Publications by authors named "Dan Ma"

276 Publications

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes.

Mol Immunol 2021 Apr 12;135:36-44. Epub 2021 Apr 12.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, 030032, China. Electronic address:

Background: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX).

Methods: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-β expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).

Results: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-β expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA.

Conclusions: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.
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http://dx.doi.org/10.1016/j.molimm.2021.04.001DOI Listing
April 2021

Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis.

Lupus 2021 Apr 15:9612033211007199. Epub 2021 Apr 15.

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China.

Objectives: This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE.

Methods: A literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases' inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ- group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software.

Results: Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ- group (OR 0.35, 95% CI 0.21-0.59), (OR 0.41, 95% CI 0.19-0.89) and (OR 0.55, 95% CI 0.36-0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19-3.96), gestational diabetes (OR 2.3, 95% CI 0.44-12.12), thrombotic events (OR 0.26, 95% CI 0.05-1.51), spontaneous abortion (OR 1.77, 95% CI 0.96-3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24-1.39), oligohydramnios (OR 0.90, 95% CI 0.38-2.14), live birth (OR 1.22, 95% CI 0.60-2.47), stillbirth (OR 1.00, 95% CI 0.50-2.00), congenital malformation (OR 0.53, 95% CI 0.14-2.04), low birth weight (OR 0.77, 95% CI 0.43-1.39), intrauterine distress (OR 1.07, 95% CI 0.41-2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06-5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20-2.58) between the two groups.

Conclusions: HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.
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http://dx.doi.org/10.1177/09612033211007199DOI Listing
April 2021

Neighborhood Environment, Internet Use and Mental Distress among Older Adults: The Case of Shanghai, China.

Authors:
Dan Ma Hao Yuan

Int J Environ Res Public Health 2021 Mar 31;18(7). Epub 2021 Mar 31.

School of Sociology and Political Science, Shanghai University, Shanghai 200444, China.

As the Internet evolves in urban communities, its consequences on mental distress have drawn significant research attention. We examine the relationships of mental distress with neighborhood environment and Internet use among older adults, using data from a representative sample of 2036 adults aged older than 60 years in Shanghai, China. We assess mental health with a 10-item scale from the Symptom Checklist 90 and Internet use with a 4-item scale and obtain information of neighborhood environment from an online map platform. Results from multilevel models show that both neighborhood environment and Internet use are significantly related to mental distress. Moreover, a worse neighborhood environment may strengthen the correlation between Internet use and mental distress, indicating the strong moderating role of the neighborhood environment. Thus, promoting Internet use among elderly people might result in a reduction in the prevalence of mental distress in disadvantaged neighborhoods.
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http://dx.doi.org/10.3390/ijerph18073616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037533PMC
March 2021

Establishing Classification Tree Models in Rheumatoid Arthritis Using Combination of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Magnetic Beads.

Front Med (Lausanne) 2021 24;8:609773. Epub 2021 Feb 24.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

There is no simple method for early diagnosis and evaluation of rheumatoid arthritis (RA). This study aimed to determine potential biomarkers and establish diagnostic patterns for RA using proteomic fingerprint technology combined with magnetic beads. The serum protein profiles of 97 RA patients and 76 healthy controls (HCs) were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with weak cationic exchange (WCX) magnetic beads. Samples were randomly divided into training (83 RA patients and 56 HCs) and test sets (14 RA patients and 20 HCs). Patients were classified according to their Disease Activity Score: in remission, = 28; with low disease activity, = 17; with moderate disease activity, = 21; with high disease activity, = 31. There are 44 RA patients alone, 22 RA patients with interstitial lung disease (RA-ILD), 18 RA patients with secondary Sjögren's syndrome (RA-sSS), 6 RA patients with osteonecrosis of the femoral head (RA-ONFH), and 7 RA patients with other complications. Eleven patients were treated with etanercept only for half a year, after which their serum protein profiles were detected. The proteomic pattern was identified by Biomarker Patterns Software, and the potential biomarkers for RA diagnosis were further identified and quantified by enzyme-linked immunosorbent assay. The diagnostic pattern with four potential protein biomarkers, mass-to-charge (m/z) 3,448.85, 4,716.71, 8,214.29, and 10,645.10, could accurately recognize RA patients from HCs (specificity, 91.57%; sensitivity, 92.86%). The test set were correctly classified by this model (sensitivity, 95%; specificity, 100%). The components containing the four biomarkers were preliminarily retrieved through the ExPasy database, including the C-C motif chemokine 24 (CCL24), putative metallothionein (MT1DP), sarcolipin (SLN), and C-X-C motif chemokine 11 (CCXL11). Only the CCL24 level was detected to have a significant decrease in the serum of RA patients as compared with HCs ( < 0.05). No significant difference was found in others, but a decreasing trend consistent with the down-regulation of the four biomarkers detected by MALDI-TOF-MS was observed. The diagnostic models could effectively discriminate between RA alone and RA with complications (RA-ILD: m/z 10,645.10 and 12,595.86; RA-sSS: m/z 6,635.62 and 33,897.72; RA-ONFH: m/z 2,071.689). The classification model, including m/z 1,130.776, 1,501.065, 2,091.198, and 11,381.87, could distinguish between RA patients with disease activity and those in remission. RA with low disease activity could be efficiently discriminated from other disease activity patients by specific protein biomarkers (m/z 2,032.31, 2,506.214, and Z9286.495). Two biomarkers (m/z 2,032.31 and 4,716.71) were applied to build the classification model for RA patients with moderate and high disease activities. Biological markers for etanercept (m/z 2,671.604064, 5,801.840579, 8,130.195641, and 9,286.49499) were observed between the responder ( = 7) and non-responder groups ( = 4) ( < 0.05). We successfully established a series of diagnostic models involving RA and RA with complications as well as assessed disease activity. Furthermore, we found that CCL24 may be a valuable auxiliary diagnostic indicator for RA. These results provide reference values for clinical practice in the future.
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http://dx.doi.org/10.3389/fmed.2021.609773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943484PMC
February 2021

Correlation between the elevated uric acid levels and circulating renin-angiotensin-aldosterone system activation in patients with atrial fibrillation.

Cardiovasc Diagn Ther 2021 Feb;11(1):50-55

Coronary Care Unit, Beijing Hepingli Hospital, Beijing, China.

Background: The aim of the present study was to investigate the correlation between the elevated uric acid (UA) levels and activation of the circulating renin-angiotensin-aldosterone system (RAAS) in patients with atrial fibrillation (AF).

Methods: A total of 233 outpatients and inpatients of the Cardiology Department from January 1, 2019, to December 31, 2019, were selected and divided into the sinus rhythm group (SR) with 84 cases, the paroxysmal AF group (pAF) with 76 cases, and the persistent AF group (PAF) with 73 patients. The general clinical data and the serum levels of UA of the enrolled patients were collected, and the radioimmunoassay was adopted to detect the levels of renin (Renin), angiotensin II (Ang II), and aldosterone (Ald).

Results: Renin, AngII, Ald, and UA in the PAF group were significantly higher than those in the pAF group, and the levels of the above indicators in the pAF group were significantly higher than those in the SR group (P<0.001). The left atrium anteroposterior diameter (LAD) and the left ventricular end-diastolic diameter (LVEDD) were significantly increased in the PAF group (P<0.001). The Pearson correlation analysis showed that the levels of the high sensitivity C-reactive protein (hsCRP), AngII Renin, Ald, LVEDD, and LAD were positively correlated with the serum levels of UA (r=0.174, 0.273, 0.34, 0.385, 0.138, respectively, P<0.05 in all). The left ventricular ejection fraction (LVEF) was negatively correlated with the UA level (r=-0.177, P<0.05). Multiple linear regression analysis showed that UA (β=0.103) and LAD (β=2.162) were independent risk factors for Renin. The independent risk factor for Ang II was UA (β=0.167). The independent risk factor for Ald was UA (β=0.283) and LAD (β=8.721) (P<0.05).

Conclusions: Elevated UA might cause excessive activation of the RAAS, aggravate the oxidative stress, and participate in the atrial remodeling, thereby promoting the occurrence and persistence of AF.
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http://dx.doi.org/10.21037/cdt-20-830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944194PMC
February 2021

Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis.

Biosci Rep 2021 Mar 1. Epub 2021 Mar 1.

Tianjin Medical University General Hospital, Tianjin, China.

Cervical cancer is one of the most diagnosed malignancies among females. The 5-fluorouracil (5-Fu) is a widely used chemotherapeutic agent against diverse cancers. Despite the initially encouraging progresses, a fraction of cervical cancer patients developed 5-Fu resistance. We detected that NEAT1 was significantly upregulated in cervical cancer tissues and cell lines. Moreover, NEAT1 was positively associated with 5-Fu resistance. Furthermore, expression of NEAT1 was significantly upregulated in 5-Fu resistant CaSki cervical cancer cells. Knocking down NEAT1 by shRNA dramatically promoted the sensitivity of 5-Fu resistant CaSki cells. We observed a negative correlation between lncRNA-NEAT1 and miR-34a in cervical cancer patient tissues. Overexpression of miR-34a significantly sensitized 5-Fu resistant cells. Bioinformatical analysis uncovered that NEAT1 functions as a competitive endogenous RNA (ceRNA) of miR-34a in cervical cancer cells via sponging it at multiple sites to suppress expression of miR-34a. This negative association between NEAT1 and miR-34a was further verified in cervical cancer tissues. We found the 5-Fu resistant cells displayed significantly increased glycolysis rate. Overexpression of miR-34a suppressed cellular glycolysis rate and sensitized 5-Fu resistant cells through direct targeting the 3'UTR of LDHA, a glycolysis key enzyme. Importantly, knocking down NEAT1 successfully downregulated LDHA expressions and glycolysis rate of cervical cancer cells by upregulating miR-34a, a process could be further rescued by miR-34a inhibition. Finally, we demonstrated inhibition of NEAT1 significantly sensitized cervical cancer cells to 5-Fu through the miR-34a/LDHA pathway. In summary, this study suggests a new molecular mechanism for the NEAT1-mediated 5-Fu resistance via the miR-34a/LDHA-glycolysis axis.
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http://dx.doi.org/10.1042/BSR20200533DOI Listing
March 2021

Inhibition of PDE1-B by Vinpocetine Regulates Microglial Exosomes and Polarization Through Enhancing Autophagic Flux for Neuroprotection Against Ischemic Stroke.

Front Cell Dev Biol 2020 4;8:616590. Epub 2021 Feb 4.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou, China.

Exosomes contribute to cell-cell communications. Emerging evidence has shown that microglial exosomes may play crucial role in regulation of neuronal functions under ischemic conditions. However, the underlying mechanisms of microglia-derived exosome biosynthesis are largely unknown. Herein, we reported that the microglial PDE1-B expression was progressively elevated in the peri-infarct region after focal middle cerebral artery occlusion. By an oxygen-glucose-deprivation (OGD) ischemic model in cells, we found that inhibition of PDE1-B by vinpocetine in the microglial cells promoted M2 and inhibited M1 phenotype. In addition, knockdown or inhibition of PDE1-B significantly enhanced the autophagic flux in BV2 cells, and vinpocetine-mediated suppression of M1 phenotype was dependent on autophagy in ischemic conditions. Co-culture of BV2 cells and neurons revealed that vinpocetine-treated BV2 cells alleviated OGD-induced neuronal damage, and treatment of BV2 cells with 3-MA abolished the observed effects of vinpocetine. We further demonstrated that ischemia and vinpocetine treatment significantly altered microglial exosome biogenesis and release, which could be taken up by recipient neurons and regulated neuronal damage. Finally, we showed that the isolated exosome from conditioned BV2 cells is sufficient to regulate cortical neuronal survival . Taken together, these results revealed a novel microglia-neuron interaction mediated by microglia-derived exosomes under ischemic conditions. Our findings further suggest that PDE1-B regulates autophagic flux and exosome biogenesis in microglia which plays a crucial role in neuronal survival under cerebral ischemic conditions.
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http://dx.doi.org/10.3389/fcell.2020.616590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889976PMC
February 2021

PKC-β/Alox5 axis activation promotes Bcr-Abl-independent TKI-resistance in chronic myeloid leukemia.

J Cell Physiol 2021 Feb 9. Epub 2021 Feb 9.

Department of Hematology, Key Laboratory of Hematological Disease Diagnostic & Treat Center of Guizhou Province, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Bcr-Abl independent resistance to tyrosine kinase inhibitor (TKI) is a crucial factor lead to relapse or acute leukemia transformation in chronic myeloid leukemia (CML). However, its mechanism is still unclear. Herein, we found that of nine common protein kinases C (PKCs), PKC-β overexpression was significantly related with TKI resistance. Blockage of its expression in CD34+ cells and CML cell lines increased sensitivity to imatinib. Then, eighty-four leukemia related genes were compared between TKI-resistant CML cell lines with PKC-β silenced or not. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that Arachidonate 5-lipoxygenase (Alox5) and its relative pathway mainly participated in the resistance induced by PKC-β overexpression. It's also observed that Alox5 was increased not only in bone marrow biopsy but also in CD34 cells derived from IM-resistant CML patients. The signaling pathway exploration indicated that ERK1/2 pathway mediates Alox5 upregulation by PKC-β. Meanwhile, we also proved that Alox5 induces TKI-insensitivity in CML through inactivation of PTEN. In vivo experiment, PKC-β elective inhibitor LY333531 prolonged survival time in CML-PDX mice model. In conclusion, targeted on PKC-β overexpression might be a novel therapy mechanism to overcome TKI-resistance in CML.
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http://dx.doi.org/10.1002/jcp.30301DOI Listing
February 2021

Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes.

Int Immunopharmacol 2021 Apr 30;93:107392. Epub 2021 Jan 30.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, PR China. Electronic address:

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects synovial joints. During the course of RA, the synovium transforms into hyperplastic invasive tissue, leading to cartilage and bone destruction. Fibroblast-like synoviocytes (FLS) in the synovial lining develop aggressive phenotypes and produce pathogenic mediators that lead to the occurrence and progression of disease, playing a major role in RA pathophysiology. Therefore, research on FLS has become the main focus within the RA field. With technical advances and the development of multi-omics comprehensive analysis approaches, it has become possible to identify different FLS subsets via high-throughput sequencing and investigate differences between FLS phenotypes, allowing for the detailed study of RA pathogenesis. This review summarizes recent works on FLS subtypes and the surface marker proteins identified for different subtypes, providing a theoretical basis and reference for future studies on FLS in RA. The current work also addresses the clinical potential of FLS surface markers in RA based on related research from other fields.
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http://dx.doi.org/10.1016/j.intimp.2021.107392DOI Listing
April 2021

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Chin Med J (Engl) 2021 Feb 1. Epub 2021 Feb 1.

Department of Rheumatology, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, China Department of Rheumatology, Shanxi Bethune Hospital, Taiyuan, Shanxi 030032, China.

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http://dx.doi.org/10.1097/CM9.0000000000001374DOI Listing
February 2021

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Chin Med J (Engl) 2021 Feb 1. Epub 2021 Feb 1.

Department of Rheumatology, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, China Department of Rheumatology, Shanxi Bethune Hospital, Taiyuan, Shanxi 030032, China.

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http://dx.doi.org/10.1097/CM9.0000000000001374DOI Listing
February 2021

Nrf2 overexpression increases risk of high tumor mutation burden in acute myeloid leukemia by inhibiting MSH2.

Cell Death Dis 2021 Jan 5;12(1):20. Epub 2021 Jan 5.

Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, 550004, Guiyang, China.

Nuclear factor erythroid 2-related factor 2 (Nrf2, also called NFE2L2) plays an important role in cancer chemoresistance. However, little is known about the role of Nrf2 in tumor mutation burden and the effect of Nrf2 in modulating DNA mismatch repair (MMR) gene in acute myeloid leukemia (AML). Here we show that Nrf2 expression is associated with tumor mutation burden in AML. Patients with Nrf2 overexpression had a higher frequency of gene mutation and drug resistance. Nrf2 overexpression protected the AML cells from apoptosis induced by cytarabine in vitro and increased the risk of drug resistance associated with a gene mutation in vivo. Furthermore, Nrf2 overexpression inhibited MutS Homolog 2 (MSH2) protein expression, which caused DNA MMR deficiency. Mechanistically, the inhibition of MSH2 by Nrf2 was in a ROS-independent manner. Further studies showed that an increased activation of JNK/c-Jun signaling in Nrf2 overexpression cells inhibited the expression of the MSH2 protein. Our findings provide evidence that high Nrf2 expression can induce gene instability-dependent drug resistance in AML. This study demonstrates the reason why the high Nrf2 expression leads to the increase of gene mutation frequency in AML, and provides a new strategy for clinical practice.
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http://dx.doi.org/10.1038/s41419-020-03331-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790830PMC
January 2021

The effects of the recombinant YeaZ of on the resuscitation and growth of soil bacteria in extreme soil environment.

PeerJ 2020 21;8:e10342. Epub 2020 Dec 21.

School of Petrochemical Engineering, Lanzhou University of Technology, Lanzhou, China.

Numerous bacteria entered the viable but non-culturable state due to the stresses of dry and salt in soils. YeaZ of Gram-negative bacteria is a resuscitation promoting factor (Rpf) homologous protein could resuscitate bacteria of natural environment in VBNC state. To investigate the promoting effect of YeaZ on the isolation of viable but non-culturable (VBNC) bacteria from soil samples in extreme environments, the recombinant YeaZ of was prepared and added to the soil samples from volcanic soil and saline soil in Northwest China. The study has shown that YeaZ can promote the recovery and growth of soil microorganisms, and the number of cultivable bacteria in volcanic and saline soil has increased from 0.17 × 10 and 2.03 × 10 cfu⋅ml to 1.00 × 10 and 5.55 × 10 cfu⋅ml, respectively. The 16S rDNA gene sequencing and phylogenetic analysis showed that YeaZ played an essential role in the increase of composition and diversity of bacteria. A total of 13 bacterial strains were isolated from the volcanic soil samples, which belong to phyla Actinobacteria, Firmicutes and Gamma-proteobacteria. Four species, including , , and were found in the control group, while , , , , and were isolated from the treatment groups (addition of YeaZ). Twenty-one strains were isolated from the saline soil samples, including eight species from the control group and thirteen species from the treatment groups, among which nine species were only found, including , , , , , , , and . The results suggest that addition of YeaZ to soil samples can promote the recovery of VBNC. This method has the implications for the discovery of VBNC bacteria that have potential environmental functions.
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http://dx.doi.org/10.7717/peerj.10342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759134PMC
December 2020

targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer.

Gut 2020 Dec 14. Epub 2020 Dec 14.

State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Objective: Microbiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.

Design: F-FDG (F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in -induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.

Results: We have found . abundance correlated with high glucose metabolism in patients with CRC. Furthermore, supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.

Conclusion: and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated .
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http://dx.doi.org/10.1136/gutjnl-2020-322780DOI Listing
December 2020

Clonal expansion of bone marrow CD8 T cells in acute myeloid leukemia patients at new diagnosis and after chemotherapy.

Am J Cancer Res 2020 1;10(11):3973-3989. Epub 2020 Nov 1.

Department of Clinical Medical School, Guizhou Medical University Guiyang, Guizhou, China.

CD8 T cells are crucial adaptive immune effectors and express receptors (T cell receptors, TCRs) that specifically recognize and eradicate tumor cells. The diversity of the TCR repertoire is generated by specialized genetic diversification mechanisms, which lead to an extremely variable TCR repertoire that is capable of recognizing a wide range of antigens. However, the variations in CD8 TCR diversity and their clinical implications in acute myeloid leukemia (AML) patients remain unknown. CD8 T cells were enriched from 10 healthy donors and 31 AML patients at diagnosis and after chemotherapy, and TCRβ deep sequencing was performed to analyze CD8 T cell clonal expansion and TCR repertoire diversity. Diminished TCR repertoire diversity and increased T cell clone expansion were noted in the bone marrow of AML patients. In relapsed patients, T cells were found to be more clonally expanded after chemotherapy than at new diagnosis. Moreover, significantly more expanded TCRβ clonotypes were noted in CD8 PD-1 T cells than in CD8 PD-1 T cells regardless of the time of examination. Our systematic T cell repertoire analysis may help better characterize CD8 T cells before and after chemotherapy in AML, which may provide insights into therapeutic strategies for hematological malignancies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716150PMC
November 2020

Glucocorticoid resistance induced by ANXA5 overexpression in B-cell acute lymphoblastic leukemia.

Pediatr Hematol Oncol 2021 Feb 24;38(1):36-48. Epub 2020 Nov 24.

Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Development of chemo‑resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.
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http://dx.doi.org/10.1080/08880018.2020.1810182DOI Listing
February 2021

3D magnetic resonance fingerprinting with quadratic RF phase.

Magn Reson Med 2021 04 12;85(4):2084-2094. Epub 2020 Nov 12.

Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA.

Purpose: To implement 3D magnetic resonance fingerprinting (MRF) with quadratic RF phase (qRF-MRF) for simultaneous quantification of T , T , ΔB , and .

Methods: 3D MRF data with effective undersampling factor of 3 in the slice direction were acquired with quadratic RF phase patterns for T , T , and sensitivity. Quadratic RF phase encodes the off-resonance by modulating the on-resonance frequency linearly in time. Transition to 3D brings practical limitations for reconstruction and dictionary matching because of increased data and dictionary sizes. Randomized singular value decomposition (rSVD)-based compression in time and reduction in dictionary size with a quadratic interpolation method are combined to be able to process prohibitively large data sets in feasible reconstruction and matching times.

Results: Accuracy of 3D qRF-MRF maps in various resolutions and orientations are compared to 3D fast imaging with steady-state precession (FISP) for T and T contrast and to 2D qRF-MRF for contrast and ΔB . The precision of 3D qRF-MRF was 1.5-2 times higher than routine clinical scans. 3D qRF-MRF ΔB maps were further processed to highlight the susceptibility contrast.

Conclusion: Natively co-registered 3D whole brain T , T , , ΔB , and QSM maps can be acquired in as short as 5 min with 3D qRF-MRF.
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http://dx.doi.org/10.1002/mrm.28581DOI Listing
April 2021

Rapid MR relaxometry using deep learning: An overview of current techniques and emerging trends.

NMR Biomed 2020 Oct 15:e4416. Epub 2020 Oct 15.

Department of Radiology, Massachusetts General Hospital, Harvard University, Boston, Massachusetts.

Quantitative mapping of MR tissue parameters such as the spin-lattice relaxation time (T ), the spin-spin relaxation time (T ), and the spin-lattice relaxation in the rotating frame (T ), referred to as MR relaxometry in general, has demonstrated improved assessment in a wide range of clinical applications. Compared with conventional contrast-weighted (eg T -, T -, or T -weighted) MRI, MR relaxometry provides increased sensitivity to pathologies and delivers important information that can be more specific to tissue composition and microenvironment. The rise of deep learning in the past several years has been revolutionizing many aspects of MRI research, including image reconstruction, image analysis, and disease diagnosis and prognosis. Although deep learning has also shown great potential for MR relaxometry and quantitative MRI in general, this research direction has been much less explored to date. The goal of this paper is to discuss the applications of deep learning for rapid MR relaxometry and to review emerging deep-learning-based techniques that can be applied to improve MR relaxometry in terms of imaging speed, image quality, and quantification robustness. The paper is comprised of an introduction and four more sections. Section 2 describes a summary of the imaging models of quantitative MR relaxometry. In Section 3, we review existing "classical" methods for accelerating MR relaxometry, including state-of-the-art spatiotemporal acceleration techniques, model-based reconstruction methods, and efficient parameter generation approaches. Section 4 then presents how deep learning can be used to improve MR relaxometry and how it is linked to conventional techniques. The final section concludes the review by discussing the promise and existing challenges of deep learning for rapid MR relaxometry and potential solutions to address these challenges.
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http://dx.doi.org/10.1002/nbm.4416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046845PMC
October 2020

Reutilization of gangue wastes in underground backfilling mining: Overburden aquifer protection.

Chemosphere 2021 Feb 24;264(Pt 1):128400. Epub 2020 Sep 24.

State Key Laboratory of Coal Resources and Safe Mining, School of Mines, China University of Mining & Technology, Xuzhou, 221116, Jiangsu, China; Key Laboratory of Deep Coal Resource Mining of Ministry of Education, China University of Mining & Technology, Xuzhou, 221116, Jiangsu, China.

Gangue backfilling mining (GBM) can effectively alleviate the gangue accumulation pollution and the overburden aquifer destruction. To efficiently evaluate the reutilization of gangue wastes by GBM and its advantage in overburden aquifer protection, non-Darcy hydraulic properties and deformation behaviors of granular gangues were studied through laboratorial, theoretical, and in-situ aspects. A series of compression and seepage tests on granular gangues under the variable original grain size grade (GSG) and stress rate were conducted. Laboratorial testing results convince that, hydraulic properties (porosity and permeability) of the granular gangue decline with the increasing original GSG and decreasing stress rate. The crushing ratio of the sample increases with the increase of original GSG and the decrease of stress rate. The fractal dimension reveals more obvious increases in the samples with the higher original GSGs and lower stress rates. The Kruger model (a classical theoretical model) was employed to predict the permeability evolution based on the porosity. However, the invalid pores in rocks would result in the model's underestimation. To this end, an improved model was established to predict the permeability evolution by the fractal dimension, and the improved Kruger model has better accuracy than the original one. Finally, according to the laboratorial testing and theoretical predicted results, friendly-environmental strategies for overburden aquifer protection were proposed. The effectiveness of these strategies was successfully verified by an in-situ application. It is concluded that the high filling stress, low gangue original GSG, and low filling stress rate in GBM can effectively reduce the risk of overburden aquifer destruction.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128400DOI Listing
February 2021

Radiomic analysis of magnetic resonance fingerprinting in adult brain tumors.

Eur J Nucl Med Mol Imaging 2021 Mar 26;48(3):683-693. Epub 2020 Sep 26.

Department of Radiology, Case Western Reserve University and University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH, 44106, USA.

Purpose: This is a radiomics study investigating the ability of texture analysis of MRF maps to improve differentiation between intra-axial adult brain tumors and to predict survival in the glioblastoma cohort.

Methods: Magnetic resonance fingerprinting (MRF) acquisition was performed on 31 patients across 3 groups: 17 glioblastomas, 6 low-grade gliomas, and 8 metastases. Using regions of interest for the solid tumor and peritumoral white matter on T1 and T2 maps, second-order texture features were calculated from gray-level co-occurrence matrices and gray-level run length matrices. Selected features were compared across the three tumor groups using Wilcoxon rank-sum test. Receiver operating characteristic curve analysis was performed for each feature. Kaplan-Meier method was used for survival analysis with log rank tests.

Results: Low-grade gliomas and glioblastomas had significantly higher run percentage, run entropy, and information measure of correlation 1 on T1 than metastases (p < 0.017). The best separation of all three tumor types was seen utilizing inverse difference normalized and homogeneity values for peritumoral white matter in both T1 and T2 maps (p < 0.017). In solid tumor T2 maps, lower values in entropy and higher values of maximum probability and high-gray run emphasis were associated with longer survival in glioblastoma patients (p < 0.05). Several texture features were associated with longer survival in glioblastoma patients on peritumoral white matter T1 maps (p < 0.05).

Conclusion: Texture analysis of MRF-derived maps can improve our ability to differentiate common adult brain tumors by characterizing tumor heterogeneity, and may have a role in predicting outcomes in patients with glioblastoma.
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http://dx.doi.org/10.1007/s00259-020-05037-wDOI Listing
March 2021

[Application and Progress of Real-time Interleaved Transcranial Magnetic Stimulation Functional Magnetic Resonance Imaging].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 Sep;51(5):592-598

Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China.

Transcranial magnetic stimulation (TMS), as a non-invasive neuromodulation technique, has achieved certain results in the study of brain function localization, treatment of nervous and mental diseases, but its mechanism of action and physiological effects are difficult to be clarified. The signals in blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is capable of reflecting the activities of brain tissue neurons. TMS-fMRI combines the advantages of two techniques to monitor changes in excitability of the TMS stimulation site and the distal brain region with which it is functionally linked. In this review, we elaborates the advances, limitations and future expectations of real-time interleaved TMS-fMRI. From the perspective of application progress, in the field of brain functional connectivity network research, TMS-fMRI can observe the dynamic connection between brain networks with a resolution of 100 ms, which is an important progress in the exploration of time-specific functional connectivity of brain regions. However, the TMS-fMRI on spatial specificity of functional connectivity of brain regions is still unclear, and future studies can focus on this aspect. In addition, TMS-fMRI can assess the effect of TMS on the cerebral cortex and the interaction between brain regions, help us understand the neural mechanism behind attention control, and study the brain's processing of somatosensory sensation. Nevertheless, TMS-fMRI can only observe the correlation between excitability of different brain regions under the stimulation of TMS, but the mechanism of this phenomenon and whether the correlation between brain regions is specific needs more research. Futhermore, TMS-fMRI can also be used to study the pathogenesis and therapeutic effect of neurological and psychiatric diseases, and the effects of psychoactive compounds on brain regions. Nonetheless, currently TMS-fMRI is still difficult to be widely used in clinical practice, so more efforts are needed in the study of clinical indications of TMS-fMRI. There are two major technical problems of TMS-fMRI. One major problem is that it is difficult for TMS coils to accurately position specific areas of cerebral cortex in MRI scanner. Another major problem is that TMS coils affect the static magnetic field (B0), resulting in image artifacts, spatial distortion and local signal loss of echo-Planar (EP) images. Nowadays, researchers have solved the two major problems through continuous technical updates, but TMS-fMRI still has problems in parameter setting, user experience, simplicity and universality of application and other aspects, which is the direction of future technological progress.
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http://dx.doi.org/10.12182/20200960202DOI Listing
September 2020

Human papillomavirus oropharynx carcinoma: Aggressive de-escalation of adjuvant therapy.

Head Neck 2021 Jan 23;43(1):229-237. Epub 2020 Sep 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Aggressive dose de-escalated adjuvant radiation therapy (RT) in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).

Methods: Patients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de-escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence-free, regional recurrence-free, distant metastases-free survival, and progression-free survival (PFS) were assessed.

Results: Of 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7-2.0; range 0.3-5.4); 10 patients in the de-escalated cohort and 13 patients in the standard cohort. The 3-year PFS rate for the de-escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50-2.75]).

Conclusion: Patients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de-escalation of RT without increasing risk of progression locally, regionally or at distant sites.
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http://dx.doi.org/10.1002/hed.26477DOI Listing
January 2021

HDAC3 Silencing Enhances Acute B Lymphoblastic Leukaemia Cells Sensitivity to MG-132 by Inhibiting the JAK/Signal Transducer and Activator of Transcription 3 Signaling Pathway.

Chemotherapy 2020 23;65(3-4):85-100. Epub 2020 Sep 23.

Key Laboratory of Hematological Disease Diagnostic Treat Centre of Guizhou Province, Guiyang, China,

Purpose: HDAC3, which is associated with smurf2, has been shown to be associated with poor prognosis in B-ALL. This study examined the efficacy of targeting HDAC3 combined with MG-132 as a possible therapeutic strategy for B-ALL patients.

Methods: Real-time PCR and western blot were used to measure the expression of smurf2 and HDAC3 from B-ALL patients bone marrow samples. Sup-B15 and CCRF-SB cells were treated with MG-132, small interfering RNA of smurf2 or HDAC3. A plasmid designed to up-regulate smurf2 expression was transfected into B-ALL cells. Flow cytometry and western blot were used to measure variation due to these treatments in terms of apoptosis and cell cycle arrest.

Results: Expression of Smurf2 and HDAC3 mRNA were inversely related in B-ALL patients. Up-regulation of smurf2 or MG-132 influenced HDAC3, further inhibiting the JAK/signal transducer and activator of transcription 3 (STAT3) signal pathway and inducing apoptosis in B-ALL cells. When we treated Sup-B15 and CCRF-SB cells with siHDAC3 and MG-132 for 24 h, silencing HDAC3 enhanced the apoptosis rate induced by MG-132 in B-ALL cells and further inhibited the JAK/STAT3 pathway. Furthermore, MG-132 was observed to cause G2/M phase arrest in B-ALL cells and inhibited the JAK/STAT3 pathway, leading to apoptosis.

Conclusions: Silencing of HDAC3 enhanced the sensitivity of B-ALL cells to MG-132. The combination of targeting HDAC3 and MG-132 may provide a new avenue for clinical treatment of acute B lymphocytic leukaemia and improve the poor survival of leukaemia patients.
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http://dx.doi.org/10.1159/000500713DOI Listing
September 2020

Application of single-cell sequencing in autoimmune diseases.

Chin Med J (Engl) 2020 Sep 1;134(4):495-497. Epub 2020 Sep 1.

Department of Rheumatology, Shanxi Bethune Hospital, Taiyuan, Shanxi 030032, China.

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http://dx.doi.org/10.1097/CM9.0000000000001050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909166PMC
September 2020

Computational design of transmembrane pores.

Nature 2020 09 26;585(7823):129-134. Epub 2020 Aug 26.

Institute for Protein Design, University of Washington, Seattle, WA, USA.

Transmembrane channels and pores have key roles in fundamental biological processes and in biotechnological applications such as DNA nanopore sequencing, resulting in considerable interest in the design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels, and there have been recent advances in de novo membrane protein design and in redesigning naturally occurring channel-containing proteins. However, the de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores remains an outstanding challenge. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments show that, when expressed in insect cells, the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modification at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications.
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http://dx.doi.org/10.1038/s41586-020-2646-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483984PMC
September 2020

Structural basis for diamide modulation of ryanodine receptor.

Nat Chem Biol 2020 11 17;16(11):1246-1254. Epub 2020 Aug 17.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous assignment of the CHL binding site. The molecule induces a conformational change by affecting the S4-S5 linker, triggering channel opening. The binding site is further corroborated by mutagenesis data, which reveal how diamide insecticides are selective to the Lepidoptera group of insects over honeybee or mammalian RyRs. Our data reveal that several pests have developed resistance via two mechanisms, steric hindrance and loss of contact. Our results provide a foundation for the development of highly selective pesticides aimed at overcoming resistance and therapeutic molecules to treat human myopathies.
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http://dx.doi.org/10.1038/s41589-020-0627-5DOI Listing
November 2020

Preclinical Assessment of the Effectiveness of Magnetic Resonance Molecular Imaging of Extradomain-B Fibronectin for Detection and Characterization of Oral Cancer.

Mol Imaging Biol 2020 12 12;22(6):1532-1542. Epub 2020 Aug 12.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.

Purpose: Oral squamous cell carcinoma (OSCC) has not seen a substantial improvement in patient survival despite therapeutic advances, making accurate detection and characterization of the disease a clinical priority. Here, we aim to demonstrate the effectiveness of magnetic resonance imaging (MRI) with the targeted MRI contrast agent MT218 specific to extradomain-B fibronectin (EDB-FN) in the tumor microenvironment for detection and characterization of aggressive OSCC tumors.

Procedures: EDB-FN expression was evaluated in human normal tongue and OSCC specimens with immunohistochemistry. Invasiveness of human CAL27, HSC3, and SCC4 OSCC cells was analyzed with spheroid formation and transwell assays. EDB-FN expression in the cells was analyzed with semiquantitative real-time PCR, western blotting, and a peptide binding study with confocal microscopy. Contrast-enhanced MRI with MT218 was performed on subcutaneous OSCC mouse models at a dose of 0.04 mmol/kg, using gadoteridol (0.1 mmol/kg) as a control.

Results: Strong EDB-FN expression was observed in human untreated primary and metastatic OSCC, reduced expression in treated OSCC, and little expression in normal tongue tissue. SCC4 and HSC3 cell lines demonstrated high invasive potential with high and moderate-EDB-FN expression, respectively, while CAL27 showed little invasive potential and low-EDB-FN expression. In T-weighted MRI, MT218 produced differential contrast enhancement in the subcutaneous tumor models in correlation with EDB-FN expression in the cancer cells. Enhancement in the high-EDB-FN tumors was greater with MT218 at 0.04 mmol/kg than gadoteridol at 0.1 mmol/kg.

Conclusions: The results suggest EDB-FN has strong potential as an imageable biomarker for aggressive OSCC. MRMI results demonstrate the effectiveness of MT218 and the potential for differential diagnostic imaging of oral cancer for improving the management of the disease.
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http://dx.doi.org/10.1007/s11307-020-01524-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669711PMC
December 2020

Prediction of water inflow from fault by particle swarm optimization-based modified grey models.

Environ Sci Pollut Res Int 2020 Nov 23;27(33):42051-42063. Epub 2020 Jul 23.

School of Resources & Safety Engineering, Central South University, Changsha, 410083, Hunan, China.

Water inflow from fault (WIF) and its secondary impacts are the main environmental challenges in the mining industry. Traditional prediction methods for WIF are exceedingly challenging and costly. In this article, two exponentially weighted moving average (EWMA) modified grey models (GMs, i.e., EGM and REGM) were established to predict the WIF. Particle swarm optimization (PSO) algorithm was employed to optimize parameters of the models. Based on actual WIF data from Buliangou coal mine, the optimized models (i.e., EGM-PSO, REGM-PSO) were used to obtain the prediction equations for WIF. To investigate the validity of the proposed models, the differences between actual values and predicted values were analyzed, and comparison results were obtained by the commonly used GM and GM-PSO. Results show that, for the sample with the larger initial particle swarm and smaller inertia weight, there is a faster convergence speed of the PSO algorithm. Particle search efficiency in the PSO-optimized EWMA-GM is higher than that in the GM-PSO. Through the predicted results of WIF, it is found that the REGM-PSO is the best choice for WIF prediction, and the more historical information, the higher the predicted accuracy. Besides, the parameter optimization by the PSO, the EWMA optimization method and optimization of residuals all can improve the predicted accuracy. Predicted results also show that WIF will have a substantial growth in the future. Therefore, reasonable measures (e.g., draining and grouting) need to be taken to mitigate the damage caused by fault water inflow.
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http://dx.doi.org/10.1007/s11356-020-10172-wDOI Listing
November 2020

4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism.

Am J Transl Res 2020 15;12(6):2968-2983. Epub 2020 Jun 15.

Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University Guiyang, P. R. China.

Epigenetic modifications play crucial roles in regulating the self-renewal and differentiation of hematopoiesis. 4SC-202, a novel inhibitor of histone lysine-specific demethylase 1 (LSD1) and class I histone deacetylases (HDACs), is a potential therapeutic agent to treat myelodysplastic syndrome (MDS). However, it remains unclarified of the mechanism of 4SC-202. In the study, we found that 4SC-202 treatment could inhibit cell viability, induce apoptosis and cause G2/M cell cycle arrest in MDS cell line SKM-1. Heme oxygenase-1 (HO-1) was correlated with disease progression and chemotherapy resistance. Here, we reported that 4SC-202 could down-regulate the expression of HO-1, and up-regulation of HO-1 could significantly attenuate the 4SC-202-induced apoptosis in SKM-1 cells. In addition, the activation of NF-κB pathway was suppressed by 4SC-202, while up-regulation of HO-1 significantly weakened the 4SC-202-induced suppression of the NF-κB pathway, thereby attenuating the efficacy of 4SC-202. However, down-regulation of HO-1 enhanced the sensitivity of 4SC-202 against SKM-1 cells. Moreover, SKM-1 cells were transfected with HO-1 overexpression lentivirus, subsequently injected into the tail vein of NOD/SCID mice, followed by administration of 4SC-202 in mice. As a result, up-regulation HO-1 could partially attenuate 4SC-202-suppressed MDS cells growth in NOD/SCID mice. In conclusion, 4SC-202 could induce apoptosis via the NF-κB pathway, and our present finding may provide a novel therapeutic strategy for MDS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344078PMC
June 2020