Publications by authors named "Ming Hu"

855 Publications

M2 Macrophage-derived exosomal miR-501 contributes to pubococcygeal muscle regeneration.

Int Immunopharmacol 2021 Oct 8;101(Pt B):108223. Epub 2021 Oct 8.

Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China. Electronic address:

Pubococcygeal muscle injury can lead to stress urinary incontinence (SUI). M2 macrophages play a crucial role in myoblast differentiation during injured muscle regeneration. However, the underlying mechanism remains unclear. Recently, exosomes have attracted increasing attention due to their mediation of cell-to-cell communication. In this study, we found that M2 macrophages extensively infiltrated the pubococcygeal muscle on day 5 after injury (VD5) in vivo. Then, C2C12 myoblasts were treated with M2 macrophage-derived exosomes (M2-EXO) and the results revealed that these exosomes could promote myotube formation. MiR-501 was identified as one of the abundant microRNAs (miRNAs) selectively loaded in M2-EXO, and subsequently confirmed to promote C2C12 myoblast differentiation by targeting YY1. Moreover, in vivo experiments showed that M2-EXO improves the inflammatory cell infiltration and have a therapeutic effect on damaged pubococcygeal muscle in SUI models. Collectively, our present results provide new insights into the promyogenic mechanism of M2 macrophages and prove that M2 macrophage exosomal miR-501 may represent a potential therapeutic to promote recovery from diseases caused by muscle injury, including SUI.
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http://dx.doi.org/10.1016/j.intimp.2021.108223DOI Listing
October 2021

Cost-Effectiveness Analysis of Ultrasound Screening for Thyroid Cancer in Asymptomatic Adults.

Front Public Health 2021 22;9:729684. Epub 2021 Sep 22.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

This study evaluated the long-term cost-effectiveness of ultrasound screening for thyroid cancer compared with non-screening in asymptomatic adults. Applying a Markov decision-tree model with effectiveness and cost data from literature, we compared the long-term cost-effectiveness of the two strategies: ultrasound screening and non-screening for thyroid cancer. A one-way sensitivity analysis and a probabilistic sensitivity analysis were performed to verify the stability of model results. The cumulative cost of screening for thyroid cancer was $18,819.24, with 18.74 quality-adjusted life years (QALYs), whereas the cumulative cost of non-screening was $15,864.28, with 18.71 QALYs. The incremental cost-effectiveness ratio of $106,947.50/QALY greatly exceeded the threshold of $50,000. The result of the one-way sensitivity analysis showed that the utility values of benign nodules and utility of health after thyroid cancer surgery would affect the results. Ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness compared with non-screening. The optimized thyroid screening strategy for a specific population is essential.
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http://dx.doi.org/10.3389/fpubh.2021.729684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494179PMC
September 2021

Human Cytomegalovirus Infection Activates Glioma Activating Transcription Factor 5 via microRNA in a Stress-Induced Manner.

ACS Chem Neurosci 2021 Oct 7. Epub 2021 Oct 7.

Department of Natural Sciences, College of Science and Health Professions, Northeastern State University, Broken Arrow, Oklahoma 74014, United States.

Human cytomegalovirus (HCMV) harnesses a cell-specific manner to infect human nervous system cancer cells, establishes a life-long persistent infection without cell death, and modulates signaling pathways associated with cancer. We previously identified that the HCMV immediate-early 2 (IE2-86) protein binds and activates activating transcription factor 5 (ATF5), a survival factor in many tumor cells. In this study, we investigated a new mechanism of stress-induced miRNA regulation at the ATF5 3' UTR under the HCMV infection and other cellular stress conditions. We employed RNA-Seq and in silico analysis to screen stress response gene sets and identify miRNA candidates as potential regulators of ATF5 following HCMV infection. We found that ATF5 and cellular stress response genes were significantly upregulated under HCMV infection and diverse stress conditions. Three downregulated miRNAs were filtrated based on our threshold, and their binding sites for 3' UTR of ATF5 were predicted. Then, luciferase reporter assays were carried out to verify the binding sites for all three miRNA candidates targeting ATF5. However, in vitro validation has shown that miR-134-5p is the only candidate that can reverse the ATF5 protein upregulation under infection and other cell stresses. Additionally, miR-134-5p levels were significantly reduced and inversely related to ATF5 mRNA under HCMV infection. These results provide new evidence that quiescent HCMV infection can trigger a stress response in glioma cells and modulate ATF5 levels by downregulating specific miRNA.
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http://dx.doi.org/10.1021/acschemneuro.1c00576DOI Listing
October 2021

Delayed Initiation of ECMO Is Associated With Poor Outcomes in Patients With Severe COVID-19: A Multicenter Retrospective Cohort Study.

Front Med (Lausanne) 2021 16;8:716086. Epub 2021 Sep 16.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.

Extracorporeal membrane oxygenation (ECMO) is a rapidly evolving therapy for acute lung and/or heart failure. However, the information on the application of ECMO in severe coronavirus disease 2019 (COVID-19) is limited, such as the initiation time. Especially in the period and regions of ECMO instrument shortage, not all the listed patients could be treated with ECMO in time. This study aimed to investigate and clarify the timing of ECMO initiation related to the outcomes of severe patients with COVID-19. The results show that ECMO should be initiated within 24 h after the criteria are met. In this retrospective, multicenter cohort study, we enrolled all ECMO patients with confirmed COVID-19 at the three hospitals between December 29, 2019 and April 5, 2020. Data on the demographics, clinical presentation, laboratory profile, clinical course, treatments, complications, and outcomes were collected. The primary outcomes were successful ECMO weaning rate and 60-day mortality after ECMO. Successful weaning from ECMO means that the condition of patients improved with adequate oxygenation and gas exchange, as shown by the vital signs, blood gases, and chest X-ray, and the patient was weaned from ECMO for at least 48 h. A total of 31 patients were included in the analysis. The 60-day mortality rate after ECMO was 71%, and the ECMO weaning rate was 26%. Patients were divided into a delayed ECMO group [3 (interquartile range (IQR), 2-5) days] and an early ECMO group [0.5 (IQR, 0-1) days] based on the time between meeting the ECMO criteria and ECMO initiation. In this study, 14 and 17 patients were included in the early and delayed treatment groups, respectively. Early initiation of ECMO was associated with decreased 60-day mortality after ECMO (50 vs. 88%, = 0.044) and an increased ECMO weaning rate (50 vs. 6%, = 0.011). In ECMO-supported patients with COVID-19, delayed initiation of ECMO is a risk factor associated with a poorer outcome. Clinical trial submission: March 19, 2020. Registry name: A medical records-based study for the clinical application of extracorporeal membrane oxygenation in the treatment of severe respiratory failure patients with novel coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.aspx?proj=51267,identifier:~ChiCTR2000030947.
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http://dx.doi.org/10.3389/fmed.2021.716086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481658PMC
September 2021

Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer.

Front Genet 2021 9;12:675197. Epub 2021 Sep 9.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.

DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC). DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features. We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC. The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.
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http://dx.doi.org/10.3389/fgene.2021.675197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458765PMC
September 2021

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

J Pain Symptom Manage 2021 Sep 23. Epub 2021 Sep 23.

Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou China. Electronic address:

Context: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy.

Objectives: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients.

Methods: In this open-label, multi-center, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga.

Results: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 versus 45.37±8.61, p=0.039). EA treatment also produced ESAS relief at the end of intervention (14.36±12.28 versus 23.91±15.52, p=0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% versus 15.79%, p=0.031) and neutropenia (2.56% versus 26.31%, p=0.012).

Conclusions: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.09.009DOI Listing
September 2021

HPRep: Quantifying Reproducibility in HiChIP and PLAC-Seq Datasets.

Curr Issues Mol Biol 2021 Sep 17;43(2):1156-1170. Epub 2021 Sep 17.

Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27516, USA.

HiChIP and PLAC-Seq are emerging technologies for studying genome-wide long-range chromatin interactions mediated by the protein of interest, enabling more sensitive and cost-efficient interrogation of protein-centric chromatin conformation. However, due to the unbalanced read distribution introduced by protein immunoprecipitation, existing reproducibility measures developed for Hi-C data are not appropriate for the analysis of HiChIP and PLAC-Seq data. Here, we present HPRep, a stratified and weighted correlation metric derived from normalized contact counts, to quantify reproducibility in HiChIP and PLAC-Seq data. We applied HPRep to multiple real datasets and demonstrate that HPRep outperforms existing reproducibility measures developed for Hi-C data. Specifically, we applied HPRep to H3K4me3 PLAC-Seq data from mouse embryonic stem cells and mouse brain tissues as well as H3K27ac HiChIP data from human lymphoblastoid cell line GM12878 and leukemia cell line K562, showing that HPRep can more clearly separate among pseudo-replicates, real replicates, and non-replicates. Furthermore, in an H3K4me3 PLAC-Seq dataset consisting of 11 samples from four human brain cell types, HPRep demonstrated the expected clustering of data that could not be achieved by existing methods developed for Hi-C data, highlighting the need for a reproducibility metric tailored to HiChIP and PLAC-Seq data.
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http://dx.doi.org/10.3390/cimb43020082DOI Listing
September 2021

Tunable Circularly Polarized Luminescence from Single Crystal and Powder of the Simplest Tetraphenylethylene Helicate.

ACS Nano 2021 Sep 21. Epub 2021 Sep 21.

Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Tetraphenylethylene and its derivatives are a class of aggregation-induced emission (AIE) compounds that are most extensively and successfully studied. It has been found that the simplest TPE is easy to crystallize into homochiral M crystals or P crystals. However, no research on circularly polarized luminescence (CPL) of TPE solid is documented. In this paper, we report that TPE can grow into big and nonefflorescent single crystals in single helical conformation and has large birefringence that is comparative with commercially available products. The TPE single crystals can emit strong CPL with a very high value up to 0.53. Moreover, the sense and magnitude of CPL signals can be willfully tuned by simple rotation of the single crystal due to anisotropy of the crystals. This simple and promising CPL photonic material integrates emission, chirality, and birefringence together in one single crystal without needing an additional chiral dopant or conjugate polymer that can produce linearly polarized light. After being ground into fine powder and pressed as KBr pellets, the obtained nanocrystals of TPE also emit strong CPL light. Exceptionally, by mixing other achiral luminescent dyes together with TPE powder in KBr pellets, induced CPL signals were obtained, which could give full-color CPL emission. Although there were no interactions between TPE and the dyes in the pellets, induced CPL signals were realized through radiative energy transfer, providing a very simple method for the tuning of CPL emission.
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http://dx.doi.org/10.1021/acsnano.1c06644DOI Listing
September 2021

Clinical application of traditional Chinese medicine moisture exposed burn ointment in the treatment of facial soft tissue defect.

J Cosmet Dermatol 2021 Sep 18. Epub 2021 Sep 18.

Department of Stomatology, Ankang Hospital of Traditional Chinese Medicine, Shaanxi Ankang, China.

Objective: To introduce a new method of treating facial soft tissue defect by observing the clinical curative effects of traditional Chinese medicine moisture exposed burn ointment in treating facial soft tissue defect.

Methods: A total of 85 patients with facial soft tissue defects were treated with traditional Chinese medicine moisture exposed burn ointment, and the clinical therapeutic effects were analyzed by observing the wound healing time, scar formation and changes of facial appearance and functions.

Results: Of the 85 patients, the shortest wound healing time was 12 days and the longest was 72 days; the facial appearance and functions restored to be normal in 74 patients, with good skin elasticity and mild scar formation in the wound area; 11 patients were lost to the follow-up; two patients suffered from the longest wound healing time due to their skin defect of nasal tip and nasal columella and the cartilage defect of nasal wings, and V-shaped defects were left at the edge of the left nostrils after the wound healing, which may be attributed to the ineffectiveness of MEBT/MEBO on cartilage.

Conclusion: Traditional Chinese medicine moisture exposed burn ointment can realize more satisfying healing effects when applied in the treatment of facial soft tissue defects, including user-friendly operation, no special requirements for medical devices, obviously lower treatment cost, etc., and thus it is an easy-to-operate and effective way for such patients, especially for elderly patients, patients with poor body conditions and patients unbearable to undergo complicated operations.
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http://dx.doi.org/10.1111/jocd.14404DOI Listing
September 2021

Superstructured mesocrystals through multiple inherent molecular interactions for highly reversible sodium ion batteries.

Sci Adv 2021 Sep 8;7(37):eabh3482. Epub 2021 Sep 8.

BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, College of Materials Science and Engineering, Sichuan University, Chengdu Sichuan 610065, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abh3482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442931PMC
September 2021

Reliable sensory processing in mouse visual cortex through cooperative interactions between somatostatin and parvalbumin interneurons.

J Neurosci 2021 Sep 7. Epub 2021 Sep 7.

Picower Institute for Learning and Memory

Intrinsic neuronal variability significantly limits information encoding in the primary visual cortex (V1). However, under certain conditions, neurons can respond reliably with highly precise responses to the same visual stimuli from trial to trial. This suggests that there exist intrinsic neural circuit mechanisms that dynamically modulate the inter-trial variability of visual cortical neurons. Here, we sought to elucidate the role of different inhibitory interneurons in reliable coding in mouse V1. To study the interactions between somatostatin-expressing (SST) and parvalbumin-expressing (PV) interneurons, we used a dual-color calcium imaging technique that allowed us to simultaneously monitor these two neural ensembles while awake mice, of both sexes, passively viewed natural movies. SST neurons were more active during epochs of reliable pyramidal neuron firing whereas PV neurons were more active during epochs of unreliable firing. SST neuron activity lagged that of PV neurons, consistent with a feedback inhibitory SST→PV circuit. To dissect the role of this circuit in pyramidal neuron activity, we used temporally limited optogenetic activation and inactivation of SST and PV interneurons during periods of reliable and unreliable pyramidal cell firing. Transient firing of SST neurons increased pyramidal neuron reliability by actively suppressing PV neurons, a proposal that was supported by a rate-based model of V1 neurons. These results identify a cooperative functional role for the SST→PV circuit in modulating the reliability of pyramidal neuron activity.Cortical neurons often respond to identical sensory stimuli with large variability. However, under certain conditions, the same neurons can also respond highly reliably. The circuit mechanisms that contribute to this modulation remain unknown. Here we used novel dual-wavelength calcium imaging and temporally selective optical perturbation to identify an inhibitory neural circuit in visual cortex that can modulate the reliability of pyramidal neurons to naturalistic visual stimuli. Our results, supported by computational models, suggest that somatostatin interneurons increase pyramidal neuron reliability by suppressing parvalbumin interneurons via the inhibitory SST→PV circuit. These findings reveal a novel role of the SST→PV circuit in modulating the fidelity of neural coding critical for visual perception.
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http://dx.doi.org/10.1523/JNEUROSCI.3176-20.2021DOI Listing
September 2021

MUNIn: A statistical framework for identifying long-range chromatin interactions from multiple samples.

HGG Adv 2021 Jul 23;2(3). Epub 2021 May 23.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

Chromatin spatial organization (interactome) plays a critical role in genome function. Deep understanding of chromatin interactome can shed insights into transcriptional regulation mechanisms and human disease pathology. One essential task in the analysis of chromatin interactomic data is to identify long-range chromatin interactions. Existing approaches, such as HiCCUPS, FitHiC/FitHiC2, and FastHiC, are all designed for analyzing individual cell types or samples. None of them accounts for unbalanced sequencing depths and heterogeneity among multiple cell types or samples in a unified statistical framework. To fill in the gap, we have developed a novel statistical framework MUNIn (multiple-sample unifying long-range chromatin-interaction detector) for identifying long-range chromatin interactions from multiple samples. MUNIn adopts a hierarchical hidden Markov random field (H-HMRF) model, in which the status (peak or background) of each interacting chromatin loci pair depends not only on the status of loci pairs in its neighborhood region but also on the status of the same loci pair in other samples. To benchmark the performance of MUNIn, we performed comprehensive simulation studies and real data analysis and showed that MUNIn can achieve much lower false-positive rates for detecting sample-specific interactions (33.1%-36.2%), and much enhanced statistical power for detecting shared peaks (up to 74.3%), compared to uni-sample analysis. Our data demonstrated that MUNIn is a useful tool for the integrative analysis of interactomic data from multiple samples.
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http://dx.doi.org/10.1016/j.xhgg.2021.100036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415461PMC
July 2021

Pharmacokinetic Characterization and Bioavailability Barrier for the Key Active Components of Botanical Drug Antitumor B (ATB) in Mice for Chemoprevention of Oral Cancer.

J Nat Prod 2021 Sep 31;84(9):2486-2495. Epub 2021 Aug 31.

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77004, United States.

This study aims to characterize the pharmacokinetic (PK) profiles and identify important bioavailability barriers and pharmacological pathways of the key active components (KACs) of Antitumor B (ATB), a chemopreventive agent. KACs (matrine, dictamine, fraxinellone, and maackiain) of ATB were confirmed using the antiproliferative assay and COX-2 inhibition activities in oral cancer cells. The observed activities of KACs were consistent with their cell signaling pathways predicted using the network pharmacology approach. The pharmacokinetics of KACs were determined after i.v., i.p., and p.o. delivery using ATB extract and a mixture of four KACs in mice. Despite good solubilities and permeabilities, poor oral bioavailabilities were estimated for all KACs, mostly because of first-pass metabolism in the liver (for all KACs) and intestines (for matrine and fraxinellone). Multiple-dose PK studies showed 23.2-fold and 8.5-fold accumulation of dictamine and maackiain in the blood, respectively. Moreover, saliva levels of dictamine and matrine were found significantly higher than their blood levels. In conclusion, the systemic bioavailabilities of ATB-KACs were low, but significant levels of dictamine and matrine were found in saliva upon repeated oral administration. Significant salivary concentrations of matrine justified its possible use as a drug-monitoring tool to track patient compliance during chemoprevention trials.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00501DOI Listing
September 2021

SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data.

Nat Methods 2021 09 26;18(9):1056-1059. Epub 2021 Aug 26.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.
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http://dx.doi.org/10.1038/s41592-021-01231-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440170PMC
September 2021

M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis.

Cell Biol Int 2021 Aug 25. Epub 2021 Aug 25.

Department of Spine Surgery, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China.

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management.
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http://dx.doi.org/10.1002/cbin.11690DOI Listing
August 2021

Development of Rofecoxib-Based Fluorescent Probes and Investigations on Their Solvatochromism, AIE Activity, Mechanochromism, and COX-2-Targeted Bioimaging.

Anal Chem 2021 09 23;93(35):11991-12000. Epub 2021 Aug 23.

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77204, United States.

Cyclooxygenase-2 (COX-2) fluorescent probes are promising tools for early diagnosis of cancer. Traditionally, COX-2 probes were designed by connecting two parts, a fluorophore and a COX-2 binding unit, via a flexible linker. Herein, a new class of COX-2-specific fluorescent probes have been developed via one-step modification from rofecoxib by an integrative approach to combine the binding unit and the fluorophore into one. Among them, several new rofecoxib analogues not only exhibited still potent COX-2 binding ability but also exhibited attractive fluorescence properties, such as tunable blue-red emission, solvatochromism, aggression-induced emission behavior, and mechanochromism. Notably, the emission of can be switched between green-yellow in the crystalline state and red-orange in the amorphous state by grinding and fuming treatments. Furthermore, the highly fluorescent compound (Φ = 0.94 in powder) displayed a much stronger fluorescence imaging of COX-2 in HeLa cancer cells overexpressing COX-2 than RAW264.7 normal cells with a minimal expression of COX-2. Most importantly, can light up human cancer tissues from adjacent normal tissues with a much brighter fluorescence by targeting the COX-2 enzyme. These results demonstrated the potential of as a new red fluorescent probe for human cancer imaging in clinical applications.
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http://dx.doi.org/10.1021/acs.analchem.1c01978DOI Listing
September 2021

Systematic Review and Quality Evaluation of Pharmacoeconomic Studies on Traditional Chinese Medicines.

Front Public Health 2021 3;9:706366. Epub 2021 Aug 3.

West China School of Pharmacy, Sichuan University, Chengdu, China.

This study was aimed to find and appraise the available published pharmacoeconomic research on Traditional Chinese Medicine (TCM), to identify related issues and make suggestions for improvement in future research. After developing a search strategy and establishing inclusion and exclusion criteria, pharmacoeconomic studies on TCM were sourced from seven Chinese and English databases from inception to April 2020. Basic information about the studies and key pharmacoeconomic items of each study were extracted. The quality of each study was evaluated by using the British Medical Journal economic submissions checklist for authors and peer reviewers, focusing on factors such as study design, research time horizon, sample size, perspective, and evaluation methods. A total of 431 published pharmacoeconomic articles with 434 studies on topics including cost-effectiveness, cost-benefit, cost-minimization, cost-utility, or combination analyses were identified and included in this review. Of these, 424 were published in Chinese and 7 in English. These studies conducted economic evaluations of 264 Chinese patent medicines and 70 types of TCM prescriptions for 143 diseases, including those of the central nervous, cardiovascular, respiratory, gynecologyical, and other systems. The studied TCMs included blood-activating agents (such as Xuesaitong tablet, Fufant Danshen tablet, and Danhong Injection), blood circulation promoting agents (such as Shuxuetong injection, Rupixiao tablet, and Fufang Danshen injection), and other therapeutic agents. The overall quality score of the studies was 0.62 (range 0.38 to 0.85). The mean quality score of studies in English was 0.72, which was higher than that of studies in Chinese with 0.62. The quality of pharmacoeconomic studies on TCM was relatively, generally low. Major concerns included study design, inappropriate pharmacoeconomic evaluation, insufficient sample size, or non-scientific assessment. Enhanced methodological training and cooperation, the development of a targeted pharmacoeconomic evaluation guideline, and proposal of a reasonable health outcome index are warranted to improve quality of future studies.
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http://dx.doi.org/10.3389/fpubh.2021.706366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368976PMC
August 2021

Disordered farnesoid X receptor signaling is associated with liver carcinogenesis in Abcb11-deficient mice.

J Pathol 2021 Aug 19. Epub 2021 Aug 19.

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China.

ABCB11 encodes the bile salt export pump (BSEP), a key regulator in maintaining bile acid (BA) homeostasis. Although inherited ABCB11 mutations have previously been linked to primary liver cancer, whether ABCB11 deficiency leads to liver cancer remains unknown. Here, we analyzed ABCB11 mRNA expression levels in liver tumor specimens [29 with hepatocellular carcinoma (HCC), one with intrahepatic cholangiocarcinoma (ICC), and one with mixed HCC/ICC] with adjacent normal specimens and published human datasets. Liver tissues obtained from Abcb11-deficient (Abcb11 ) mice and wild-type mice at different ages were compared by histologic, RNA-sequencing, and BA analyses. ABCB11 was significantly downregulated in human liver tumors compared with normal controls. Abcb11 mice demonstrated progressive intrahepatic cholestasis and liver fibrosis, and spontaneously developed HCC and ICC over 12 months of age. Abcb11 deficiency increased BAs in the liver and serum in mice, most of which are farnesoid X receptor (FXR) antagonists/non-agonists. Accordingly, the hepatic expression and transcriptional activity of FXR were downregulated in Abcb11 mouse livers. Administration of the FXR agonist obeticholic acid reduced liver injury and tumor incidence in Abcb11 mice. In conclusion, ABCB11 is aberrantly downregulated and plays a vital role in liver carcinogenesis. The cholestatic liver injury and liver tumors developed in Abcb11 mice are associated with increased FXR antagonist BAs and thereby decreased activation of FXR. FXR activation might be a therapeutic strategy in ABCB11 deficiency diseases. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5780DOI Listing
August 2021

Elevated serum triglyceride levels at first prenatal visit is associated with the development of gestational diabetes mellitus.

Diabetes Metab Res Rev 2021 Aug 18:e3491. Epub 2021 Aug 18.

Department of Clinical Nutrition, Huadong Hospital, Fudan University, Shanghai, China.

Aims: While several studies have indicated that maternal serum lipid profiles are associated with the development of gestational diabetes mellitus (GDM), the results have been inconsistent. This study aimed to explore the relationship between maternal lipids profiles at first prenatal visit and GDM and determine the optimal cut-off values of possible trimester-specific variables in predicting GDM.

Materials And Methods: Clinical data of women with singleton pregnancies who delivered in Xinhua Hospital between January 2016 and January 2017 were collected from electronic databases. Multivariate logistic regression was used to determine the potential risk factors of GDM (specific to the trimester at first prenatal visit), including age, body mass index (BMI), and serum lipid profile and fasting plasma glucose (FPG) levels. The receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of significant variables.

Results: Among the 2191 pregnant women included, 315 (14.38%) were diagnosed with GDM. Of these, 880 (40.16%) had their first prenatal visit before 14 gestational weeks. Univariate and multivariate analyses showed that both FPG and triglyceride (TG) levels in the first and second trimesters were associated with a high risk of GDM (p < 0.05). The ROC curve showed that serum TG levels >1.235 mmol/L and >1.525 mmol/L in the first and second trimesters, respectively, were significantly associated with the development of GDM (p < 0.05).

Conclusions: TG levels at first prenatal visit is associated with GDM risk. Different TG cut-off values should be applied in the different trimesters of pregnancy for GDM screening.
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http://dx.doi.org/10.1002/dmrr.3491DOI Listing
August 2021

Cost-Effectiveness Analysis of Triple Combination Preparations in the Treatment of Moderate-to-Severe Chronic Obstructive Pulmonary Disease.

Front Public Health 2021 28;9:713258. Epub 2021 Jul 28.

West China School of Pharmacy, Sichuan University, Chengdu, China.

This study analyzed the long-term cost-effectiveness of fluticasone/umeclidinium/vilanterol triple combination (FF/UMEC/VI) vs. budesonide/formoterol double combination (BUD/FOR) in the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD) and provides evidence for COPD treatment decisions. From the perspective of the healthcare system, a Markov model was established that consists of four states-stable period, non-severely deteriorating period, severely deteriorating period, and death-according to real-world COPD progression. The model period comprises 6 months, with a cycle length of 14 years. The initial state, transition probabilities, costs, and utility data were collected from the FULFIL trial, published literature, hospital record surveys, and . The discount rate was 5%, and the threshold was set as the Chinese per capita GDP in 2020 (¥72,447). The cost, utility, transition probabilities, and discount rate were calculated through TreeagePro11 software. The results were analyzed one-way factor analysis and probability sensitivity analysis. The baseline study shows that the 14-year treatment for FF/UMEC/VI and BUD/FOR groups are ¥199,765.55 and ¥173,030.05 with effectiveness at 8.54 quality-adjusted life years (QALYs) and 7.73 QALYs, respectively. The incremental cost-effectiveness ratio is ¥33,006.80/QALY, which is below the threshold. A tornado diagram of a one-way sensitivity analysis shows that the top three factors that affected the results are the non-severe deterioration rates of FF/UMEC/VI, the cost of FF/UMEC/VI and the non-severe deterioration rates of BUD/FOR. Probabilistic sensitivity analysis shows that FF/UMEC/VI (compared to BUD/FOR) can be made cost-effective under the willingness-to-pay (WTP) threshold (¥38,000). Furthermore, the likelihood of cost-effectiveness increases with a higher WTP. Compared with the double combination (BUD/FOR), the triple combination (FF/UMEC/VI) is more cost-effective under the Chinese per capita GDP threshold.
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http://dx.doi.org/10.3389/fpubh.2021.713258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355539PMC
August 2021

Energetic Barriers of Gas Permeation across Nanoporous Graphene.

ACS Appl Mater Interfaces 2021 Aug 14;13(33):39701-39710. Epub 2021 Aug 14.

Department of Mechanical Engineering, University of South Carolina, Columbia, South Carolina 29208, United States.

Realizing membranes of atomic thickness functioning reliably constitutes a giant leap forward for a plethora of applications where the efficient separation of fluid constituents at the molecular level is critical. Here, by employing density functional theory, we explore the energy landscape of typical gas molecules attempting permeation through graphene nanopores and determine the minimum energy permeation pathways, based on the precise knowledge of the related molecular level interactions. With this approach we investigate two basic permeation routes: direct permeation and surface-based transport. We find that for subnanometer pores, the diffusion barrier of direct and surface transport depends on the pore chemical functionalization, while the molecule pore permeation barrier is independent of the gas-pore approach due to the overlap of surface and direct diffusion paths over the pore center. The overall minimum energy permeation pathway of He, H, CO, and CH molecules, across nanopores of different dimensions and chemical functionalization, defines the pore diameter (∼1.2 nm) below which effusion theory is inaccurate, as well as the critical pore diameter (∼0.8 nm) required to achieve positive permeation barriers driving molecular sieving. We determine that achieving positive permeation barriers required for high selectivity gas separation is inseparably combined with postpermeation desorption barriers due to attractive van der Waals interactions. The discovered permeation energetics are pore-molecule-specific and are incorporated into an analytical model extending existing theory. Our results provide a scientific background for rational pore design in graphene membranes, which can lead to gas separation at a commercially relevant performance level.
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http://dx.doi.org/10.1021/acsami.1c09229DOI Listing
August 2021

Proximity Ligation-Assisted ChIP-Seq (PLAC-Seq).

Methods Mol Biol 2021 ;2351:181-199

Ludwig Institute for Cancer Research, La Jolla, CA, USA.

Proximity ligation-assisted ChIP-Seq (PLAC-Seq), also known as HiChIP, is a method to detect and quantify chromatin contacts anchored at genomic regions bound by specific proteins or histone modifications. By combining in situ Hi-C and chromatin immunoprecipitation (ChIP) using antibodies against transcription factors (TFs) or histone marks of interest, the method achieves targeted interrogation of chromatin organization at a subset of genomic regions. PLAC-Seq is able to identify long-range chromatin interactions at kilobase-scale resolution with significantly reduced sequencing cost.
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http://dx.doi.org/10.1007/978-1-0716-1597-3_10DOI Listing
September 2021

Clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 with hypotension in China: a retrospective cohort study.

Ann Palliat Med 2021 Aug 5;10(8):8536-8546. Epub 2021 Aug 5.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Background: The characteristics of the coronavirus disease 2019 (COVID-19) patients with hypotension are still limited. We aim to describe the clinical features and outcomes of the patients.

Methods: This was a multicenter retrospective study of critically ill patients with COVID-19 from ICUs in 19 hospitals in China. All patients were followed up to day 28 or death, which came first. Clinical and outcome data were collected and analyzed. Patients were classified as early-onset or late-onset hypotension, and clinical characteristics and outcomes were compared.

Results: A total of 649 patients were included in the final analysis, and 240 (37.0%) were hypotension patients. The median age of hypotension patients was 67 years (IQR, 60-73 years), and 159 (66.2%) were male. 172 (71.7%) of the hypotension patients had at least one comorbidity. The 28-day mortality of the patients with hypotension was 85.4%, which was significantly higher than that of patients without hypotension. Compared with late-onset hypotension patients, the 28-day mortality of patients with early-onset hypotension was significantly higher (90.1% vs. 78.6%, P=0.02).

Conclusions: Approximately one third critically ill COVID-19 patients progressed to hypotension. The mortality was significantly higher in hypotension patients than that in patients without hypotension. Compared with patients with late-onset hypotension, the mortality of patients with early-onset hypotension was significantly higher.
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http://dx.doi.org/10.21037/apm-20-2172DOI Listing
August 2021

Glucuronides Hydrolysis by Intestinal Microbial -Glucuronidases (GUS) Is Affected by Sampling, Enzyme Preparation, Buffer pH, and Species.

Pharmaceutics 2021 Jul 8;13(7). Epub 2021 Jul 8.

Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.

Glucuronides hydrolysis by intestinal microbial -Glucuronidases (GUS) is an important procedure for many endogenous and exogenous compounds. The purpose of this study is to determine the impact of experimental conditions on glucuronide hydrolysis by intestinal microbial GUS. Standard probe 4-Nitrophenyl -D-glucopyranoside (pNPG) and a natural glucuronide wogonoside were used as the model compounds. Feces collection time, buffer conditions, interindividual, and species variations were evaluated by incubating the substrates with enzymes. The relative reaction activity of pNPG, reaction rates, and reaction kinetics for wogonoside were calculated. Fresh feces showed the highest hydrolysis activities. Sonication increased total protein yield during enzyme preparation. The pH of the reaction system increased the activity in 0.69-1.32-fold, 2.9-12.9-fold, and 0.28-1.56-fold for mouse, rat, and human at three different concentrations of wogonoside, respectively. The Vmax for wogonoside hydrolysis was 2.37 ± 0.06, 4.48 ± 0.11, and 5.17 ± 0.16 μmol/min/mg and Km was 6.51 ± 0.71, 3.04 ± 0.34, and 0.34 ± 0.047 μM for mouse, rat, and human, respectively. The inter-individual difference was significant (4-6-fold) using inbred rats as the model animal. Fresh feces should be used to avoid activity loss and sonication should be utilized in enzyme preparation to increase hydrolysis activity. The buffer pH should be appropriate according to the species. Inter-individual and species variations were significant.
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http://dx.doi.org/10.3390/pharmaceutics13071043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309147PMC
July 2021

Recomposition and storage of sunlight with intelligent phosphors for enhanced photosynthesis.

Dalton Trans 2021 Aug 9;50(32):11025-11029. Epub 2021 Aug 9.

Key Laboratory of Surface & Interface of Polymer Materials of Zhejiang Province, Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, China.

This work presents a smart solar energy regulation strategy using photon tunable long persistent phosphors as solar energy harvesting antennas to enhance overall sunlight utilization by photosynthetic organisms in multiple modes.
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http://dx.doi.org/10.1039/d1dt02207eDOI Listing
August 2021

Decision-Making Model of Product Modeling Big Data Design Scheme Based on Neural Network Optimized by Genetic Algorithm.

Authors:
Ming Hu

Comput Intell Neurosci 2021 29;2021:9315700. Epub 2021 Jul 29.

School of Art, Wuxi Taihu University, Wuxi, Jiangsu 214064, China.

At present, machine learning artificial neural network technology, as one of the core technologies of enterprises, has received unprecedented attention. This technology is widely used in automatic driving, pattern recognition, teaching aid, product modeling, and other fields. According to the development of product design, this paper analyzes the factors that affect the decision-making of product design. The neural network optimized by genetic algorithm is studied, and the technical analysis of neural network algorithm before and after optimization is mainly carried out. The basic process of product modeling design model based on image processing under the background of big data is introduced. The multidirectional group decision-making model of product modeling design scheme in big data cloud environment is constructed. The final decision model can improve the overall design efficiency, shorten the manufacturing period, and provide a new idea for product modeling design.
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http://dx.doi.org/10.1155/2021/9315700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346316PMC
August 2021

Protective effect and potential mechanism of Schwann cell-derived exosomes on mechanical damage of rat dorsal root ganglion cells.

J Obstet Gynaecol Res 2021 Oct 8;47(10):3691-3701. Epub 2021 Aug 8.

Dept. of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Pudendal nerve (PN) injury was one of the most important pathogenesis of stress urinary incontinence (SUI). Schwann cell (SC)-derived exosomes could promote axonal regeneration. Wnt protein could significantly promote axonal regeneration and participate in the regulation of proliferation and differentiation of neural stem cells. Therefore, we sought to determine whether SCs-derived exosomes might also protect against damaged dorsal root ganglion cells (DRGs) through the Wnt/β-catenin pathway.

Material And Methods: The DRGs injury model was fabricated using a four-point bending system. The exosomes were separated from the SCs supernatant. XAV939, which was a small molecule inhibitor, was used to inhibit the Wnt/β-catenin pathway. Next, Cell Counting Kit-8 (CCK8) kit was used to detect cell activity. We evaluated the proliferative activity of DRG cells using the cell cycle and apoptosis detection kit. We assessed the cell apoptotic rates through the Annexin V/PE double staining. Finally, we detect the expression of downstream proteins of Wnt/β-catenin pathway in DRG cells using western blotting.

Results: SC-derived exosomes had protective effects on DRGs after mechanical damage, which could promote cell proliferation, transition of the cell cycle to the G2 phase, and inhibit cell apoptosis. Exogenous administration of XAV939 suppressed the promoting effect of SCs -derived exosomes on DRG cells and the expression of downstream proteins of Wnt/β-catenin pathway in DRG cells was also suppressed.

Conclusion: These results suggested that SC-derived exosomes have a repairing effect on DRG cells injury caused by cyclic mechanical stretching (CMS) and the Wnt/β-catenin pathway is potentially involved in the process.
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http://dx.doi.org/10.1111/jog.14968DOI Listing
October 2021

High-Throughput Discovery of Novel Cubic Crystal Materials Using Deep Generative Neural Networks.

Adv Sci (Weinh) 2021 Aug 5:e2100566. Epub 2021 Aug 5.

Department of Computer Science and Engineering, University of South Carolina, Columbia, SC, 29201, USA.

High-throughput screening has become one of the major strategies for the discovery of novel functional materials. However, its effectiveness is severely limited by the lack of sufficient and diverse materials in current materials repositories such as the open quantum materials database (OQMD). Recent progress in deep learning have enabled generative strategies that learn implicit chemical rules for creating hypothetical materials with new compositions and structures. However, current materials generative models have difficulty in generating structurally diverse, chemically valid, and stable materials. Here we propose CubicGAN, a generative adversarial network (GAN) based deep neural network model for large scale generative design of novel cubic materials. When trained on 375 749 ternary materials from the OQMD database, the authors show that the model is able to not only rediscover most of the currently known cubic materials but also generate hypothetical materials of new structure prototypes. A total of 506 such materials have been verified by phonon dispersion calculation. Considering the importance of cubic materials in wide applications such as solar panels, the GAN model provides a promising approach to significantly expand existing materials repositories, enabling the discovery of new functional materials via screening. The new crystal structures discovered are freely accessible at www.carolinamatdb.org.
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http://dx.doi.org/10.1002/advs.202100566DOI Listing
August 2021

Neuronal cells from bipolar individuals are more susceptible to glutamate induced apoptosis than cells from non-bipolar subjects.

J Affect Disord 2021 Nov 20;294:568-573. Epub 2021 Jul 20.

Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, 401 East Chestnut Street, Suite 610, Louisville, KY 40202, USA. Electronic address:

Background: Bipolar disorder (BD) is associated with marked parenchymal brain loss in a significant fraction of patients. The lack of necrosis in postmortem examination suggests an apoptotic process. Emerging evidence suggests that mood stabilizers, like lithium, have antiapoptotic actions. Glutamatergic abnormalities have been associated with BD.

Methods: Olfactory neuroepithelial progenitors (ONPs) harvested by biopsy from type I bipolar patients (BD-ONPs, n = 3) and non-bipolar controls (non-BD-ONPs, n = 6), were treated with glutamate at concentrations sufficient to mimic the observed doubling of intracellular sodium known to occur in both mania and bipolar depression, to investigate potential differential lithium effect on both BD-ONPs and non-BD-ONPs.

Results: Apoptosis was detected in BP-ONPs exposed to 0.1 M glutamate for 6 h but in non-BD-ONPs at 24 h. Moreover, after treatment with 0.1 M glutamate treated for 6 h the levels of the pro-apoptotic cleaved-caspase-3 and cleaved-PARP proteins were significantly higher in BD-ONPs compare to non-BD-ONPs. Pretreatment with a therapeutic concentration of 1 mM lithium for 3 days attenuated the glutamate induced apoptosis. Lithium pretreatment 3 days also prevented the DNA fragmentation induced by glutamate, and significantly increased the antiapoptotic phospho-B-Raf and Bcl-2 proteins in BD-ONPs compared to non-BD-ONPs.

Limitations: ONPs are obtained from subjects with and without bipolar illness, but outcome of their study may still not reflect the biology of the illness.

Conclusions: ONPs derived from BD are more susceptible to glutamate-induced apoptosis. Lithium is associated with a greater increase of anti-apoptotic B-Raf and Bcl-2 expression in BD-ONPs.
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http://dx.doi.org/10.1016/j.jad.2021.07.064DOI Listing
November 2021
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