Publications by authors named "Zhongping Chen"

348 Publications

OCT Evaluation of Vaginal Epithelial Thickness during CO Laser Treatment: A Pilot Study.

J Biophotonics 2022 Jul 20:e202200052. Epub 2022 Jul 20.

Beckman Laser Institute & Medical Clinic, University of California, Irvine, Irvine, CA, USA.

Genitourinary syndrome of menopause (GSM) negatively affects more than half of postmenopausal women. Energy-based therapy has been explored as a minimally invasive treatment for GSM; however, its mechanism of action and efficacy is controversial. Here, we report on a pilot imaging study conducted on a small group of menopause patients undergoing laser treatment. Intravaginal optical coherence tomography (OCT) endoscope was used to quantitatively monitor the changes in the vaginal epithelial thickness (VET) during fractional-pixel CO laser treatment. 11 patients with natural menopause and 1 surgically induced menopause patient were recruited in this clinical study. Following the laser treatment, the 6 out of 11 natural menopause patient showed increase in both proximal and distal VET, while 2 natural menopause patient showed increase in VET in only one side of vaginal tract. Furthermore, the patient group that showed increased VET had thinner baseline VET compared to the patients that showed decrease in VET after laser treatment. These results demonstrate the potential utility of intravaginal OCT endoscope in evaluating the vaginal tissue integrity and tailoring vaginal laser treatment on a per-person basis, with the potential to monitor other treatment procedures. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jbio.202200052DOI Listing
July 2022

Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against -null glioblastoma.

Sci Adv 2022 07 8;8(27):eabl5165. Epub 2022 Jul 8.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China.

Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, -deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3β-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for -null GBM.
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http://dx.doi.org/10.1126/sciadv.abl5165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269888PMC
July 2022

Establishment of a human induced pluripotent stem cell line (CSUASOi010-A) by reprogramming peripheral blood mononuclear cells of a type 2 diabetic mellitus patient.

Stem Cell Res 2022 Aug 7;63:102851. Epub 2022 Jul 7.

Aier Eye Institute, 18th Floor, the New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Aier School of Ophthalmology, Central South University, P.R.C., 18th Floor, the New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China; Institute of Ophthalmology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address:

Type 2 diabetes mellitus (T2DM) is a major caused by insulin resistance with a relative deficiency in insulin secretion. Statistically, T2DM accounts for 90% of diabetes cases worldwide. We report the patient-specific human induced pluripotent stem cell line (iPSC) CSUASOi010-A by using Peripheral blood mononuclear cells (PBMCs) of a 62-year-old female from Type 2 diabetes mellitus (T2DM). Patient blood-derived cells were reprogrammed using the Sendai virus.
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http://dx.doi.org/10.1016/j.scr.2022.102851DOI Listing
August 2022

Establishment of a human induced pluripotent stem cell line (CSUASOi010-A) by reprogramming peripheral blood mononuclear cells of a type 2 diabetic mellitus patient.

Stem Cell Res 2022 Aug 7;63:102851. Epub 2022 Jul 7.

Aier Eye Institute, 18th Floor, the New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Aier School of Ophthalmology, Central South University, P.R.C., 18th Floor, the New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China; Institute of Ophthalmology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address:

Type 2 diabetes mellitus (T2DM) is a major caused by insulin resistance with a relative deficiency in insulin secretion. Statistically, T2DM accounts for 90% of diabetes cases worldwide. We report the patient-specific human induced pluripotent stem cell line (iPSC) CSUASOi010-A by using Peripheral blood mononuclear cells (PBMCs) of a 62-year-old female from Type 2 diabetes mellitus (T2DM). Patient blood-derived cells were reprogrammed using the Sendai virus.
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http://dx.doi.org/10.1016/j.scr.2022.102851DOI Listing
August 2022

Suppression of EZH2 inhibits TGF-β1-induced EMT in human retinal pigment epithelial cells.

Exp Eye Res 2022 Jun 30;222:109158. Epub 2022 Jun 30.

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China; Aier Eye Institute, Changsha, Hunan Province, China; Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China. Electronic address:

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is critically involved in the occurrence of subretinal fibrosis. This study aimed to investigate the role of enhancer of zeste homolog 2 (EZH2) in EMT of human primary RPE cells and the underlying mechanisms of the anti-fibrotic effect of EZH2 suppression. Primary cultures of human RPE cells were treated with TGF-β1 for EMT induction. EZH2 was silenced by siRNA to assess the expression levels of epithelial and fibrotic markers using qRT-PCR, Western blot, and immunofluorescence staining assay. Furthermore, the cellular migration, proliferation and barrier function of RPE cells were evaluated. RNA-sequencing analyses were performed to investigate the underlying mechanisms of EZH2 inhibition. Herein, EZH2 silencing up-regulated epithelial marker ZO-1 and downregulated fibrotic ones including α-SMA, fibronectin, and collagen 1, alleviating EMT induced by TGF-β1 in RPE cells. Moreover, silencing EZH2 inhibited cellular migration and proliferation, but didn't affect cell apoptosis. Additionally, EZH2 suppression contributed to improved barrier functions after TGF-β1 stimulation. The results from RNA sequencing suggested that the anti-fibrotic effect of EZH2 inhibition was associated with the MAPK signaling pathway, cytokine-cytokine receptor interaction, and the TGF-beta signaling pathway. Our findings provide evidence that the suppression of EZH2 might reverse EMT and maintain the functions of RPE cells. EZH2 could be a potential therapeutic avenue for subretinal fibrosis.
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http://dx.doi.org/10.1016/j.exer.2022.109158DOI Listing
June 2022

Visualization of ex vivo rabbit olfactory mucosa and foramina with three-dimensional optical coherence tomography.

Lasers Med Sci 2022 Jul 2. Epub 2022 Jul 2.

Beckman Laser Institute & Medical Clinic, University of California - Irvine, Irvine, CA, USA.

There is increasing interest in developing a minimally invasive imaging modality to safely evaluate dynamic microscopic changes of the olfactory mucosa and cribriform foramina. Herein, we utilized three-dimensional (3D) optical coherence tomography (OCT) to characterize the ex vivo stratified substructure of olfactory mucosa in rabbits and create 3D reconstructed images of olfactory foramina. Olfactory mucosa and cribriform plates from four New Zealand White rabbits were dissected and imaged using two swept-source OCT systems: (1) 1.3-µm (μm) center wavelength, 100-nm bandwidth, 200-kHz sweep rate, and (2) 1.7-μm center wavelength, 120-nm bandwidth, 90-kHz sweep rate. Volumetric OCT images were compiled to create a 3D reconstruction of the cribriform plate. The ability of OCT to distinguish the olfactory mucosa substructure and foramina was compared to histology. To estimate imaging penetration depth of each system, the first-order exponential decays of depth-resolved intensity were calculated and compared using a paired t-test. Three-dimensional OCT depicted the stratified layered structures within the olfactory mucosa correlating with histology. The epithelium and lamina propria were measured to be 32 μm and 107 μm in 1.3-μm OCT compared to 30 μm and 105 μm in histology. Olfactory foramina were visualized via 3D reconstruction. The 1.7-μm system provided greater depth penetration compared to the 1.3-μm system, allowing for improved foramina visualization. We have shown that OCT can be used to image non-pathologic olfactory mucosa and foramina. Implications for this work include diagnostic and therapeutic potentials for neurorhinological and neurodegenerative diseases.
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http://dx.doi.org/10.1007/s10103-022-03598-wDOI Listing
July 2022

Analyses of n-back high-load working memory in early Parkinson's disease: An fMRI study.

J Clin Neurosci 2022 Aug 20;102:80-86. Epub 2022 Jun 20.

Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:

Background: Cognitive impairment is common in Parkinson's disease (PD). Working memory is a group of basic processes that is part of many cognitive operations (from complex decision-making to selective attention). To date, there is not sufficient research on working memory impairment in early PD patients, especially patients under high load.

Aim: The aim of this study was to observe the activation of brain regions in early PD patients during verbal high-load cognitive tasks and to explore the correlation between cognitive behavior indexes and gray matter areas of brain structure.

Methods: A total of 45 participants were included: 15 healthy controls and 30 PD patients without dementia. They underwent BOLD imaging during a digital N-back working memory task in a 3 T scanner, and their high-resolution T1-weighted three-dimensional brain anatomical images were collected. The SPM12 standard method was used to generate a comparison map with 2 plus 3-back greater than 0-back, and with age, sex, levodopa equivalent daily dose (LEDD) and education as covariables, and multiple regression analysis was conducted to analyze the correlation between MOCA, MES and brain gray matter volume.

Results: Compared with the control group, the frontoparietal region was significantly activated in patients with PD under the background of high working memory burden. In addition, there was a widespread area correlation between the brain structure and basic cognitive function.

Conclusions: The frontoparietal cortex is the core hub of working memory, and there may be a compensation mechanism in PD patients without dementia with a high-load of working memory.
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http://dx.doi.org/10.1016/j.jocn.2022.06.010DOI Listing
August 2022

Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells.

Cell Death Dis 2022 May 24;13(5):493. Epub 2022 May 24.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Accumulating evidence supports the existence of glioma stem cells (GSCs) and their critical role in the resistance to conventional treatments for glioblastoma multiforme (GBM). Differentiation therapy represents a promising alternative strategy against GBM by forcing GSCs to exit the cell cycle and reach terminal differentiation. In this study, we demonstrated that cAMP triggered neuronal differentiation and compromised the self-renewal capacity in GSCs. In addition, cAMP induced negative feedback to antagonize the differentiation process by activating β-catenin pathway. Suppression of β-catenin signaling synergized with cAMP activators to eliminate GSCs in vitro and extended the survival of animals in vivo. The cAMP/PKA pathway stabilized β-catenin through direct phosphorylation of the molecule and inhibition of GSK-3β. The activated β-catenin translocated into the nucleus and promoted the transcription of APELA and CARD16, which were found to be responsible for the repression of cAMP-induced differentiation in GSCs. Overall, our findings identified a negative feedback mechanism for cAMP-induced differentiation in GSCs and provided potential targets for the reinforcement of differentiation therapy for GBM.
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http://dx.doi.org/10.1038/s41419-022-04957-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130142PMC
May 2022

Effects of Organic Chromium Yeast on Performance, Meat Quality, and Serum Parameters of Grow-Finish Pigs.

Biol Trace Elem Res 2022 May 6. Epub 2022 May 6.

Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

Trivalent chromium (Cr) is an essential trace element for humans and animals. This study was conducted to investigate the effects of chromium(III) yeast (CrYst) on growth performance, carcass characteristics, meat traits, antioxidant status, immune traits, and serum biochemical parameters of grow-finish pigs. A total of 72 commercial hybrid barrows (Duroc × Landrace × Large White) of approximately 50 kg body weight were allocated into two dietary treatments randomly, which received a corn-soybean meal basal diet or a basal diet supplemented with 100 mg CrYst/kg. The trial duration was 11 weeks divided into three periods from body weights of 50-75 kg, 75-100 kg, and 100-110 kg, respectively. The results revealed that supplemental CrYst did not affect growth performance. Organic CrYst supplementation significantly decreased the backfat depth and increased the meat tenderness score and juiciness score values in pigs (P < 0.05), while other carcass traits and meat traits indexes were unaffected. CrYst addition significantly decreased serum malondialdehyde (MDA) content of pigs in the whole growth phase; significantly increased the serum levels of immunoglobulin G (IgG), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) in growing pigs; and also increased the serum IgG, IgM, and GSH concentrations in pigs during the finishing phase (P < 0.05). Additionally, diets supplemented with CrYst significantly decreased the serum high-density lipoprotein cholesterol (HDL-C) content in growing pigs and significantly increased the serum LDL-C level at the fattening period (P < 0.05), whereas no significant differences were observed for the other serum biochemical indexes compared to the control pigs. In conclusion, CrYst supplementation could reduce lipid peroxidation and backfat thickness and improve the meat tenderness and juiciness, immune traits, and antioxidant status of pigs.
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http://dx.doi.org/10.1007/s12011-022-03237-zDOI Listing
May 2022

Intravascular polarization-sensitive optical coherence tomography based on polarization mode delay.

Sci Rep 2022 04 27;12(1):6831. Epub 2022 Apr 27.

Beckman Laser Institute, University of California, Irvine, Irvine, CA, 92617, USA.

Intravascular polarization-sensitive optical coherence tomography (IV-PSOCT) provides depth-resolved tissue birefringence which can be used to evaluate the mechanical stability of a plaque. In our previous study, we reported a new strategy to construct polarization-sensitive optical coherence tomography in a microscope platform. Here, we demonstrated that this technology can be implemented in an endoscope platform, which has many clinical applications. A conventional intravascular OCT system can be modified for IV-PSOCT by introducing a 12-m polarization-maintaining fiber-based imaging probe. Its two polarization modes separately produce OCT images of polarization detection channels spatially distinguished by an image separation of 2.7 mm. We experimentally validated our IV-PSOCT with chicken tendon, chicken breast, and coronary artery as the image samples. We found that the birefringent properties can be successfully visualized by our IV-PSOCT.
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http://dx.doi.org/10.1038/s41598-022-10709-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046432PMC
April 2022

Hypoxia-Responsive Stereocomplex Polymeric Micelles with Improved Drug Loading Inhibit Breast Cancer Metastasis in an Orthotopic Murine Model.

ACS Appl Mater Interfaces 2022 May 27;14(18):20551-20565. Epub 2022 Apr 27.

Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226019, People's Republic of China.

Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis.
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http://dx.doi.org/10.1021/acsami.1c23737DOI Listing
May 2022

Enhance the delivery of light energy ultra-deep into turbid medium by controlling multiple scattering photons to travel in open channels.

Light Sci Appl 2022 Apr 24;11(1):108. Epub 2022 Apr 24.

Beckman Laser Institute, University of California, Irvine, Irvine, CA, 92612, USA.

Multiple light scattering is considered as the major limitation for deep imaging and focusing in turbid media. In this paper, we present an innovative method to overcome this limitation and enhance the delivery of light energy ultra-deep into turbid media with significant improvement in focusing. Our method is based on a wide-field reflection matrix optical coherence tomography (RM-OCT). The time-reversal decomposition of the RM is calibrated with the Tikhonov regularization parameter in order to get more accurate reversal results deep inside the scattering sample. We propose a concept named model energy matrix, which provides a direct mapping of light energy distribution inside the scattering sample. To the best of our knowledge, it is the first time that a method to measure and quantify the distribution of beam intensity inside a scattering sample is demonstrated. By employing the inversion of RM to find the matched wavefront and shaping with a phase-only spatial light modulator, we succeeded in both focusing a beam deep (~9.6 times of scattering mean free path, SMFP) inside the sample and increasing the delivery of light energy by an order of magnitude at an ultra-deep (~14.4 SMFP) position. This technique provides a powerful tool to understand the propagation of photon in a scattering medium and opens a new way to focus light inside biological tissues.
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http://dx.doi.org/10.1038/s41377-022-00795-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035453PMC
April 2022

A New Pyrroloquinoline-Derivative-Based Fluorescent Probe for the Selective Detection and Cell Imaging of Lysine.

Pharmaceuticals (Basel) 2022 Apr 13;15(4). Epub 2022 Apr 13.

School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China.

In this paper, a new pyrroloquinoline-derivative-based fluorescent probe, , was prepared for the selective detection of Lys in living cells and natural mineral water for drinking. exhibited high selectivity, low limit of detection, and a wide pH range. could be successfully applied for imaging Lys in living cells and in natural mineral water for drinking. We expect that will expand the detection reaction mechanism and the practical biological applications of Lys.
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http://dx.doi.org/10.3390/ph15040474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029482PMC
April 2022

Advances in Endoscopic Photoacoustic Imaging.

Photonics 2021 Jul 16;8(7). Epub 2021 Jul 16.

Beckman Laser Institute, University of California Irvine, Irvine, CA 92617, USA.

Photoacoustic (PA) imaging is able to provide extremely high molecular contrast while maintaining the superior imaging depth of ultrasound (US) imaging. Conventional microscopic PA imaging has limited access to deeper tissue due to strong light scattering and attenuation. Endoscopic PA technology enables direct delivery of excitation light into the interior of a hollow organ or cavity of the body for functional and molecular PA imaging of target tissue. Various endoscopic PA probes have been developed for different applications, including the intravascular imaging of lipids in atherosclerotic plaque and endoscopic imaging of colon cancer. In this paper, the authors review representative probe configurations and corresponding preclinical applications. In addition, the potential challenges and future directions of endoscopic PA imaging are discussed.
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http://dx.doi.org/10.3390/photonics8070281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896876PMC
July 2021

16S rDNA sequencing analyzes differences in intestinal flora of human immunodeficiency virus (HIV) patients and association with immune activation.

Bioengineered 2022 02;13(2):4085-4099

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

To clarify the influence of HIV on the intestinal flora and the interrelationship with CD4 T cells, the present study collected stool specimens from 33 HIV patients and 28 healthy subjects to compare the differences in the intestinal flora and CD4 T cells in a 16S rDNA-sequencing approach. ELISA was used to detect the expressions of interleukin 2 (IL-2), IL-8, and tumor necrosis factor-α (TNF-α). Meanwhile, correlation analysis with the different bacterial populations in each group was carried out. The results revealed that Alpha diversity indices of the intestinal flora of HIV patients were markedly lower than that of the healthy group (p < 0.05). The top five bacterial species in the HIV group were Bacteroides (23.453%), Prevotella (19.237%), Fusobacterium (12.408%), Lachnospira (3.811%), and Escherichia-Shigella (3.126%). Spearman correlation analysis results indicated that Fusobacterium_mortiferum, Fusobacterium, and Gammaproteobacteria were positively correlated with TNF-α (p < 0.05), whereas Ruminococcaceae, Bacteroidales was negatively correlated with TNF-α (p < 0.05). Additionally, Agathobacter was positively correlated with contents of IL-2 and IL-8 (p < 0.05), whereas Prevotellaceae, and Prevotella were negatively correlated with IL-8 content (p < 0.05). Furthermore, the top five strains in the CD4 high group (≥350/mm) included Bacteroides (23.286%), Prevotella (21.943%), Fusobacterium (10.479%), Lachnospira (4.465%), and un_f_Lachnospiraceae (2.786%). Taken together, the present study identified that Fusobacterium and Escherichia-Shigella were specific and highly abundant in the HIV group and a correlation between the different bacterial flora and the contents of IL-2, IL-8, and TNF-α was revealed.
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http://dx.doi.org/10.1080/21655979.2021.2019174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974104PMC
February 2022

CircVPS13C promotes pituitary adenoma growth by decreasing the stability of IFITM1 mRNA via interacting with RRBP1.

Oncogene 2022 03 28;41(11):1550-1562. Epub 2022 Jan 28.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

CircRNAs play important roles in a variety of biological processes by acting as microRNA sponges and protein scaffolds or by encoding functional proteins. However, their functions and underlying mechanisms remain largely unknown. Distinctive circRNA patterns were explored by comparing nonfunctioning pituitary adenomas (NFPAs) and normal pituitary tissues with a circRNA array. The biological functions of selected circRNAs were determined in vitro and in vivo. RNA-seq and circRNA pulldown assays were applied to investigate the underlying mechanisms. The circRNA profile of NFPAs is tremendously different from that of normal pituitary tissues. CircVPS13C is significantly upregulated in NFPA samples and cell lines. Gain- and loss-of-function experiments demonstrate that silencing circVPS13C inhibits the proliferation of pituitary tumor cells in vitro and in vivo. Mechanistically, circVPS13C silencing increases the expression of IFITM1 and subsequently activates its downstream genes involved in MAPK- and apoptosis-associated signaling pathways. Rescue experiments show that IFITM1 overexpression partly reverses the biological effects of circVPS13C. Further studies reveal that circVPS13C inhibits IFITM1 expression through a novel mechanism mainly by competitively interacting with RRBP1, a ribosome-binding protein of the endoplasmic reticulum membrane, and thereby alleviating the stability of IFITM1 mRNA. Clinically, circVPS13C expression is markedly higher in high-risk NFPA samples and is downregulated in patient serum 7 days post-transsphenoidal adenoma resection. Our findings suggest that circVPS13C is a critical regulator in the proliferation and development of NFPAs through a novel mechanism, whereby regulating mRNA stability via interacting with ribosome-binding proteins on the endoplasmic reticulum membrane.
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http://dx.doi.org/10.1038/s41388-022-02186-0DOI Listing
March 2022

Potential-Driven Electrochemical Clearing of Ex Vivo Alkaline Corneal Injuries.

Transl Vis Sci Technol 2022 01;11(1):32

Beckman Laser Institute & Medical Clinic, University of California-Irvine, Irvine, CA, USA.

Purpose: Corneal chemical injuries (CCI) obscure vision by opacifying the cornea; however, current treatments may not fully restore clarity. Here, we investigated potential-driven electrochemical treatment (P-ECT) to restore clarity after alkaline-based CCI in ex vivo rabbit corneas and examined collagen fiber orientation changes using second harmonic generation (SHG).

Methods: NaOH was applied to the corneas of intact New Zealand white rabbit globes. P-ECT was performed on the opacified cornea while optical coherence tomography (OCT) imaging (∼35 frames per second) was simultaneously performed. SHG imaging evaluated collagen fiber structure before NaOH application and after P-ECT. Irrigation with water served as a control.

Results: P-ECT restored local optical clarity after NaOH exposure. OCT imaging shows both progression of NaOH injury and the restoration of clarity in real time. Analysis of SHG z-stack images show that collagen fibril orientation is similar between control, NaOH-damaged, and post-P-ECT corneas. NaOH-injured corneas flushed with water (15 minutes) show no restoration of clarity.

Conclusions: P-ECT may be a means to correct alkaline CCI. Collagen fibril orientation does not change after NaOH exposure or P-ECT, suggesting that no irreversible matrix level fiber changes occur. Further studies are required to determine the mechanism for corneal clearing and to ascertain the optimal electrical dosimetry parameters and electrode designs.

Translational Relevance: Our findings suggest that P-ECT is a potentially effective, low-cost treatment for alkaline CCI.
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http://dx.doi.org/10.1167/tvst.11.1.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787648PMC
January 2022

Establishment of a human induced pluripotent stem cell line (CSUASOi008-A) from a type 2 diabetic patient with retinopathy.

Stem Cell Res 2021 Dec 21;59:102637. Epub 2021 Dec 21.

Aier School of Ophthalmology, Central South University, P.R.C., 18th Floor, the New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Aier Eye Institute, 18th Floor, The New Century Building, #198 Furong Middle Road, Changsha, Hunan 410015, China; Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China; Institute of Ophthalmology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address:

Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, and the leading cause of preventable blindness in working-aged people. Here, we generated an induced pluripotent stem (iPS) cell line using blood-derived cells from a patient with DR. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with Sendai virus.
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http://dx.doi.org/10.1016/j.scr.2021.102637DOI Listing
December 2021

Research on Taproots Identification Technology in Quality Intelligent Management System.

Comput Intell Neurosci 2021 16;2021:8292535. Epub 2021 Sep 16.

School of Mechanical and Electrical Engineering, Kunming University of Science and Technology, Kunming 650500, China.

In the quality intelligent management system, the big roots and fibrous roots cannot be cut automatically because the machine cannot distinguish the taproot, big roots, and fibrous roots of , resulting in the automatic cutting mechanism unable to obtain the control trajectory coordinate reference of the tool feed. To solve this problem, this paper proposes a visual optimal network model detection method, which uses the image detection method of marking anchor frames to improve the detection accuracy. A variety of deep learning network models are modified by the TensorFlow framework, and the best training model is optimized by comparing the results of training, testing, and verification data. This model is used to automatically identify the taproots and provide the control trajectory coordinate reference for the actuator that cuts big roots and fibrous roots automatically. The experimental results show that the optimal network model studied in this paper is effective and accurate in identifying the taproots of .
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http://dx.doi.org/10.1155/2021/8292535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463189PMC
September 2021

Guideline conformity to the Stupp regimen in patients with newly diagnosed glioblastoma multiforme in China.

Future Oncol 2021 Nov 14;17(33):4571-4582. Epub 2021 Sep 14.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100010, China.

To determine how consistently Chinese glioblastoma multiforme (GBM) patients were treated according to the Stupp regimen. The proportion of treatments conforming to the Stupp regimen and reasons for nonconformity were evaluated in 202 newly diagnosed GBM patients. Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations were temozolomide dosages >75 mg/m (58/120; 48.3%) and treatment durations <42 days (84/120; 70.0%) in the concomitant phase and temozolomide dosages <150 mg/m (89/101; 88.1%) in the maintenance phase. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments. Increased conformity to the Stupp regimen is needed for GBM patients in China.
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http://dx.doi.org/10.2217/fon-2021-0435DOI Listing
November 2021

An automated ASPECTS method with atlas-based segmentation.

Comput Methods Programs Biomed 2021 Oct 31;210:106376. Epub 2021 Aug 31.

Laboratory of Image Science and Technology, Southeast University, Nanjing 210096, China; Key Laboratory of Computer Network and Information Integration (Southeast University), Ministry of Education, Nanjing 210096, China. Electronic address:

Background And Purpose: As a simple and reliable systematic method to evaluate the early ischemic changes in the blood supply region of the middle cerebral artery of patients with ischemic stroke, the Alberta Stroke Program Early CT score (ASPECTS) can be used for rapid semi-quantitative evaluation of ischemic lesions, which is helpful to select potential candidates for intravenous and intra-arterial therapies, determine the thrombolytic effect and long-term prognosis. This method mainly relies on doctors' visual observation. However, due to different levels of doctor's experience, the poor inter-reader agreement may result in errors in the final ASPECTS. The purpose of this work was to propose an automated semi-quantitative method for the diagnosis of acute ischemic stroke based on non-contrast computed tomography (NCCT), to provide a reference for doctors in the diagnosis and evaluation.

Methods: NCCT data from a total of 90 patients were included for auto-ASPECTS training and testing. After preprocessing CT images, the regions of interest (ROI) for ASPECTS were labeled using atlas-based segmentation. The mean difference, mean ratio and brain density shifts (BDS) of the corresponding regions of the contralateral brain were used as the standard for quantitative analysis. The auto-ASPECTS method was developed and validated to predict early ischemic changes whose performance was evaluated by the agreement (accuracy) of predictions and consensus scores of two observers.

Results: A comparison was made among the results on mean difference, mean ratio, BDS and the combination of multiple parameters as the standard. The result of using BDS alone was relatively better than the result of using any other parameter alone or any combination of multiple parameters, and accuracy in the test set was 0.80. In the test set, accuracy with using different BDS thresholds increased by 6.67% compared with using the consistent BDS threshold. After dichotomy of auto-ASPECTS and consensus scores with the threshold of 7, the agreement of them was 83.3% and there was no significant difference between the two distributions (p = 0.344) in McNemar test.

Conclusions: The proposed auto-ASPECTS method for NCCT images can provide useful information for early diagnosis and evaluation of patients with acute ischemic stroke (AIS).
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http://dx.doi.org/10.1016/j.cmpb.2021.106376DOI Listing
October 2021

Surface kinematic and depth-resolved analysis of human vocal folds in vivo during phonation using optical coherence tomography.

J Biomed Opt 2021 08;26(8)

University of California, Irvine Medical Center, Department of Otolaryngology-Head and Neck Surgery,, United States.

Significance: The human vocal fold (VF) oscillates in multiple vectors and consists of distinct layers with varying viscoelastic properties that contribute to the mucosal wave. Office-based and operative laryngeal endoscopy are limited to diagnostic evaluation of the VF epithelial surface only and are restricted to axial-plane characterization of the horizontal mucosal wave. As such, understanding of the biomechanics of human VF motion remains limited.

Aim: Optical coherence tomography (OCT) is a micrometer-resolution, high-speed endoscopic imaging modality which acquires cross-sectional images of tissue. Our study aimed to leverage OCT technology and develop quantitative methods for analyzing the anatomy and kinematics of in vivo VF motion in the coronal plane.

Approach: A custom handheld laryngeal stage was used to capture OCT images with 800 A-lines at 250 Hz. Automated image postprocessing and analytical methods were developed.

Results: Novel kinematic analysis of in vivo, long-range OCT imaging of the vibrating VF in awake human subjects is reported. Cross-sectional, coronal-plane panoramic videos of the larynx during phonation are presented with three-dimensional videokymographic and space-time velocity analysis of VF motion.

Conclusions: Long-range OCT with automated computational methods allows for cross-sectional dynamic laryngeal imaging and has the potential to broaden our understanding of human VF biomechanics and sound production.
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http://dx.doi.org/10.1117/1.JBO.26.8.086005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374544PMC
August 2021

The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis.

Oncogene 2021 07 9;40(26):4453-4467. Epub 2021 Jun 9.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.
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http://dx.doi.org/10.1038/s41388-021-01854-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249232PMC
July 2021

Identify glioma recurrence and treatment effects with triple-tracer PET/CT.

BMC Med Imaging 2021 05 31;21(1):92. Epub 2021 May 31.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.

Background: Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, N-NH, F-FDOPA, and F-FDG, to identify TuR and TrE in glioma patients following treatment.

Methods: Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months.

Results: In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of N-NH and F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (N-NH 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of N-NH and F-FDOPA were significantly higher in TuR than in TrE group (N-NH 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for N-NH; 84.6%, 100% and 0.938, for F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively.

Conclusion: Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, F-FDOPA PET-CT is the most reliable. The combination of F-FDOPA and N-NH does not increase the diagnostic efficiency, while F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.
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http://dx.doi.org/10.1186/s12880-021-00624-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165792PMC
May 2021

1.7-Micron Optical Coherence Tomography Angiography for Characterization of Skin Lesions-A Feasibility Study.

IEEE Trans Med Imaging 2021 09 31;40(9):2507-2512. Epub 2021 Aug 31.

Optical coherence tomography (OCT) is a non-invasive diagnostic method that offers real-time visualization of the layered architecture of the skin in vivo. The 1.7-micron OCT system has been applied in cardiology, gynecology and dermatology, demonstrating an improved penetration depth in contrast to conventional 1.3-micron OCT. To further extend the capability, we developed a 1.7-micron OCT/OCT angiography (OCTA) system that allows for visualization of both morphology and microvasculature in the deeper layers of the skin. Using this imaging system, we imaged human skin with different benign lesions and described the corresponding features of both structure and vasculature. The significantly improved imaging depth and additional functional information suggest that the 1.7-micron OCTA system has great potential to advance both dermatological clinical and research settings for characterization of benign and cancerous skin lesions.
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http://dx.doi.org/10.1109/TMI.2021.3081066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834583PMC
September 2021

Graph-based rotational nonuniformity correction for localized compliance measurement in the human nasopharynx.

Biomed Opt Express 2021 Apr 30;12(4):2508-2518. Epub 2021 Mar 30.

Beckman Laser Institute, University of California, Irvine, Irvine, CA 92612, USA.

Recent advancements in the high-speed long-range optical coherence tomography (OCT) endoscopy allow characterization of tissue compliance in the upper airway, an indicator of collapsibility. However, the resolution and accuracy of localized tissue compliance measurement are currently limited by the lack of a reliable nonuniform rotational distortion (NURD) correction method. In this study, we developed a robust 2-step NURD correction algorithm that can be applied to the dynamic OCT images obtained during the compliance measurement. We demonstrated the utility of the NURD correction algorithm by characterizing the local compliance of nasopharynx from an awake human subject for the first time.
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http://dx.doi.org/10.1364/BOE.419997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086476PMC
April 2021

Integrated pulse scope for tunable generation and intrinsic characterization of structured femtosecond laser.

Sci Rep 2021 May 6;11(1):9670. Epub 2021 May 6.

Beckman Laser Institute, University of California, Irvine, Irvine, CA, 92617, USA.

Numerous techniques have been demonstrated for effective generation of orbital angular momentum-carrying radiation, but intracavity generation of continuously tunable pulses in the femtosecond regime remains challenging. Even if such a creation was realized, the generated pulses-like all pulses in reality-are complex and transitory objects that can only be comprehensively characterized via multidimensional spaces. An integrated lasing system that generates pulses while simultaneously quantifies them can achieve adaptive pulse tailoring. Here, we report a femtosecond pulse scope that unifies vector vortex mode-locked lasing and vectorial quantification. With intracavity-controlled Pancharatnam-Berry phase modulation, continuous and ergodic generation of spirally polarized states along a broadband higher-order Poincaré sphere was realized. By intrinsically coupling a two-dimensional polarization-sensitive time-scanning interferometer to the laser, multidimensional spatiotemporal features of the pulse were further visualized. The proposed methodology paves the way for design optimization of ultrafast optics by integrating complex femtosecond pulse generation and structural customization, facilitating its applications in optical physics research and laser-based manufacturing.
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http://dx.doi.org/10.1038/s41598-021-87938-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102529PMC
May 2021

Alendronate-functionalized hypoxia-responsive polymeric micelles for targeted therapy of bone metastatic prostate cancer.

J Control Release 2021 06 29;334:303-317. Epub 2021 Apr 29.

Institute of Special Environmental Medicine, Nantong University, Nantong, People's Republic of China. Electronic address:

Bone metastasis is one of the leading causes of cancer-related death and remains incurable in spite of great efforts. Bone-targeted nanoparticle-based drug carriers can overcome the difficulties in delivering therapeutic agents to metastatic bone and endowing them with a stimuli-responsive feature for controllable drug release can further maximize their therapeutic outcome. In light of hypoxic microenvironment of bone metastasis, we herein reported a bone-targeted and hypoxia-responsive polymeric micelle system for effective treatment of bone metastatic prostate cancer. The micelles were self-assembled from a polyethylene glycol and poly-l-lysine based copolymer using alendronate as a bone-targeted moiety and azobenzene as a hypoxia-responsive linker, showing a high affinity to metastatic bone and a high sensitivity in responding to hypoxia in vitro. In vivo studies further showed that after a selective accumulation in metastatic bone, the micelles could respond to hypoxic bone metastasis for rapid drug release to an effective therapeutic dosage. As a result, the micelles could suppress tumor growth in bone and inhibit bone destruction by inhibiting osteoclast activity and promoting osteoblast activity, achieving an enhanced therapeutic outcome with relieved bone pain and prolonged survival time. Bone-targeted and hypoxia-responsive nanocarriers therefore represent a promising advancement for treating bone metastasis. To our best knowledge, it might be the first example of the application of hypoxia-responsive nanocarriers in treating bone metastasis.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.035DOI Listing
June 2021

Dysbiosis and Implication of the Gut Microbiota in Diabetic Retinopathy.

Front Cell Infect Microbiol 2021 19;11:646348. Epub 2021 Mar 19.

Aier School of Ophthalmology, Central South University, Changsha, China.

The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The and diversities in both the DM and DR groups were reduced compared with those in the HC group. was the most abundant genus, especially in the DM group. In addition, increased levels of and and decreased levels of , and genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, , which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.
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http://dx.doi.org/10.3389/fcimb.2021.646348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017229PMC
July 2021

CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas.

Front Cell Dev Biol 2021 19;9:653240. Epub 2021 Mar 19.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Proteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.

Methods: The genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.

Results: The CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.

Conclusion: This study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.653240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009185PMC
March 2021
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