Publications by authors named "Yu Lei"

1,886 Publications

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Prognostic factors of chondroblastic osteosarcoma and nomogram development for prediction: A population-based, STROBE-compliant study.

Medicine (Baltimore) 2021 Jun;100(23):e26021

Department of Orthopedics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract: The present study aimed to develop nomograms to predict survival in patients with chondroblastic osteosarcoma (COS).An analysis was conducted of 320 cases of COS collected from the surveillance, epidemiology, and end results (SEER) database between 2004 and 2015. Independent prognostic factors were screened using univariate and multivariate Cox analyses. Subsequently, nomograms were established to predict the patients' cancer-specific survival (CSS) and overall survival (OS) rates. The prediction accuracy and discriminative ability of the nomograms were examined using calibration curves and the concordance index (C-index).As revealed in the univariate and multivariate Cox regression analysis, age, tumor size, the primary site, the presence of metastasis, a history of having undergone surgery, and a history of having received radiotherapy were found to be independent prognostic factors associated with survival in patients with COS (all P < .05). Furthermore, age >39 years, the presence of distant metastasis, no history of having undergone any surgery, and tumor size >103 mm were found to be associated with poor prognosis in patients, while the primary site of the mandible and no history of having undergone radiotherapy showed associations with a more favorable prognosis in patients. Next, nomograms were constructed to predict the OS and CSS in patients with COS.We constructed nomograms that can provide accurate survival predictions in patients with chondroblastic osteosarcoma. These nomograms can help surgeons customize the treatment strategies for patients with chondroblastic osteosarcoma.
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http://dx.doi.org/10.1097/MD.0000000000026021DOI Listing
June 2021

A Prospective Investigation of Bispecific CD19/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Front Oncol 2021 25;11:664421. Epub 2021 May 25.

Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: The use of T cells expressing chimeric antigen receptor (CAR T) engineered to target CD19 constitutes breakthrough treatment for relapsed or refractory B cell non-Hodgkin lymphoma (R/R B-NHL). Despite improved outcomes, high relapse rate remains a challenge to overcome. Here, we report the clinical results and the pharmacokinetics of bispecific CD19/22 CAR T in patients with R/R B-NHL.

Methods: We performed a prospective, single-arm study of bispecific CD19/22 CAR T cells in R/R B-NHL. We analyzed the safety and efficacy and investigated the kinetic profiles of the CAR T cells. CAR transgene levels were measured using quantitative polymerase chain reaction, and correlation analyses of pharmacodynamic markers and product characteristics, disease conditions, clinical efficacy and adverse events were performed.

Results: From August 2017 to September 2020, a total of 32 patients with CD19/22 CAR T administration were analyzed. The overall response rate was 79.3%, and the complete response rate was 34.5%. The progression-free survival (PFS) and overall survival (OS) rates at 12 months were 40.0% and 63.3%, respectively. Among patients who had a CR at 3 months, the PFS and OS rates at 12 months were 66.7% and 100%, respectively. Severe cytokine release syndrome (sCRS) (grade 3 and higher) occurred in nine patients (28.1%). Grade 3 or higher neurologic events occurred in four patients (12.5%). One patient died from irreversible severe CRS-associated acute kidney injury. Long-term CAR T cells persistence correlated with clinical efficacy (133 days vs 22 days, P = 0.004). Patients treated with more than three prior therapies and presenting extranodal organ involvement had lower maximal concentration (C) values than other patients. Responders had higher C and area under the curve values than non-responders. Tumour burden and C were potentially associated with the severity of CRS.

Conclusions: This study demonstrates the safety and potential clinical efficacy of bispecific CD19/22 CAR T cells in patients with R/R B-NHL and highlights the importance of measuring kinetic parameters in PB to predict efficacy and safety in clinical applications of CAR T cell therapy.

Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.
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http://dx.doi.org/10.3389/fonc.2021.664421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185372PMC
May 2021

High electrochemical performance of Ni-foam supported TiCTMXene/rGO nanocomposite.

Nanotechnology 2021 Jun 8. Epub 2021 Jun 8.

Minjiang University, Xiyuangong Road 200 , Shangjie Town, Minhou County, Fuzhou City, PR China, Fuzhou, 350108, CHINA.

Two-dimensional (2D) materials have attracted extensive attention owing to their unique electronic/physiochemical properties, and wide application potential in energy storage and conversion. However, 2D materials are often tendency to aggregate due to the strong van der Waals interactions, leading to gradually decrease of an efficient mass transfer pathway and accessible surface area for the electrolyte. Here, we demonstrate an efficient approach for large-scale production of a hybrid nanostructures (TiCT/rGO) based on ultrathin MXene nanosheets anchored on layered reduced graphene (rGO) supported by porous Ni-foam via a plain chemical dipping-method followed by high temperature annealing process. TiCT/rGO electrode exhibits a porous structure, excellent ionic and electrical conductivities, and remarkable specific capacitance. Furthermore, it shows ultra-high cycle stability, for example, 88.70% of its specific capacity can be maintained through 3000 cycles. This kind of porous nanostructure and integrated design idea is significant to design other energy storage modules.
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http://dx.doi.org/10.1088/1361-6528/ac0934DOI Listing
June 2021

Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling.

Cell Mol Biol Lett 2021 Jun 7;26(1):26. Epub 2021 Jun 7.

Department of General Surgery, First Affiliated Hospital of China Medical University, Liaoning Province Shenyang City Heping District Nanjingbei Road 155, Shenyang, 110001, Liaoning, People's Republic of China.

Background: Currently, resistance against cisplatin (DDP) is a frequent problem for the success of advanced gastric carcinoma (GC) chemotherapy. Here, we sought to investigate the function of activating transcription factor 3 (ATF3) n GC chemoresistance.

Methods: Expression of ATF3 was determined in GC cell lines (MNK45, SGC7901, and BGC823) and cisplatin (DDP)-resistant cells (SGC7901/DDP and BGC823/DDP). Biological informatics was performed to analyze ATF3 expression and prognosis in GC patients. Cisplatin resistance was evaluated. Ferroptosis was detected after ATF3 transfection of cells. The underlying molecular mechanism was also investigated.

Results: Transcripts of ATF3 were decreased in GC cells and GC tissues. Kaplan-Meier plotter analysis revealed that ATF3 expression was positively related to the overall survival of GC patients. In particular, lower levels of ATF3 were observed in cisplatin-resistant SGC7901/DDP and BGC823/DDP relative to their parental cells. Notably, ATF3 elevation sensitized cisplatin-resistant cells to cisplatin. Mechanically, compared with parental cells, SGC7901/DDP and BGC823/DDP cells exhibited lower ferroptosis evident by lower ROS, MDA and lipid peroxidation and higher intracellular GSH levels. However, ATF3 elevated ferroptosis in SGC7901/DDP and BGC823/DDP cells. Intriguingly, ATF3 overexpression together with ferroptosis activator erastin or RSL3 treatment further enhanced ferroptosis and cisplatin resistance; however, the ferroptosis suppressor liproxstatin-1 reversed the function of ATF3 in ferroptosis and cisplatin resistance. Additionally, cisplatin-resistant cells exhibited stronger activation of Nrf2/Keap1/xCT signaling relative to parental cells, which was restrained by ATF3 up-regulation. Importantly, restoring Nrf2 signaling overturned ATF3-mediated ferroptosis and cisplatin resistance.

Conclusion: ATF3 may sensitize GC cells to cisplatin by induction of ferroptosis via blocking Nrf2/Keap1/xCT signaling, supporting a promising therapeutic approach for overcoming chemoresistance in GC.
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http://dx.doi.org/10.1186/s11658-021-00271-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186082PMC
June 2021

Machine learning-assisted immune profiling stratifies peri-implantitis patients with unique microbial colonization and clinical outcomes.

Theranostics 2021 3;11(14):6703-6716. Epub 2021 May 3.

Department of Periodontics and Oral Medicine, the University of Michigan School of Dentistry, Ann Arbor, MI 48109.

The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution. Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. and were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization. Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis.
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http://dx.doi.org/10.7150/thno.57775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171076PMC
May 2021

Rhein attenuates PTZ‑induced epilepsy and exerts neuroprotective activity via inhibition of the TLR4-NFκB signaling pathway.

Neurosci Lett 2021 Jun 3:136002. Epub 2021 Jun 3.

Department of basic medicine, Xi'an Medical University, Xi'an, Shaanxi, China. Electronic address:

Background: Epilepsy is a common neurological disease that cannot be well controlled by existing antiepileptic drugs. Studies have implicated oxidative stress and inflammation in the pathophysiology of epilepsy. Rhein has a comprehensive pharmacological function in reducing inflammation and can play a neuroprotective role in many neurological diseases, however little is known about its effects on epilepsy.

Methods: A model of acute epilepsy in mice was established using the Pentylenetetrazol (PTZ) ignition method to evaluate the effects of Rhein on the duration and latency of convulsions, and the number and severity of seizures. Modified Neurological Severity Score (mNSS), Rotarod and open-field behavioral task tests were performed to evaluate the neuroprotective effect of Rhein. TUNEL staining was used to assess neuronal damage, and western blot, qPCR and ELISA kits were utilized to determine the expression of inflammatory signaling protein molecules and levels of inflammatory cytokines.

Results: In this study, we demonstrate that Rhein delayed the onset of seizures, decreased their severity, and reduced the duration and frequency of seizures in PTZ-induced epileptic mice. Furthermore, we found that Rhein blocked neurological deficits induced by PTZ. In addition, our results show that Rhein inhibited the activation of the TLR4-NFκB signaling pathway and decreased the secretion of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18.

Conclusion: Our results suggest that the anticonvulsant and neuroprotective effects of Rhein are achieved by disrupting the processes involved in PTZ acquisition of epilepsy.
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http://dx.doi.org/10.1016/j.neulet.2021.136002DOI Listing
June 2021

The effect of methanol fixation on single-cell RNA sequencing data.

BMC Genomics 2021 Jun 5;22(1):420. Epub 2021 Jun 5.

Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.

Background: Single-cell RNA sequencing (scRNA-seq) has led to remarkable progress in our understanding of tissue heterogeneity in health and disease. Recently, the need for scRNA-seq sample fixation has emerged in many scenarios, such as when samples need long-term transportation, or when experiments need to be temporally synchronized. Methanol fixation is a simple and gentle method that has been routinely applied in scRNA-sEq. Yet, concerns remain that fixation may result in biases which may change the RNA-seq outcome.

Results: We adapted an existing methanol fixation protocol and performed scRNA-seq on both live and methanol fixed cells. Analyses of the results show methanol fixation can faithfully preserve biological related signals, while the discrepancy caused by fixation is subtle and relevant to library construction methods. By grouping transcripts based on their lengths and GC content, we find that transcripts with different features are affected by fixation to different degrees in full-length sequencing data, while the effect is alleviated in Drop-seq result.

Conclusions: Our deep analysis reveals the effects of methanol fixation on sample RNA integrity and elucidates the potential consequences of using fixation in various scRNA-seq experiment designs.
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http://dx.doi.org/10.1186/s12864-021-07744-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180132PMC
June 2021

Association of Lewy Bodies With Age-Related Clinical Characteristics in Black and White Decedents.

Neurology 2021 Jun 4. Epub 2021 Jun 4.

Department of Neurological Sciences, Rush Alzheimer Disease Center and Rush University Medical Center.

Objective: The associations of Lewy bodies (LBs) with olfactory dysfunction, parkinsonism, and higher odds of dementia were assessed in Black and White community-dwelling elders and racial differences in these associations were tested.

Methods: Black decedents (n=81) were matched two-to-one by age, sex, years of education and follow-up time in the study with White decedents (n=154), from four longitudinal studies of dementia and aging. Participants underwent uniform clinical examination, cognitive, motor and olfactory testing. LBs were detected in 7 brain regions by α-synuclein immunohistochemistry and racial differences in their association with olfaction, parkinsonism and odds of dementia were determined using regression analyses.

Results: The mean scores of the odor test, global parkinsonism signs, and global cognition were lower in Black than White decedents while the frequency of dementia was similar in both groups. The frequency of LBs was similar in Black and White decedents (∼ 25 %) as was the frequency of LBs in individual brain regions while the mean LB counts/mm were similar in all regions except the cingulate cortex which showed higher mean LB counts in Black decedents. In regression analyses, LBs were associated with impaired olfaction (-2.23, 95% CI -3.45 to -1.01) and higher odds of dementia (OR 3.0, 95% CI 1.10 to 8.17) in both racial groups while an association with parkinsonism was stronger in Black than White decedents.

Conclusions: The frequency, distribution, and clinical manifestations of LBs are similar in Black and White elders.
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http://dx.doi.org/10.1212/WNL.0000000000012324DOI Listing
June 2021

Immune-related gene expression signatures in colorectal cancer.

Oncol Lett 2021 Jul 20;22(1):543. Epub 2021 May 20.

R&D Department, Huaxia Bangfu Technology Incorporated, Beijing 100000, P.R. China.

The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with 'adaptive immune responses', 'innate immune responses' and 'cytokine signaling'. The survival analysis found that a high level of expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.
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http://dx.doi.org/10.3892/ol.2021.12804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157333PMC
July 2021

Objective Assessment of Daytime Napping and Incident Heart Failure in 1140 Community-Dwelling Older Adults: A Prospective, Observational Cohort Study.

J Am Heart Assoc 2021 Jun 2:e019037. Epub 2021 Jun 2.

Medical Biodynamics ProgramDivision of Sleep and Circadian DisordersBrigham and Women's Hospital Boston MA.

Background Disrupted nighttime sleep has been associated with heart failure (HF). However, the relationship between daytime napping, an important aspect of sleep behavior commonly seen in older adults, and HF remains unclear. We sought to investigate the association of objectively assessed daytime napping and risk of incident HF during follow-up. Methods and Results We studied 1140 older adults (age, 80.7±7.4 [SD] years; female sex, 867 [76.1%]) in the Rush Memory and Aging Project who had no HF at baseline and were followed annually for up to 14 years. Motor activity (ie, actigraphy) was recorded for ≈10 days at baseline. We assessed daytime napping episodes between 9 am and 7 pm objectively from actigraphy using a previously published algorithm for sleep detection. Cox proportional hazards models examined associations of daily napping duration and frequency with incident HF. Eighty-six participants developed incident HF, and the mean onset time was 5.7 years (SD, 3.4; range, 1-14). Participants who napped longer than 44.4 minutes (ie, the median daily napping duration) showed a 1.73-fold higher risk of developing incident HF than participants who napped <44.4 minutes. Consistently, participants who napped >1.7 times/day (ie, the median daily napping frequency) showed a 2.20-fold increase compared with participants who napped <1.7 times/day. These associations persisted after adjustment for covariates, including nighttime sleep, comorbidities, and cardiovascular disease/risk factors. Conclusions Longer and more frequent objective napping predicted elevated future risk of developing incident HF. Future studies are needed to establish underlying mechanisms.
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http://dx.doi.org/10.1161/JAHA.120.019037DOI Listing
June 2021

Single-Step Direct Laser Writing of Multimetal Oxygen Evolution Catalysts from Liquid Precursors.

ACS Nano 2021 Jun 1. Epub 2021 Jun 1.

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

We investigate a laser direct-write method to synthesize and deposit metastable, mixed transition metal oxides and evaluate their performance as oxygen evolution reaction catalysts. This laser processing method enabled the rapid synthesis of diverse heterogeneous alloy and oxide catalysts directly from cost-effective solution precursors, including catalysts with a high density of nanocrystalline metal alloy inclusions within an amorphous oxide matrix. The nanoscale heterogeneous structures of the synthesized catalysts were consistent with reactive force-field Monte Carlo calculations. By evaluating the impact of varying transition metal oxide composition ratios, we created a stable FeCoNiO/C catalyst with a Tafel slope of 38.23 mV dec and overpotential of 247 mV, a performance similar to that of IrO. Synthesized FeCoNiO/C and FeCoNiO/C catalysts were experimentally compared in terms of catalytic performance and structural characteristics to determine that higher iron content and a less crystalline structure in the secondary matrix decrease the charge transfer resistance and thus is beneficial for electrocatalytic activity. This conclusion is supported by density-functional theory calculations showing distorted active sites in ternary metal catalysts are key for lowering overpotentials for the oxygen evolution reaction.
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http://dx.doi.org/10.1021/acsnano.1c00650DOI Listing
June 2021

The "cognitive clock": A novel indicator of brain health.

Alzheimers Dement 2021 Jun 1. Epub 2021 Jun 1.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

Introduction: We identified a "cognitive clock," a novel indicator of brain health that provides person-specific estimates of cognitive age, and tested the hypothesis that cognitive age is a better predictor of brain health than chronological age in two independent datasets.

Methods: The initial analyses were based on 1057 participants from the Rush Memory and Aging Project and the Religious Orders Study who began without impairment and underwent cognitive assessments up to 24 years. A shape invariant model characterized the latent pattern of cognitive decline, conceptualized here as the "cognitive clock," and yielded person-specific estimates of cognitive age. Survival analyses examined cognitive versus chronological age for predicting Alzheimer's disease dementia, mild cognitive impairment and mortality, and regression analyses examined associations of cognitive versus chronological age with neuropathology and brain atrophy. Finally, we applied the cognitive clock to an independent validation sample of 2592 participants from the Chicago Health and Aging Project, a biracial population-based study, to confirm the predictive utility of cognitive age.

Results: The "cognitive clock" showed that cognition remained stable until a cognitive age of about 80, then declined moderately until 90, then declined precipitously. In the initial dataset, cognitive age was a better predictor of dementia, mild cognitive impairment and mortality than chronological age, and was more strongly associated with neuropathology and brain atrophy. Application of the cognitive clock to the independent validation sample provided further support for the utility of cognitive age as a strong prognostic indicator of adverse outcomes.

Discussion: Cognitive age is a robust prognostic indicator of adverse health outcomes and may serve as a useful biomarker in aging research.
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http://dx.doi.org/10.1002/alz.12351DOI Listing
June 2021

Lycopene Attenuates Hypoxia-Induced Testicular Injury by Inhibiting PROK2 Expression and Activating PI3K/AKT/mTOR Pathway in a Varicocele Adult Rat.

Evid Based Complement Alternat Med 2021 8;2021:3471356. Epub 2021 May 8.

Department of Urology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250014, Shandong, China.

Purpose: The aim of this study was to evaluate the effect of lycopene on hypoxia-induced testicular injury in rat model and explore the underlying mechanism.

Methods: Six-week-old male Wistar rats ( = 36) were randomly divided into three groups ( = 12/group): a normal group (NG, sham control), a varicocele group (VG), and a varicocele treated by lycopene group (VLG). Bilateral renal veins constriction was performed on rats in VG and VLG. Simultaneously, rats in VLG were treated to lycopene by intragastric administration. Four weeks later, sperm was collected for sperm analysis. Testes and epididymides were harvested for morphological change analysis, histologic analysis, ELISA, qRT-PCR, and western blot.

Results: Our observations were that lycopene improved the hypoxia-induced testicular injury in vivo. Prokineticin 2(PROK2) and prokineticin receptor 2 (PROKR2) were overexpressed in VG ( < 0.01), and lycopene inhibited the PROK2 expression ( < 0.01). Proliferating cell nuclear antigen (PCNA) and sex hormones were increased by lycopene in VLG ( < 0.05). Lycopene restored the quality and activity of sperm by blocking PROK2 expression ( < 0.05). The expression of VEGF was increased, as HIF-1/NF-B pathway was upregulated in VLG ( < 0.05). Meanwhile, expression of pAKT/AKT in VLG was higher than that in VG ( < 0.05). In addition, lycopene reduced levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) in VLG ( < 0.05), compared to NG.

Conclusions: Lycopene improved the hypoxia-induced testicular injury by inhibiting the expression of PROK2 and decreasing levels of IL-1 and IL-2, which might show us a novel and promising treatment for varicocele testicular injury.
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http://dx.doi.org/10.1155/2021/3471356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149244PMC
May 2021

Case Report: Amplified in a Thymoma Patient With Autoimmune Enteropathy and Myocarditis.

Front Endocrinol (Lausanne) 2021 13;12:661316. Epub 2021 May 13.

Department of Thoracic Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Introduction: Thymoma is a type of mediastinal malignant tumors which always associated with autoimmune diseases. Although surgery is the predominant treatment method for thymoma, the pathogenesis of thymoma and thymoma-associated autoimmune diseases is still unknown. However, the case study here provided a possible pathogenesis and treatment to cure the thymoma with autoimmune enteropathy and myocarditis.

Case Presentation: A thymoma case with autoimmune enteropathy and myocarditis undergoing surgery was reported. The symptoms and laboratory results of the patient had dramatically fluctuated after tumor resection and gradually alleviated. The whole exome sequencing found amplified in tumor cells. Immunohistochemistry indicated that thymoma cells were positive for MDM4. The result of drug sensitivity tests showed thymoma cells were highly sensitive to Nutlin-3a.

Conclusion: could play an important role in the pathogenesis of this thymoma case with autoimmune enteropathy and myocarditis. This discovery may provide a novel idea of pathogenesis and treatment for thymoma and autoimmune diseases.
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http://dx.doi.org/10.3389/fendo.2021.661316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155580PMC
May 2021

Bootstrap approach for meta-synthesis of MRI findings from multiple scanners.

J Neurosci Methods 2021 May 27;360:109229. Epub 2021 May 27.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, United States; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, United States; Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL 60612, United States.

Background: Neuroimaging data from large epidemiologic cohort studies often come from multiple scanners. The variations of MRI measurements due to differences in magnetic field strength, image acquisition protocols, and scanner vendors can influence the interpretation of aggregated data. The purpose of the present study was to compare methods that meta-analyze findings from a small number of different MRI scanners.

Methods: We proposed a bootstrap resampling method using individual participant data and compared it with two common random effects meta-analysis methods, DerSimonian-Laird and Hartung-Knapp, and a conventional pooling method that combines MRI data from different scanners. We first performed simulations to compare the power and coverage probabilities of the four methods in the absence and presence of scanner effects on measurements. We then examined the association of age with white matter hyperintensity (WMH) volumes from 787 participants.

Results: In simulations, the bootstrap approach performed better than the other three methods in terms of coverage probability and power when scanner differences were present. However, the bootstrap approach was consistent with pooling, the optimal approach, when scanner differences were absent. In the association of age with WMH volume, we observed that age was significantly associated with WMH volumes using the bootstrap approach, pooling, and the DerSimonian-Laird method, but not using the Hartung-Knapp method (p < 0.0001 for the bootstrap approach, DerSimonian-Laird, and pooling but p = 0.1439 for the Hartung-Knapp approach).

Conclusion: The bootstrap approach using individual participant data is suitable for integrating outcomes from multiple MRI scanners regardless of absence or presence of scanner effects on measurements.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109229DOI Listing
May 2021

Luteolin promotes macrophage-mediated phagocytosis by inhibiting CD47 pyroglutamation.

Transl Oncol 2021 May 26;14(8):101129. Epub 2021 May 26.

Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:

'Don't eat me' signal of CD47 is activated via its interaction with SIRPα protein on myeloid cells, especially phagocytic cells, and prevents malignant cells from anti-tumor immunity in which pyroglutamate modification of CD47 by glutaminyl-peptide cyclotransferase-like protein (isoQC) takes an important part evidenced by our previous report that isoQC is an essential regulator for CD47-SIRPα axis with a strong inhibition on macrophage-mediated phagoctyosis. Therefore, we screened for potential isoQC inhibitors by fluorescence-activated cell sorting assay and identified luteolin as a potent compound that blocked the pyroglutamation of CD47 by isoQC. We further demonstrated that luteolin directly bound to isoQC using pull-down assay and isothermal calorimetric (ITC) assay. In consistency, we showed that luteolin markedly abrogated the cell-surface interaction between CD47 and SIRPα in multiple myeloma H929 cells and consequently promoted the macrophage-mediated phagocytosis. Collectively, our study discovered a promising lead compound targeting isoQC, luteolin, which functions distinctly from current CD47 antibody-based drugs and therefore may potentially overcome the clinical side effects associated with CD47 antibody treatment-induced anemia.
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http://dx.doi.org/10.1016/j.tranon.2021.101129DOI Listing
May 2021

Cortical proteins may provide motor resilience in older adults.

Sci Rep 2021 May 28;11(1):11311. Epub 2021 May 28.

Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 West Harrison Street, Jelke Building, Suite 100, Chicago, IL, 60612, USA.

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.
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http://dx.doi.org/10.1038/s41598-021-90859-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163829PMC
May 2021

Risk Score for Predicting Dysphagia in Patients After Neurosurgery: A Prospective Observational Trial.

Front Neurol 2021 11;12:605687. Epub 2021 May 11.

Department of Nursing, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Acquired dysphagia is common in patients with tracheal intubation and neurological disease, leading to increased mortality. This study aimed to ascertain the risk factors and develop a prediction model for acquired dysphagia in patients after neurosurgery. A multicenter prospective observational study was performed on 293 patients who underwent neurosurgery. A standardized swallowing assessment was performed bedside within 24 h of extubation, and logistic regression analysis with a best subset selection strategy was performed to select predictors. A nomogram model was then established and verified. The incidence of acquired dysphagia in our study was 23.2% (68/293). Among the variables, days of neurointensive care unit (NICU) stay [odds ratio (OR), 1.433; 95% confidence interval (CI), 1.141-1.882; = 0.005], tracheal intubation duration (OR, 1.021; CI, 1.001-1.062; = 0.175), use of a nasogastric feeding tube (OR, 9.131; CI, 1.364-62.289; = 0.021), and Acute Physiology and Chronic Health Evaluation (APACHE)-II C score (OR, 1.709; CI, 1.421-2.148; < 0.001) were selected as risk predictors for dysphagia and included in the nomogram model. The area under the receiver operating characteristic curve was 0.980 (CI, 0.965-0.996) in the training set and 0.971 (0.937-1) in the validation set, with Brier scores of 0.045 and 0.056, respectively. Patients who stay longer in the NICU, have a longer duration of tracheal intubation, require a nasogastric feeding tube, and have higher APACHE-II C scores after neurosurgery are likely to develop dysphagia. This developed model is a convenient and efficient tool for predicting the development of dysphagia.
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http://dx.doi.org/10.3389/fneur.2021.605687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144441PMC
May 2021

Learning spatiotemporal features of DSA using 3D CNN and BiConvGRU for moyamoya disease detection.

Int J Neurosci 2021 May 27:1-14. Epub 2021 May 27.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Moyamoya disease (MMD) is a serious intracranial cerebrovascular disease. Cerebral hemorrhage caused by MMD will bring life risk to patients. Therefore, MMD detection is of great significance in the prevention of cerebral hemorrhage. In order to improve the accuracy of digital subtraction angiography (DSA) in the diagnosis of MMD, in this paper, a deep network architecture combined with 3 D convolutional neural network (3 D CNN) and bidirectional convolutional gated recurrent unit (BiConvGRU) is proposed to learn the spatiotemporal features for MMD detection. Firstly, 2 D convolutional neural network (2 D CNN) is utilized to extract spatial features for each frame of DSA. Secondly, the long-term spatiotemporal features of DSA sequence are extracted by BiConvGRU. Thirdly, the short-term spatiotemporal features of DSA are further extracted by 3 D convolutional neural network (3 D CNN). In addition, different features are extracted when gray images and optical flow images pass through the network, and multiple features are extracted by features fusion. Finally, the fused features are utilized to classify. The proposed method was quantitatively evaluated on a data sets of 630 cases. The experimental results showed a detection accuracy of 0.9788, sensitivity and specificity were 0.9780 and 0.9796, respectively, and area under curve (AUC) was 0.9856. Compared with other methods, we can get the highest accuracy and AUC. The experimental results show that the proposed method is stable and reliable for MMD detection, which provides an option for doctors to accurately diagnose MMD.
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http://dx.doi.org/10.1080/00207454.2021.1929214DOI Listing
May 2021

Clinical Efficiency of Non-invasive Prenatal Screening for Common Trisomies in Low-Risk and Twin Pregnancies.

Front Genet 2021 10;12:661884. Epub 2021 May 10.

Department of Reproductive Genetics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

To evaluate the clinical efficiency of non-invasive prenatal screening (NIPS) for fetal aneuploidies in low-risk and twin pregnancies, patients who received NIPS in a tertiary university hospital were enrolled, and their clinical data, NIPS results and pregnancy outcomes were collected. Patients were divided into singleton and twin pregnancies, and then those with singleton pregnancies were divided into low- and high-risk pregnancies. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Comparisons were made on the clinical efficiency of NIPS between singleton and twin pregnancies, as well as between low- and high-risk pregnancies. Of 66,172 patients enrolled, 59,962 were eligible for analysis. The sensitivity, specificity and NPV were ≥ 99% in singleton and twin pregnancies. The PPVs were 90.4, 56.6, and 13.0% in singleton pregnancies, while 100, 33.3, and 0% in twin pregnancies for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), respectively ( > 0.05 for all). The PPVs were 97.4 and 90.0% in high-risk pregnancies, while 78.6 and 16.7% in low-risk pregnancies for T21 and T18, respectively ( < 0.05 for all). In summary, the performance of NIPS in singleton pregnancies was similar to that in twin pregnancies. NIPS can be recommended for all pregnancies regardless of the risks.
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http://dx.doi.org/10.3389/fgene.2021.661884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143437PMC
May 2021

Corrigendum to "Removal and tolerance mechanism of Pb by a filamentous fungus: A case study" [Chemosphere 225 (2019) 200-208].

Chemosphere 2021 May 24:130938. Epub 2021 May 24.

College of Forestry, Henan Agricultural University, Zhengzhou, 450002, China. Electronic address:

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http://dx.doi.org/10.1016/j.chemosphere.2021.130938DOI Listing
May 2021

CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

J Hematol Oncol 2021 May 25;14(1):82. Epub 2021 May 25.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92-99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117-261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.
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http://dx.doi.org/10.1186/s13045-021-01092-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152118PMC
May 2021

Impact of Early Life Socioeconomic Status on Decision Making in Older Adults Without Dementia.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104432. Epub 2021 May 9.

Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 West Harrison St. Suite 1000, Chicago, IL 60612; Department of Psychiatry and Behavioral Sciences.

Objectives: A growing body of evidence points to the negative impact of early life socioeconomic status (SES) on health and cognitive outcomes in later life. However, the effect of early life SES on decision making in old age is not well understood. This study investigated the association of early life SES with decision making in a large community-based cohort of older adults without dementia from the Rush Memory and Aging Project.

Materials And Methods: Cross-sectional data from the Rush Alzheimer's Disease Center Memory and Aging Project was analyzed. Participants were 1044 community-dwelling older adults without dementia (M age = 81.15, SD = 7.49; 75.8% female; 5.4% non-White). Measures of financial and healthcare decision making and early life SES were collected, along with demographics, global cognition, and financial and health literacy.

Results: Early life SES was positively associated with decision making (estimate = 0.218, p = 0.027), after adjustments for demographic covariates and global cognition, such that a one-unit increase in early life SES was equivalent to the effect of being four years younger in age as it pertains to decision making. A subsequent model demonstrated that the relationship was strongest in those with low literacy, and weakest for those with high literacy (estimate = -0.013, p = 0.029).

Conclusions: Findings from this study suggest that early life SES is associated with late life decision making and that improving literacy, a modifiable target for intervention, may buffer the negative impact of low early life SES on decision making in older adulthood.
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http://dx.doi.org/10.1016/j.archger.2021.104432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175072PMC
May 2021

Tolerance niche expansion and potential distribution prediction during Asian openbill bird range expansion.

Authors:
Yu Lei Qiang Liu

Ecol Evol 2021 May 24;11(10):5562-5574. Epub 2021 Mar 24.

College of Wetlands Southwest Forestry University Kunming China.

It is prevalent to use ecological niche models in the analysis of species expansion and niche changes. However, it is difficult to estimate the niche when alien species fail to establish in exotic areas. Here, we applied the tolerance niche concept, which means that niche of species can live and grow but preclude a species from establishing self-sustaining populations, in such fail-to-establish events. Taking the rapidly expanded bird, Asian openbill (), as a model species, we investigated niche dynamics and its potential effects on the population by Niche A and ecospat, predicted potential distribution by biomod2. Results showed that niche expansion has occurred in two non-native populations caused by the tolerance of colder and wetter environments, and potential distribution mainly concentrated on equatorial islands. Our study suggested that the expanded niche belongs to tolerance niche concept according to the populations' dynamics and GPS tracking evidence. It is essential to consider source populations when we analyze the alien species. We recommended more consideration to the application of tolerance niche in alien species research, and there is still a need for standard measurement frameworks for analyzing the tolerance niche.
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http://dx.doi.org/10.1002/ece3.7456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131807PMC
May 2021

Boosting predictabilities of agronomic traits in rice using bivariate genomic selection.

Brief Bioinform 2021 May;22(3)

University of California, Riverside, USA.

The multivariate genomic selection (GS) models have not been adequately studied and their potential remains unclear. In this study, we developed a highly efficient bivariate (2D) GS method and demonstrated its significant advantages over the univariate (1D) rival methods using a rice dataset, where four traditional traits (i.e. yield, 1000-grain weight, grain number and tiller number) as well as 1000 metabolomic traits were analyzed. The novelty of the method is the incorporation of the HAT methodology in the 2D BLUP GS model such that the computational efficiency has been dramatically increased by avoiding the conventional cross-validation. The results indicated that (1) the 2D BLUP-HAT GS analysis generally produces higher predictabilities for two traits than those achieved by the analysis of individual traits using 1D GS model, and (2) selected metabolites may be utilized as ancillary traits in the new 2D BLUP-HAT GS method to further boost the predictability of traditional traits, especially for agronomically important traits with low 1D predictabilities.
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http://dx.doi.org/10.1093/bib/bbaa103DOI Listing
May 2021

Chaperonin-Containing TCP1 Subunit 6A Is a Prognostic Potential Biomarker That Correlates With the Presence of Immune Infiltrates in Colorectal Cancer.

Front Genet 2021 4;12:629856. Epub 2021 May 4.

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Aims: Chaperonin-containing TCP1 subunit (CCT) 6A is an oncogenic 6th subunit of the CCT family. Nevertheless, not much is documented regarding its function in colorectal cancer (COAD). This investigation seeks to explore the role of in the prognosis of COAD.

Main Methods: Sequencing data from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas database (TCGA) were employed to analyze the expression of and its involvement in various regulatory networks behind COAD. Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) analyzed Levels of expression and survival rates, while GEPIA was used to uncover further the functional networks that involved . Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools were used to interpret Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Evaluation of the expression levels of in COAD samples was also verified via immunohistochemistry.

Key Findings: We found that the expression of is up-regulated in COAD. correlated with poor prognosis and decreased immune infiltrates such as CD4 T cells, B cells, and dendritic cells. is increased in COAD patients. is associated with several gene networks related to the DDX family and mismatch repair pathways.

Significance: Our data showed that data mining was able to uncover data regarding levels of and its involvement in genetic regulating pathways in COAD.
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http://dx.doi.org/10.3389/fgene.2021.629856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129517PMC
May 2021

UV irradiation of N-chloro-α-amino acids: Kinetics, mechanisms, and N-DBP formation potentials.

Water Res 2021 Jul 6;199:117204. Epub 2021 May 6.

School of Environmental Science and Engineering, Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, Sun Yat-sen University, Guangzhou, 510275, China.

This study explores the degradation kinetics and mechanisms of N-chloro-α-amino acids and the changes in the formation potential of nitrogenous disinfection byproducts (N-DBPs) upon UV irradiation. UV irradiation significantly accelerated the degradation of all the tested N-chloro-α-amino acids compared to those in the dark. Both direct photolysis-induced cleavage of the N-Cl bonds and radical oxidation (e.g., Cl and Cl) involved reactions that contributed to their enhanced degradation. The fluence-based photolysis rate constants of the N-chloro-α-amino acids varied in the range of (1.06-5.47) × 10 cm mJ at pH 6.0 and (0.74-2.79) × 10 cm mJ at pH 8.0. The apparent quantum yields (Φ) of the majority of the N-chloro-α-amino acids were in the range of 0.41-0.95 at pH 6.0 and 0.22-0.79 at pH 8.0, except N-chloroaspartic acid, N-chlorohistidine, and N-chloroalanine. UV irradiation significantly enhanced the formation of trichloronitromethane (TCNM) from the tested N-chloro-α-amino acids after post-chlorination, but exhibited various effects on the formation of dichloroacetonitrile (DCAN). A longer UV irradiation time generated more TCNM, and a lower pH produced more DCAN from the N-chloro-α-amino acids. The degradation pathways of N-chlorotyrosine, as a representative N-chloro-α-amino acid, are proposed, and the β-scission and 1,2-H shift pathways led to the formation of different precursors of TCNM and DCAN. The results of this study improve our understanding of the fate of N-chloro-α-amino acids under UV irradiation and post-chlorination.
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http://dx.doi.org/10.1016/j.watres.2021.117204DOI Listing
July 2021

Sorption of micropollutants on selected constructed wetland support matrices.

Chemosphere 2021 Jul 23;275:130050. Epub 2021 Feb 23.

Environmental Technology, Wageningen University & Research, 6700, AA, Wageningen, the Netherlands.

Micropollutants (MPs) are organic chemicals that are present in the environment at low concentrations (ng/L-μg/L), for example pharmaceuticals. A constructed wetland (CW) is a promising post-treatment technique to remove MPs from wastewater effluent. Selecting a suitable material for support matrix is important when designing such a CW. Nine materials were studied as potential support matrices: Light Expanded Clay Aggregates (LECA), compost, bark, granulated activated carbon (GAC), biochar, granulated cork, lava rock, sand and gravel. Batch experiments were conducted to study MP removal by nine materials in phosphate buffer with 5 or 50 μg/L MPs, or wastewater effluent with 50 μg/L of MPs. GAC and biochar removed almost all MPs in both phosphate buffer and wastewater effluent, followed by bark, compost, granulated cork. Sand, gravel, LECA and lava rock removed less than 30% of most MPs in both matrixes. Based on set criteria (e.g. removal efficiency), biochar, bark, compost, LECA and sand were selected, and used in combinations in column studies to test their overall performance. A combination of bark and biochar performed the best on MP removal, as 4 MPs were highly (70%-100%) removed, 4 MPs were moderately (30%-70%) removed while only 3 MPs were hardly removed. The main flow regime of this combination was both plug flow and dispersive flow. Moreover, we hypothesized to apply bark and biochar in a CW. Based on the assumptions and calculations, some benefits are expected, such as increasing MP removal and extending operation time.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130050DOI Listing
July 2021

Depletion of MRPL35 inhibits gastric carcinoma cell proliferation by regulating downstream signaling proteins.

World J Gastroenterol 2021 Apr;27(16):1785-1804

Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China.

Background: Gastric carcinoma (GC) is a digestive system disease with high morbidity and mortality. However, early clinical detection is difficult, and the therapeutic effect for advanced disease is not satisfactory. Thus, finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative. MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein. MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer, which promotes the exploration of the correlation between MRPL35 and GC. We proposed that the expression of MRPL35 might be critical in GC.

Aim: To study the effect of knockdown on GC cell proliferation.

Methods: The expression of in GC was evaluated based on data from the public tumor database UALCAN (www.ualcan.path.uab.edu). The effect of the expression of on the prognosis was evaluated with KMplot (www.kmplot.com). The expression of MRPL35 was assessed on the tissue microarray by immunohistochemistry and the level of mRNA in 25 pairs of clinical GC tissues and matched adjacent tissues was detected by quantitative reverse transcription-polymerase chain reaction. Celigo cell count assay, colony formation assay, and flow cytometry were used to assess the role of MRPL35 in GC cell proliferation and apoptosis . Additionally, tumor formation experiment in BALB/c nude mice was utilized to determine the effect of on GC cell proliferation. After knockdown of , related proteins were identified by isobaric tags for relative and absolute quantification analysis, and the expression of related proteins was detected by Western blot.

Results: The expression of MRPL35 was up-regulated in GC ( = 1.77 × 10). The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 was associated with a poor survival in GC. Compared with adjacent tissues, the expression of MRPL35 in GC tissues was increased, which was related to age ( = 0.03), lymph node metastasis ( = 0.007), and pathological tumor-node-metastasis stage ( = 0.024). Knockdown of inhibited GC cell proliferation and colony formation and induced apoptosis. Animal experiment results showed that knockdown of inhibited tumor formation in BALB/c nude mice. Western blotting analysis showed that after knockdown of , the expression of PICK1 and BCL-XL proteins decreased, and that of AGR2 protein increased.

Conclusion: Collectively, our findings demonstrate that knockdown of inhibits GC cell proliferation through related proteins including PICK1, BCL-XL, and AGR2.
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http://dx.doi.org/10.3748/wjg.v27.i16.1785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072187PMC
April 2021

AQP2 as a target of lycopene protects against atrazine-induced renal ionic homeostasis disturbance.

Food Funct 2021 Jun;12(11):4855-4863

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China. and Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, P. R. China and Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China.

Atrazine (ATR), a ubiquitous environmental contaminant in water and soil, causes environmental nephrosis. To reveal the toxic effect of ATR on the kidney and the potential chemical nephroprotective effect of lycopene (LYC), Kun-Ming mice of specific pathogen-free (SPF) grade were treated with LYC (5 mg kg-1) and/or ATR (50 mg kg-1 or 200 mg kg-1) for 21 days. The degree of renal injury was evaluated by measuring the ion concentration, ATPase activities and the mRNA expressions/levels of associated ATPase subunits. In addition, the expression of renal aquaporins (AQPs) was analyzed. The results showed that the renal tubular epithelial cells of ATR-exposed mice were swollen, the glomeruli were significantly atrophied, and the ion concentrations were obviously changed. The activity of Na+-K+-ATPase and the transcription of its subunits were downregulated. The activity of Ca2+-Mg2+-ATPase and the transcription of its subunits were upregulated. The expression of AQPs, especially the critical AQP2, was affected. Notably, ATR-induced nephrotoxicity was significantly improved by LYC supplementation. Therefore, LYC could protect the kidney against ATR-induced nephrotoxicity via maintaining ionic homeostasis, reversing the changes in ATPase activity and controlling the expression of AQPs on the cell membrane. These results suggested that AQP2 was a target of LYC and protected against ATR-induced renal ionic homeostasis disturbance.
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http://dx.doi.org/10.1039/d0fo03214jDOI Listing
June 2021