretion system (T4SS), is secreted into the host cell cytoplasm. Secreted Etf-3 directly bound ferritin light chain with high affinity and induced ferritinophagy by recruiting NCOA4, a cargo receptor that mediates ferritinophagy, a selective form of autophagy, and LC3, an autophagosome biogenesis protein. Etf-3-induced ferritinophagy caused ferritin degradation and significantly increased the labile cellular iron pool, which feeds Indeed, an increase in cellular ferritin by ferric ammonium citrate or overexpression of Etf-3 or NCOA4 enhanced proliferation, whereas knockdown of Etf-3 in via transfection with a plasmid encoding an Etf-3 antisense peptide nucleic acid inhibited proliferation. Excessive ferritinophagy induces the generation of toxic reactive oxygen species (ROS), which could presumably kill both and host cells. However, during proliferation, we observed concomitant up-regulation of Fe-superoxide dismutase, which is an integral component of T4SS operon, and increased mitochondrial Mn-superoxide dismutase by cosecreted T4SS effector Etf-1. Consequently, despite enhanced ferritinophagy, cellular ROS levels were reduced in infected cells compared with uninfected cells. Thus, safely robs host cell iron sequestered in ferritin. Etf-3 is a unique example of a bacterial protein that induces ferritinophagy to facilitate pathogen iron capture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2026598118DOI Listing
June 2021

Samarium-based Grignard-type addition of organohalides to carbonyl compounds under catalysis of CuI.

Chem Commun (Camb) 2021 May 28. Epub 2021 May 28.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.

Grignard-type additions were readily achieved under the mediation of CuI (10 mol%) and samarium (2 equiv.) by employing various organohalides, e.g. benzyl, aryl, heterocyclic and aliphatic halides (Cl, Br or I), and diverse carbonyl compounds (e.g. carbonic esters, carboxylic esters, acid anhydrides, acyl chlorides, ketones, aldehydes, propylene epoxides and formamides) to afford alcohols, ketones and aldehydes, respectively, with high efficiency and chemoselectivity, in which the organosamarium intermediate might be involved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc00965fDOI Listing
May 2021

Circ_0020093 ameliorates IL-1β-induced apoptosis and extracellular matrix degradation of human chondrocytes by upregulating SPRY1 via targeting miR-23b.

Mol Cell Biochem 2021 May 27. Epub 2021 May 27.

Department of Orthopaedics, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Osteoarthritis (OA) is a chronic disease characterized by articular cartilage degeneration and uncontrolled chondrocyte apoptosis. At present, accumulating evidence introduces that circular RNA (circRNA) is involved in the development of OA. The aim of our study was to explore the role and the functional mechanism of circ_0020093 in OA cell model. Human chondrocytes were treated with interleukin-1 beta (IL-1β) to construct OA model. The expression of circ_0020093, miR-23b, and Sprouty 1 (SPRY1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis was assessed by flow cytometry assay. The expression of extracellular matrix (ECM)-associated markers and SPRY1 protein level was detected by qRT-PCR and Western blot. Bioinformatics analysis-predicted relationship between miR-23b and circ_0020093 or SPRY1 was further verified by dual-luciferase reporter assay and RNA pull-down assay. In this study, we found that the expression of circ_0020093 and SPRY1 was declined, while miR-23b expression was elevated in IL-1β-treated chondrocytes. IL-1β induced chondrocyte apoptosis and ECM degradation, while these negative effects were alleviated by circ_0020093 overexpression or miR-23b inhibition. MiR-23b was a target of circ_0020093, and SPRY1 was a downstream target of miR-23b. Rescue experiments showed that miR-23b enrichment reversed the role of circ_0020093 overexpression, and SPRY1 knockdown also reversed the effects of miR-23b inhibition. Importantly, circ_0020093 positively regulated SPRY1 expression by targeting miR-23b. In conclusion, circ_0020093 ameliorates IL-1β-induced apoptosis and ECM degradation of human chondrocytes by regulating the miR-23b/SPRY1 axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-021-04186-2DOI Listing
May 2021

Anemia and Vitamin B-12 and Folate Status in Women of Reproductive Age in Southern India: Estimating Population-Based Risk of Neural Tube Defects.

Curr Dev Nutr 2021 May 26;5(5):nzab069. Epub 2021 Apr 26.

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Women of reproductive age (WRA) are a high-risk population for anemia and micronutrient deficiencies. However, there are few representative population-level data from India, which could help inform evidence-based recommendations and policy.

Objective: To conduct a population-based biomarker survey of anemia and vitamin B-12 and folate status in WRA as part of a periconceptional surveillance program in southern India.

Methods: Participants were WRA (15-40 y) who were not pregnant or lactating. Whole blood (= 979) was analyzed for hemoglobin via a Coulter counter (Coulter HMX). Plasma, serum, and RBCs were processed and stored at -80°C or less until batch analysis. Vitamin B-12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were evaluated via microbiological assay. Anemia and severe anemia were defined as hemoglobin <12.0 g/dL and <8.0 g/dL, respectively. Vitamin B-12 deficiency and insufficiency were defined as total vitamin B-12 <148 pmol/L and <221 pmol/L, respectively. Folate deficiency and insufficiency were defined as RBC folate <305 nmol/L and <748 nmol/L. A previously developed Bayesian model was used to predict neural tube defect (NTD) prevalence per 10,000 births.

Results: A total of 41.5% of WRA had anemia and 3.0% had severe anemia. A total of 48.3% of WRA had vitamin B-12 deficiency and 74.3% had vitamin B-12 insufficiency. The prevalence of RBC folate deficiency was 7.6%, and 79.3% of WRA had RBC folate <748 nmol/L, the threshold for optimal NTD prevention. Predicted NTD prevalence per 10,000 births based on RBC folate concentrations was 20.6 (95% uncertainty interval: 16.5-25.5).

Conclusions: The substantial burden of anemia, vitamin B-12 deficiency, and RBC folate insufficiency in WRA in this setting suggests an opportunity for anemia and birth defects prevention. Findings will directly inform the development of a randomized trial for anemia and birth defects prevention in southern India.This study was registered at clinicaltrials.gov as NCT04048330.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cdn/nzab069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128722PMC
May 2021

Genome-Wide Association Studies-Based Machine Learning for Prediction of Age-Related Macular Degeneration Risk.

Transl Vis Sci Technol 2021 Feb;10(2):29

Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Because age-related macular degeneration (AMD) is a progressive disorder and advanced AMD is currently hard to cure, an accurate and informative prediction of a person's AMD risk using genetic information is desirable for early diagnosis and potential individualized clinical management. The objective of this study was to develop and validate novel prediction models for AMD risk using large genome-wide association studies datasets with different machine learning approaches.

Methods: Genotype data from 32,215 Caucasian individuals with age of ≥50 years from the International AMD Genomics Consortium in dbGaP were used to establish and test prediction models for AMD risk. Four different machine learning approaches-neural network, lasso regression, support vector machine, and random forest-were implemented. A standard logistic regression model using a genetic risk score was also considered.

Results: All machine learning-based methods achieved satisfactory performance for predicting advanced AMD cases (vs. normal controls) (area under the curve = 0.81-0.82, Brier score = 0.17-0.18 in a separate test dataset) and any stage AMD (vs. normal controls) (area under the curve = 0.78-0.79, Brier score = 0.18-0.20 in a separate test dataset). The prediction performance was further validated in an independent dataset of 783 subjects from UK Biobank (area under the curve = 0.67).

Conclusions: By applying multiple state-of-art machine learning approaches on large AMD genome-wide association studies datasets, the predictive models we established can provide an accurate estimation of an individual's AMD risk profile based on genetic information along with age. The online prediction interface is available at: https://yanq.shinyapps.io/no_vs_amd_NN/.

Translational Relevance: The accurate and individualized risk prediction model interface will greatly improve early diagnosis and enhance tailored clinical management of AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.10.2.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900884PMC
February 2021

Calcium Phosphate Cement Causes Nucleus Pulposus Cell Degeneration through the ERK Signaling Pathway.

Open Life Sci 2020 6;15:209-216. Epub 2020 May 6.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006, China.

While calcium phosphate cement (CPC) is recognized as one of the most likely substitutes for the conventional Polymethylmethacrylate (PMMA), there are very few studies about its intradiscal leakage consequences. Herein, the goal of our study was to examine the effect of CPC particles on the ERK (extracellular regulatory kinase) pathway in human nucleus pulposus cell (HNPC) degeneration. Different concentrations of CPC particles (0.00‰, 0.01‰, 0.05‰, 0.1‰ v/v) were added to human nucleus pulposus cell cultures. After 10 days of treatment, HNPC biological behaviors and degeneration degree were analyzed by CCK-8 assay, crystal violet staining, flow cytometer and western blot. The effect of CPC on the ERK pathway was also analyzed by western blot. After activating the ERK path by overexpressing Ras, HNPCs' biological behaviors and degeneration degree were analyzed again. We found that CPC particles had a negative effect on human nucleus pulposus cells (HNPCs), which are mainly reflected in cell growth and the cell cycle. After activation of the ERK signaling pathway, the negative effects of CPC on cell growth and the cell cycle were significantly reduced and the degeneration degree of HNPCs was reversed. CPC particles can probably block the activation of the ERK pathway, thus causing the HNPCs' degeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/biol-2020-0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114789PMC
May 2020

A Case of Phyllodes Tumor of the Breast with Mixed Liposarcoma: Case Report and Literature Review.

Onco Targets Ther 2021 6;14:3003-3011. Epub 2021 May 6.

Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, People's Republic of China.

Phyllodes tumors (PTs) account for less than 1% of breast tumors, and malignant PTs account for even less. Here, we described an unusual case of malignant PT with mixed liposarcoma (myxoid liposarcoma [MLP] and pleomorphic liposarcoma [PLP]). A 52-year-old woman discovered a small lump in her left breast. Twenty years later, the lump suddenly grew within 1 month. Mammography showed space-occupying lesions of the left breast. Histologically, the tumor was characterized by hypercellular stroma covering the epithelium and protrusion of the myoepithelium into the cyst to form a lobulated structure; regions of loose mucus and hypercellular structures alternated. A region of peripheral benign fibroadenoma was also observed, and many stellate and spindle cells or signet ring-like cells were identified in loose areas. Some areas showed a characteristic thin branching vascular pattern. In the cell-rich area, adipocytes and odd megakaryocytes were observed. Atypical mitotic figures were observed in the cell-rich and mucus areas (16 mitoses/10 high-power fields [HPF] and 2 mitoses/10 HPF, respectively). In the immunohistochemical analysis, a small number of tumor cells were positive for AE1/3 and vimentin, whereas all cells were negative for cytokeratin 34βE12, E-cadherin, p63, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and S-100, ruling out the possibility of metaplastic carcinoma. Interestingly, cyclin-dependent kinase 4, mouse double minute 2 (MDM2), and p16 were strongly positive in both loose mucus and cell-rich areas. However, the fluorescence in situ hybridization test results showed that MDM2 was not amplified. Combined with morphological characteristics, these findings supported that the tumor was a mixed malignant PT with MLP and PLP. Our patient did not receive radiation therapy, and after 47 months of follow-up, no recurrence or metastasis occurred. This case report serves to expand the morphologic spectrum of mixed malignant PT with liposarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S298379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110257PMC
May 2021

Efficacy of Selective Vidian Neurectomy for Allergic Rhinitis Combined with Chronic Rhinosinusitis.

ORL J Otorhinolaryngol Relat Spec 2021 May 5:1-8. Epub 2021 May 5.

Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, Beijing, China.

Objective: The aim of this study was to investigate the efficacy of endoscopic selective vidian neurectomy in the treatment of severe persistent allergic rhinitis (AR) combined with chronic rhinosinusitis (CRS) with nasal polyps (ARwCRSwNP).

Methods: One hundred thirty patients with moderate to severe persistent ARwCRSwNP were enrolled at Xuanwu Hospital, Capital Medical University, from September 2015 to September 2017. Patients were divided into 2 groups. Sixty-one patients (the control group) underwent conventional surgical treatment for CRS with nasal polyps and received conservative treatment for AR. Sixty-nine patients (the experimental group) received conventional surgical treatment for CRS with nasal polyps plus endoscopic selective vidian neurectomy with amputation of the posterior nasal nerve and pharyngeal branch of the vidian nerve. Clinical parameters, including visual analog scale (VAS) score, Lund-Kennedy endoscopic mucosal morphology score, and Lund-Mackay sinus computed tomography (CT) scan lesion range score, were used to analyze and evaluate the preoperative and postoperative data. Comparisons were based on patient scores, and preoperative and postoperative scores obtained at 6, 12, and 24 months were analyzed.

Results: The experimental group had higher therapeutic efficacy in nasal obstruction, nasal itching, rhinorrhea, sneezing, and general symptoms than the control group (p < 0.05). No complications such as tear-secretion disorder or atrophic rhinitis occurred in the experimental group, and no significant difference in complications incidence was observed between the 2 groups (p > 0.05).

Conclusion: Endoscopic selective vidian neurectomy is an effective and safe technique for the management of moderate to severe persistent ARwCRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512083DOI Listing
May 2021

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease.

Front Neurol 2021 15;12:595984. Epub 2021 Apr 15.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.595984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081882PMC
April 2021

Survival and transcriptomic response of Salmonella enterica on fresh-cut fruits.

Int J Food Microbiol 2021 Jun 20;348:109201. Epub 2021 Apr 20.

Department of Food Science and Nutrition & Institute for Food Safety and Health, Illinois Institute of Technology, Bedford Park, IL, USA.

Salmonella enterica is frequently implicated in foodborne disease outbreaks associated with fresh-cut fruits. In the U.S., more than one third of fruit-related outbreaks have been linked to two S. enterica serotypes Newport and Typhimurium. Approximately 80% of fruit-related human salmonellosis cases were associated with tomatoes, cantaloupes and cucumbers. In this study, we investigated the population dynamics of S. Newport and S. Typhimurium on fresh-cut tomato, cantaloupe, cucumber and apple under short-term storage conditions. We further compared the transcriptomic profiles of a S. Newport strain on fresh-cut tomato and cantaloupe using high-throughput RNA-seq. We demonstrated that both S. enterica Newport and Typhimurium survived well on various fresh-cut fruit items under refrigeration storage conditions, independent of inoculation levels. However, S. enterica displayed variable survival behaviors on different types of fruits. For example, at 7 d storage, the population of S. enterica reduced less than 0.2 log (p > 0.05) on fresh-cut tomato and cantaloupe, in contrast to ~0.5 log (p < 0.05) on cucumber and apple. RNA-seq analysis suggested that S. enterica mediates its survival on fresh-cut fruits through differentially regulating genes involved in specific carbon utilization and metabolic pathways. Several known bacterial virulence factors (e.g., pag gene) were found to be differentially regulated on fresh-cut tomato and cantaloupe, suggesting a link between the events of food contamination and subsequent human infection. Findings from this study contribute to a better understanding of S. enterica survival mechanisms on fresh-cut produce.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109201DOI Listing
June 2021

Impact of Voluntary Folic Acid Fortification of Corn Masa Flour on RBC Folate Concentrations in the U.S. (NHANES 2011-2018).

Nutrients 2021 Apr 16;13(4). Epub 2021 Apr 16.

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, GA 30341, USA.

Surveillance data have highlighted continued disparities in neural tube defects (NTDs) by race-ethnicity in the United States. Starting in 2016, the Food and Drug Administration (FDA) authorized voluntary folic acid fortification of corn masa flour to reduce the risk of neural tube defects (NTDs) among infants of Hispanic women of reproductive age. To assess the impact of voluntary corn masa fortification, cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 for Hispanic women of reproductive age with available red blood cell (RBC) folate concentrations were analyzed, with additional analyses conducted among Hispanic women whose sole source of folic acid intake was fortified foods (enriched cereal grain products (ECGP) only), excluding ready-to-eat cereals and supplements. RBC folate concentration (adjusted geometric mean) among Hispanic women of reproductive age did not differ between 2011-2016 and 2017-2018, though RBC folate concentration increased significantly among lesser acculturated Hispanic women consuming ECGP only. Concentrations of RBC folate for those born outside the U.S and residing in the U.S <15 years increased from 894 nmol/L (95% CI: 844-946) in 2011-2016 to 1018 nmol/L (95% CI: 982-1162; < 0.001) in 2017-2018. Primarily Spanish-speaking Hispanic women of reproductive age who only consumed ECGP saw an increase from 941 nmol/L (95% CI: 895-990) in 2011-2016 to 1034 nmol/L (95% CI: 966-1107; = 0.03) in 2017-2018. By subpopulation, we observed no significant changes in the proportion at risk of NTDs (<748 nmol/L) and no changes in the model-based estimated NTD rates following voluntary corn masa fortification. This analysis suggests that there is a remaining risk among Hispanics for folate sensitive NTDs, though continued monitoring of folate status in future NHANES data cycles will help inform the long-term efficacy of voluntary fortification of corn masa flour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13041325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073626PMC
April 2021

Genome-Wide Analysis and Expression Profiles of the Dof Family in under Temperature, Salt and ABA Treatment.

Plants (Basel) 2021 Apr 23;10(5). Epub 2021 Apr 23.

The State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.

The DNA-binding with one zinc finger () family of plant-specific transcription factors has a variety of important functions in gene transcriptional regulation, development, and stress responses. However, the structure and expression patterns of family have not been identified in , which is an important xerophytic and perennial gramineous grass in desert grassland. In this study, 50 genes were identified in and could be classified into four groups. According to genome-wide analysis, 46 of 50 genes were located on 20 chromosomes, and the gene structure and conserved protein motif of these proteins were analyzed. In addition, phylogenetic analysis of genes in , , , and estimated the evolutionary relationships, and these genes were grouped into seven clusters. Moreover, the expression profiles of these genes in were analyzed in response to high/low temperature, salinity, and ABA treatments. These results will provide valuable information for future studies on gene classification, cloning, and functional characterization of this family in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants10050850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146245PMC
April 2021

High-Resolution Metabolomic Assessment of Pesticide Exposure in Central Valley, California.

Chem Res Toxicol 2021 May 29;34(5):1337-1347. Epub 2021 Apr 29.

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California 90095, United States.

Pesticides are widely used in the agricultural Central Valley region of California. Historically, this has included organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs). This study aimed to identify perturbations of the serum metabolome in response to each class of pesticide and mutual associations between groups of metabolites and multiple pesticides. We conducted high-resolution metabolomic profiling of serum samples from 176 older adults living in the California Central Valley using liquid chromatography with high-resolution mass spectrometry. We estimated chronic pesticide exposure (from 1974 to year of blood draw) to OPs, OCs, and PYRs from ambient sources at homes and workplaces with a geographic information system (GIS)-based model. Based on partial least-squares regression and pathway enrichment analysis, we identified metabolites and metabolic pathways associated with one or multiple pesticide classes, including mitochondrial energy metabolism, fatty acid and lipid metabolism, and amino acid metabolism. Utilizing an integrative network approach, we found that the fatty acid β-oxidation pathway is a common pathway shared across all three pesticide classes. The disruptions of the serum metabolome suggested that chronic pesticide exposure might result in oxidative stress, inflammatory reactions, and mitochondrial dysfunction, all of which have been previously implicated in a wide variety of diseases. Overall, our findings provided a comprehensive view of the molecular mechanisms of chronic pesticide toxicity, and, for the first time, our approach informs exposome research by moving from macrolevel population exposures to microlevel biologic responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrestox.0c00523DOI Listing
May 2021

An intracellular nanobody targeting T4SS effector inhibits infection.

Proc Natl Acad Sci U S A 2021 May;118(18)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210;

Infection with obligatory intracellular bacteria is difficult to treat, as intracellular targets and delivery methods of therapeutics are not well known. translocated factor-1 (Etf-1), a type IV secretion system (T4SS) effector, is a primary virulence factor for an obligatory intracellular bacterium, In this study, we developed Etf-1-specific nanobodies (Nbs) by immunizing a llama to determine if intracellular Nbs block Etf-1 functions and infection. Of 24 distinct anti-Etf-1 Nbs, NbD7 blocked mitochondrial localization of Etf-1-GFP in cotransfected cells. NbD7 and control Nb (NbD3) bound to different regions of Etf-1. Size-exclusion chromatography showed that the NbD7 and Etf-1 complex was more stable than the NbD3 and Etf-1 complex. Intracellular expression of NbD7 inhibited three activities of Etf-1 and : up-regulation of mitochondrial manganese superoxide dismutase, reduction of intracellular reactive oxygen species, and inhibition of cellular apoptosis. Consequently, intracellular NbD7 inhibited infection, whereas NbD3 did not. To safely and effectively deliver Nbs into the host cell cytoplasm, NbD7 was conjugated to cyclized cell-permeable peptide 12 (CPP12-NbD7). CPP12-NbD7 effectively entered mammalian cells and abrogated the blockade of cellular apoptosis caused by and inhibited infection by in cell culture and in a severe combined-immunodeficiency mouse model. Our results demonstrate the development of an Nb that interferes with T4SS effector functions and intracellular pathogen infection, along with an intracellular delivery method for this Nb. This strategy should overcome current barriers to advance mechanistic research and develop therapies complementary or alternative to the current broad-spectrum antibiotic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2024102118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106314PMC
May 2021

Ang II Promotes SUMO2/3 Modification of RhoGDI1 Through Aos1 and Uba2 Subunits, and then Regulates RhoGDI1 Stability and Cell Proliferation.

Cardiovasc Drugs Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Pharmacology, School of pharmacy, Nantong University, 19 QiXiu Road, Nantong, 226001, Jiangsu, China.

Purpose: Ang II regulates RhoGDI1 stability and cell proliferation via SUMOylation. However, how Ang II regulates RhoGDI1 SUMOylation remains unknown. In this study, we focused on revealing the effects of E1 subunits (Aos1 and Uba2) on RhoGDI1 SUMOylation in HA-VSMC proliferation.

Methods: The expressions of Aos1, Uba2, and SUMO1 were suppressed by siRNA transfection. HA-VSMCs were treated with Ang II (100 nM) for 24 h. RhoGDI1 SUMOylation and ubiquitination were checked by co-immunoprecipitation. Cell proliferation was detected by EdU assay.

Results: Uba2 or Aos1 suppression significantly inhibited Ang II-induced SUMO2/3 modification of RhoGDI1 and cell proliferation, while not affecting SUMO1 modification of RhoGDI1. In addition, Uba2 or Aos1 suppression promoted RhoGDI1 ubiquitination and degradation. These indicate that both Uba2 and Aos1 are necessary for SUMO2/3 modification of RhoGDI1 that participates in cell proliferation by regulating RhoGDI1 ubiquitination and stability. Moreover, SUMO1 suppression did not affect RhoGDI1 ubiquitination and degradation and cell proliferation in Ang II-induced VSMCs, suggesting that SUMO1 modification does not participate in RhoGDI1 stability and cell proliferation.

Conclusion: This study reveals the differences between SUMO2/3 and SUMO1 modification in regulating RhoGDI1 stability and Ang II-mediated cell proliferation. Schematic summary of roles of SUMO1 and SUMO2/3 modification of RhoGDI1 in regulating RhoGDI1 stability and cell proliferation in Ang II-treated HA-VSMCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-021-07173-3DOI Listing
April 2021

Differential Diagnosis Strategy between Lower Extremity Arterial Occlusive Disease and Lumbar Disc Herniation.

Biomed Res Int 2021 5;2021:6653579. Epub 2021 Apr 5.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Considering the increasingly incidence rate of lower extremity arterial occlusive disease and difficult to distinguish from lumbar disc herniation, it is very necessary to exclude lower extremity arterial occlusive disease resulting in lower limb symptoms from lumbar disc herniation. More importantly, who have a higher risk of combining with lower extremity arterial occlusive disease and misdiagnosed as lumbar disc herniation? Why those patients are easy to be misdiagnosed as lumbar disc herniation? It is worth analyzing and discussing. The risk factors including age, gender, the medical history of high blood pressure, diabetes, smoking and coronary, pulse pressure, lumbar disc herniation segment and type, ankle-brachial index, and straight leg raising test were observed. The Oswestry disability index and the Japanese Orthopedic Association score were collected preoperative, six months after posterior lumbar interbody fusion and six months after vascular interventional treatment to evaluate the symptoms relief and surgical efficacy. There was a statistically significant difference ( < 0.01) in pulse pressure, ankle-brachial index, central disc herniation, and straight leg raising test between two groups. There was a high risk to missed diagnosis of lower extremity arterial occlusive disease and misdiagnosed as lumbar disc herniation when patients are with a mild central lumbar disc herniation, higher pulse pressure, lower ankle-brachial index, and straight leg raising test negative. Therefore, sufficient history-taking and cautious physical examinations contributed to find risk factors and attach importance to such patients and, further, to exclude lower extremity arterial occlusive disease from lumbar disc herniation using lower extremity vascular ultrasound examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6653579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041544PMC
May 2021

Targeted gene panel sequencing for molecular diagnosis of congenital adrenal hyperplasia.

J Steroid Biochem Mol Biol 2021 Jul 14;211:105899. Epub 2021 Apr 14.

Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai, 200025, PR China. Electronic address:

Context: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic diseases caused by genetic deficiency in nine genes encoding steroidogenesis enzymes and cofactors.

Objective: To establish a targeted next-generation sequencing (NGS) assay for all nine CAH candidate genes.

Methods: We developed a customized targeted NGS assay of CAH candidate genes (CYP21A2, CYP17A1, CYP11B1, StAR, CYP11A1, POR, HSD3B2, H6PD, CYP11B2) and apply this assay plus MLPA of CYP21A2 in a total of 469 patients with CAH like signs and symptoms.

Results: We totally identified 125 variants with seven variant types in eight genes. Variant types included missense variant (46.8 %), splicing variant (21.5 %), small indel (12.5 %), large structure variation (11.8 %), nonsense variant (4.1 %), UTR variant (2.9 %), synonymous variant (0.3 %). Successful genotyping, defined as biallelic pathogenic or likely pathogenic variants, was achieved in 98.5 % (336/341) of cases, including biallelic variants in CYP21A2 (n = 254), CYP17A1 (n = 45), CYP11B1 (n = 23), StAR (n = 7), HSD3B2 (n = 4), POR (n = 1), CYP11A1 (n = 1) and CYP11B2 (n = 1) gene. Importantly, the assay found one patient with CYP11B1 deficiency, one patient with non-classic POR deficiency and two patients with non-classic CYP17A1 deficiency while clinically diagnosed differently.

Conclusions: Our NGS-based assay plus MLPA of CYP21A2 is a useful tool to genotype all subtypes of CAH. The test successfully achieved genotype in 98.5 % of patients with clinically determined CAH. It also efficiently facilitated the diagnosis of CAH in patients with rare subtypes as well as non-classic phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsbmb.2021.105899DOI Listing
July 2021

High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

Cell Rep 2021 Apr;35(2):108974

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4 innate immune cells and another dominated by interferon (IFN)-γ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10 macrophages. To better understand cellular mediators of severe asthma, we developed the Immune Cell Linkage through Exploratory Matrices (ICLite) algorithm to perform deconvolution of bulk RNA sequencing of mixed-cell populations. Signatures of mitosis and IL-7 signaling in CD206FcεRICD127IL-4 innate cells in one patient group, contrasting with adaptive immune response in T cells in the other, are preserved across technologies. Transcriptional signatures uncovered by ICLite identify T-cell-high and T-cell-poor severe asthma patients in an independent cohort, suggesting broad applicability of our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.108974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133874PMC
April 2021

The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma.

Pathol Res Pract 2021 Jun 24;222:153416. Epub 2021 Mar 24.

Department of Pathology, Shihezi University School of Medicine & the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China; Department of Pathology, Central People's Hospital of Zhanjiang and Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, China. Electronic address:

Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2021.153416DOI Listing
June 2021

AMD Genetics: Methods and Analyses for Association, Progression, and Prediction.

Adv Exp Med Biol 2021 ;1256:191-200

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.

Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease, which is a leading cause of vision loss among the elderly in the developed countries. As one of the most successful examples of genome-wide association study (GWAS), a large number of genetic studies have been conducted to explore the genetic basis for AMD and its progression, of which over 30 loci were identified and confirmed. In this chapter, we review the recent development and findings of GWAS for AMD risk and progression. Then, we present emerging methods and models for predicting AMD development or its progression using large-scale genetic data. Finally, we discuss a set of novel statistical and analytical methods that were recently developed to tackle the challenges such as analyzing bilateral correlated eye-level outcomes that are subject to censoring with high-dimensional genetic data. Future directions for analytical studies of AMD genetics are also proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-66014-7_7DOI Listing
April 2021

Effect of anesthesia on electrocorticography for localization of epileptic focus: Literature review and future directions.

Epilepsy Behav 2021 05 2;118:107902. Epub 2021 Apr 2.

Comprehensive Epilepsy Center, Dept. of Neurology, School of Medicine, Yale University, Yale New Haven Hospital, New Haven, CT, United States; Human Brain Mapping Program, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.

Intraoperative electrocorticography (ECoG) is a useful technique to guide resections in epilepsy surgery and is mostly performed under general anesthesia. In this systematic literature review, we seek to investigate the effect of anesthetic agents on the quality and reliability of ECoG for localization of the epileptic focus. We conducted a systematic search using PubMed and EMBASE until January 2019, aiming to review the effects of anesthesia on ECoG yield. Fifty-eight studies were included from 1016 reviewed. There are favorable reports for dexmedetomidine and remifentanil during ECoG recording. There is inadequate, or sometimes conflicting, evidence to support using enflurane, isoflurane, sevoflurane, and propofol. There is evidence to avoid halothane, nitrous oxide, etomidate, ketamine, thiopental, methohexital, midazolam, fentanyl, and alfentanil due to undesired effects. Depth of anesthesia, intraoperative awareness, and surgical outcomes were not consistently evaluated. Available studies provide helpful information about the effect of anesthesia on ECoG to localize the epileptic focus. The proper use of anesthetic agents and careful dose titration, and effective communication between the neurophysiologist and anesthesiologist based on ECoG activity are essential in optimizing recordings. Anesthesia is a crucial variate to consider in the design of studies investigating ECoG and related biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.107902DOI Listing
May 2021

RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells.

Front Cell Dev Biol 2021 18;9:634902. Epub 2021 Mar 18.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

The therapeutic approach of liver fibrosis is still an unsolved clinical problem worldwide. Notably, the accumulation of extracellular matrix (ECM) in the liver is mediated by the production of cytokines and growth factors, such as transforming growth factor-β1 (TGF-β1) in hepatic stellate cells (HSCs). Ring finger protein 2 (RNF2) was identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), mediating the monoubiquitination of histone H2A. In recent years, a growing amount of evidence suggests that RNF2 may play an important role in multiple pathological processes involved in cancer. Here, we explored the role of RNF2 in liver fibrogenesis and its potential mechanisms. The results showed that RNF2 was up-regulated in human fibrotic liver tissue. Knockdown of RNF2 led to a decreasing expression of collagen1 and α-smooth muscle actin (α-SMA) in LX-2 cells, which was upregulated by RNF2 overexpression. Moreover, RNF2 overexpression significantly promoted TGF-β1-induced LX-2 cell proliferation but decreased apoptosis. Furthermore, knockdown of RNF2 inhibited the activation of ERK/p38 signaling pathways induced by TGF-β1. These data suggested that RNF2 is an effective pro-fibrogenic factor for HSC activation via ERK/p38 signaling pathway. RNF2 inhibition might be a promising therapeutic target for liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.634902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015948PMC
March 2021

Split-thickness skin graft donor-site morbidity: A systematic literature review.

Burns 2021 Feb 25. Epub 2021 Feb 25.

Shriners Hospital for Children-Boston, 51 Blossom Street, Suite 930, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02114, USA; Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.

The purpose of this systematic literature review is to critically evaluate split-thickness skin graft (STSG) donor-site morbidities. The search of peer-reviewed articles in three databases from January 2009 to July 2019 identified 4271 English-language publications reporting STSG donor-site clinical outcomes, complications, or quality of life. Of these studies, 77 met inclusion criteria for analysis. Mean time to donor-site epithelialization ranged from 4.7 to 35.0 days. Mean pain scores (0-10 scale) ranged from 1.24 to 6.38 on postoperative Day 3. Mean scar scores (0-13 scale) ranged from 0 to 10.9 at Year 1. One study reported 28% of patients had donor-site scar hypertrophy at 8 years. Infection rates were generally low but ranged from 0 to 56%. Less frequently reported outcomes included pruritus, wound exudation, and esthetic dissatisfaction. Donor-site wounds underwent days of wound care and were frequently associated with pain and scarring. Widespread variations were noted in STSG donor-site outcomes likely due to inconsistencies in the definition of outcomes and utilization of various assessment tools. Understanding the true burden of donor sites may drive innovative treatments that would reduce the use of STSGs and address the associated morbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.burns.2021.02.014DOI Listing
February 2021

State-Temporal Compression in Reinforcement Learning with the Reward-Restricted Geodesic Metric.

IEEE Trans Pattern Anal Mach Intell 2021 Mar 25;PP. Epub 2021 Mar 25.

It is difficult to solve complex tasks that involve large state spaces and long-term decision processes by reinforcement learning (RL) algorithms. A common and promising method to address this challenge is to compress a large RL problem into a small one. Towards this goal, the compression should be state-temporal and optimality-preserving (i.e., the optimal policy of the compressed problem should correspond to that of the uncompressed problem). In this paper, we propose a reward-restricted geodesic (RRG) metric, which can be learned by a neural network, to perform state-temporal compression in RL. We prove that compression based on the RRG metric is approximately optimality-preserving for the raw RL problem endowed with temporally abstract actions. With this compression, we design an RRG metric-based reinforcement learning (RRG-RL) algorithm to solve complex tasks. Experiments in both discrete (2D Minecraft) and continuous (Doom) environments demonstrated the superiority of our method over existing RL approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TPAMI.2021.3069005DOI Listing
March 2021

Synergistic Inhibition of Drug-Resistant Colon Cancer Growth with PI3K/mTOR Dual Inhibitor BEZ235 and Nano-Emulsioned Paclitaxel via Reducing Multidrug Resistance and Promoting Apoptosis.

Int J Nanomedicine 2021 15;16:2173-2186. Epub 2021 Mar 15.

Department of Pathology, The First Affiliated Hospital, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases of the Ministry of Education of China, Xinjiang, 832002, People's Republic of China.

Background: Colon cancer is a top lethal cancer in man and women worldwide and drug resistance is the major cause of cancer-related death. Combinational therapy and drug delivery with nanoparticles have been shown to effectively overcome drug resistance in many cancers. We previously reported that nanoemulsion (NE) loaded paclitaxel (PTX) and BEZ235 could synergistically inhibit colon cancer cell growth.

Purpose: To investigate whether NE loaded PTX and BEZ235 can overcome drug resistance and synergistically inhibit drug-resistant colon cancer cell growth in vitro and in vivo.

Methods: The in vitro treatment effect on cell viability was assayed using CCK8 kit, cell morphological change was detected by β-tubulin immunofluorescence staining, drug resistance-related proteins were analyzed by Western blotting, and in vivo tumor growth test was performed in nude mice xeno-transplanted with 2 drug-resistant colon cancer cell lines HCT116-LOHP and HT29-DDP.

Results: Both cell lines were sensitive to PTX but relatively insensitive to BEZ235. PTX combined with BEZ235 synergistically inhibited the proliferation of both cell lines. Nanoemulsion loaded PTX (NE-PTX) reduced the IC50 of PTX to approximately 2/5 of free PTX, indicating a high inhibitory efficacy of NE-PTX. When NE-PTX combined with a low concentration of BEZ235 (50 nM), the IC50 was decreased to approximately 2/3 of free PTX. Moreover, NE-PTX+BEZ235 treatment increased apoptosis, decreased Pgp and ABCC1 expression, and reduced tumor weights compared to the single drug treatment and the control group. These results suggest that nanoemulsion loaded PTX+BEZ235 can overcome drug resistance and improve the inhibitory effect on cancer cell proliferation and tumor growth.

Conclusion: Our study thus provides a possible new approach to treat colon cancer patients with drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S290731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979685PMC
April 2021

A region-based method for causal mediation analysis of DNA methylation data.

Epigenetics 2021 03 23:1-11. Epub 2021 Mar 23.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Exposure to environmental factors can affect DNA methylation at a 5'-cytosine-phosphate-guanine-3' (CpG) site or a genomic region, which can then affect an outcome. In other words, environmental effects on an outcome could be mediated by DNA methylation. To date, single CpG-site-based mediation analysis has been employed extensively. More recently, however, there has been considerable interest in studying differentially methylated regions (DMRs), both because DMRs are more likely to have functional effects than single CpG sites and because testing DMRs reduces multiple testing. In this report, we propose a novel causal mediation approach under the counterfactual framework to test the significance of total (TE), direct (DE), and indirect effects (IE) of predictors on response variable with a methylated region (MR) as the mediator (denoted as MR-Mediation). Functional linear transformation is used to reduce the possible high dimension of the CpG sites in a predefined MR and to account for their location information. In our simulation studies, MR-Mediation retained the desired Type I error rates for TE, DE, and IE tests. Furthermore, MR-Mediation had better power performance than testing mean methylation level as the mediator in most considered scenarios, especially for IE (i.e., mediated effect) test, which could be more interesting than the other two effect tests. We further illustrate our proposed method by analysing the methylation mediated effect of exposure to gun violence on total immunoglobulin E or atopic asthma among participants in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2021.1900026DOI Listing
March 2021