Publications by authors named "Fang Du"

259 Publications

Depletion of high-content CD14 cells from apheresis products is critical for successful transduction and expansion of CAR T cells during large-scale cGMP manufacturing.

Mol Ther Methods Clin Dev 2021 Sep 16;22:377-387. Epub 2021 Jul 16.

Michael G. Harris Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

With the US Food and Drug Administration (FDA) approval of four CD19- and one BCMA-targeted chimeric antigen receptor (CAR) therapy for B cell malignancies, CAR T cell therapy has finally reached the status of a medicinal product. The successful manufacturing of autologous CAR T cell products is a key requirement for this promising treatment modality. By analyzing the composition of 214 apheresis products from 210 subjects across eight disease indications, we found that high CD14 cell content poses a challenge for manufacturing CAR T cells, especially in patients with non-Hodgkin's lymphoma and multiple myeloma caused by the non-specific phagocytosis of the magnetic beads used to activate CD3 T cells. We demonstrated that monocyte depletion via rapid plastic surface adhesion significantly reduces the CD14 monocyte content in the apheresis products and simultaneously boosts the CD3 content. We established a 40% CD14 threshold for the stratification of apheresis products across nine clinical trials and demonstrated the effectiveness of this procedure by comparing manufacturing runs in two phase 1 clinical trials. Our study suggests that CD14 content should be monitored in apheresis products, and that the manufacturing of CAR T cells should incorporate a step that lessens the CD14 cell content in apheresis products containing more than 40% to maximize the production success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtm.2021.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411225PMC
September 2021

Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study).

Trials 2021 Aug 11;22(1):530. Epub 2021 Aug 11.

Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200001, China.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up.

Methods/design: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test.

Discussion: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients.

Trial Registration: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05475-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356213PMC
August 2021

Leaf morphological characteristics of section based on geometric morphometric analysis.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2309-2315

School of Ecology and Nature Conservation, Beijing Forestry University, Beijing 100083, China.

We conducted leaf geometric morphometric analysis (GMMs) for five species (Section ) of Fagaceae. In total, 887 leaves chosen from 182 individuals of 20 natural popu-lations were marked with GMMs. Leaf morphological characteristics of these samples were digitized to visualize leaf morphological differences. Generalized Procrustes analysis could effectively exclude the influence of leaf position and size on leaf shape. Results of principal component analysis at tree-level showed that the leaf morphology of was different with and . Canonical variates analysis at tree-level showed that leaf morphology of could be accurately distinguished from the other four species in leaf symmetric components. The results of multivariate analysis of asymmetrical components in leaves showed no distinction among the five species. The analysis at leaf-level showed that the two groups with a higher degree of discrimination were vs. (99.5% vs. 100%) and vs. (99.0% vs. 100%), which could be accurately distinguished by leaf shape. The two groups with a slightly lower degree of discrimination were vs. (90.5% vs. 86.8%) and vs. (85.1% vs. 82.9%). Our results provided new insights for the leaf shape identification among species with frequent hybridization and introgression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13287/j.1001-9332.202107.001DOI Listing
July 2021

Status Epilepticus in Patients with Anti-NMDAR Encephalitis Requiring Intensive Care: A Follow-Up Study.

Neurocrit Care 2021 Jul 20. Epub 2021 Jul 20.

Department of Neurology, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi Province, China.

Background: To date, specialized studies focusing on status epilepticus (SE) in anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis are limited, and the association between the occurrence of SE and clinical outcome is controversial. This study aims to investigate the differences between patients with critical anti-NMDAR encephalitis with SE and patients who experienced epileptic seizures without SE and to evaluate the long-term disease outcomes of patients with anti-NMDAR encephalitis with SE who were admitted to the neurological intensive care unit (neuro-ICU).

Methods: In this retrospective study based on a prospective registry, patients with anti-NMDAR encephalitis with neuro-ICU admission from 2014 to 2019 were analyzed and divided into two groups based on whether they had SE. Their clinical characteristics during the neuro-ICU stay were assessed and compared. The neurological and seizure outcomes were evaluated every 3 months.

Results: Of 83 patients with anti-NMDAR encephalitis, 24 required intensive care. In the SE group, 38.5% (5 of 13) of patients developed refractory SE (RSE), and 21.3% (3 of 13) of patients developed super RSE. More patients in the SE group presented with seizures as the initial symptoms (53.8% vs. 9.1%, p = 0.033) and had a strong positive NMDAR antibody titer in the cerebrospinal fluid (76.9% vs. 27.3%, p = 0.043). More patients in the non-SE group had a good neurological outcome (modified Rankin Scale (mRS) score < 2) at 3 months after disease onset (60.0% vs. 15.4%, p = 0.039), but 83.3% of patients with SE had a mRS score < 2 at 9 months after disease onset, which was similar to the rate in the non-SE group. A total of 41.7% of patients with SE had their last seizure within 1 month from disease onset, which was significantly lower than the rate in the non-SE group (90%), but all the patients with SE became seizure free after the acute phase of disease.

Conclusions: Patients with critical anti-NMDAR encephalitis who present with SE have a high rate of RSE/super RSE and recover more slowly than patients without SE, but most of them will eventually achieve good long-term neurological outcomes and live seizure free after the acute phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12028-021-01283-4DOI Listing
July 2021

Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.

J Exp Med 2021 09 13;218(9). Epub 2021 Jul 13.

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20202350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282281PMC
September 2021

GRMT: Generative Reconstruction of Mutation Tree From Scratch Using Single-Cell Sequencing Data.

Front Genet 2021 4;12:692964. Epub 2021 Jun 4.

School of Information Engineering, Ningxia University, Yinchuan, China.

Single-cell sequencing (SCS) now promises the landscape of genetic diversity at single cell level, and is particularly useful to reconstruct the evolutionary history of tumor. There are multiple types of noise that make the SCS data notoriously error-prone, and significantly complicate tumor tree reconstruction. Existing methods for tumor phylogeny estimation suffer from either high computational intensity or low-resolution indication of clonal architecture, giving a necessity of developing new methods for efficient and accurate reconstruction of tumor trees. We introduce GRMT (Generative Reconstruction of Mutation Tree from scratch), a method for inferring tumor mutation tree from SCS data. GRMT exploits the -Dollo parsimony model to allow each mutation to be gained once and lost at most times. Under this constraint on mutation evolution, GRMT searches for mutation tree structures from a perspective of tree generation from scratch, and implements it to an iterative process that gradually increases the tree size by introducing a new mutation per time until a complete tree structure that contains all mutations is obtained. This enables GRMT to efficiently recover the chronological order of mutations and scale well to large datasets. Extensive evaluations on simulated and real datasets suggest GRMT outperforms the state-of-the-arts in multiple performance metrics. The GRMT software is freely available at https://github.com/qasimyu/grmt.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.692964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212059PMC
June 2021

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis.

Chin Med J (Engl) 2021 May 19;134(12):1457-1464. Epub 2021 May 19.

Department of Rheumatology, Renji Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 200000, China.

Background: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.

Methods: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.

Results: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.

Conclusions: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.

Trial Registration: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CM9.0000000000001527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213301PMC
May 2021

Effect of care bundles on postoperative pain, negative emotions, and self-care ability of patients with acute dacryocystitis.

Am J Transl Res 2021 15;13(4):2794-2803. Epub 2021 Apr 15.

Department of Ophthalmology, The First Affiliated Hospital of Chongqing, Chongqing Key Laboratory of Ophthalmology, Chongqing Institute of Ophthalmology Chongqing 400069, China.

Aim: This study aimed to investigate the effect of care bundles on the postoperative pain, negative emotions, and self-care ability of patients with acute dacryocystitis.

Methods: We recruited 103 patients with acute dacryocystitis undergoing surgery in our hospital from July 2018 to October 2019 in this study. Among them, 55 patients received care bundles (the research group, RG) and the other 48 received conventional care (the control group, CG). The two groups were compared in response rate, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Exercise of Self-Care Agency Scale (ESCA) before and after nursing interventions, as well as postoperative Visual Analogue Scale (VAS), MOS 36-item short-form health survey (SF-36), and patient satisfaction rate.

Results: After the care, the RG had a markedly higher response rate than the CG. No significant differences were found in SAS and SDS scores between the two groups before nursing care, and lower scores were found in the RG after the care. There was no significant difference in VAS scores before nursing care, and the RG showed higher scores than the CG after the care. There was no significant difference in self-care skills, self-care responsibility, self-concept, health knowledge, and self-care ability between the two groups before nursing care, but they all increased after the care. Markedly higher scores of SF-36 and a higher patient satisfaction rate were observed in the RG after the care.

Conclusion: Care bundles can enhance the self-care ability of patients with acute dacryocystitis after surgery, reduce pain intensity, relieve negative emotions, improve quality of life, and increase patient satisfaction with nursing care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129262PMC
April 2021

PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer's Disease Trans-Mitochondrial Cybrid Cells.

J Alzheimers Dis 2021 ;81(4):1749-1761

Department of Surgery, Columbia University New York, NY, USA.

Background: Mitochondrial dysfunction, bioenergetic deficit, and extensive oxidative stress underlie neuronal perturbation during the early stage of Alzheimer's disease (AD). Previously, we demonstrated that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with AD pathology in AD-affected human brains and AD mice.

Objective: In the present study, we highlight the essential role of PINK1 in AD-relevant mitochondrial perturbation and neuronal malfunction.

Methods: Using trans-mitochondrial "cybrid" (cytoplasmic hybrid) neuronal cells, whose mitochondria are transferred from platelets of patients with sporadic AD, we observed the effect of PINK1 in neuronal-like differentiation and synaptogenesis and mitochondrial functions.

Results: In AD cybrid cells, the downregulation of PINK1 is correlated to the alterations in mitochondrial morphology and function and deficit in neuronal-like differentiation. Restoring/increasing PINK1 by lentivirus transduction of PINK1 robustly attenuates mitochondrial defects and rescues neurite-like outgrowth. Importantly, defective PINK1 kinase activity fails to reverse these detrimental effects. Mechanistically, AD cybrid cells reveal a significant decrease in PINK1-dependent phosphorylated mitofusin (Mfn) 2, a key mitochondrial membrane protein that participates in mitochondrial fusion, and an insufficient autophagic activity for the clearance of dysfunctional mitochondria. Overexpression of PINK1, but not mutant PINK1 elevates phosphorylation of Mfn2 and autophagy signaling LC3-II. Accordingly, PINK1-overexpressed AD cybrids exhibit increases in mitochondrial length and density and suppressed reactive oxygen species. These results imply that activation of PINK1 protects against AD-affected mitochondrial dysfunction and impairment in neuronal maturation and differentiation.

Conclusion: PINK1-mediated mitophagy is important for maintaining mitochondrial health by clearance of dysfunctional mitochondria and therefore, improves energy homeostasis in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-210095DOI Listing
September 2021

Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease.

Aging Cell 2021 05 5;20(5):e13368. Epub 2021 May 5.

Department of Surgery, Columbia University, New York, NY, USA.

Mitochondrial dysfunction is one of the early pathological features of Alzheimer's disease (AD). Accumulation of cerebral and mitochondrial Aβ links to mitochondrial and synaptic toxicity. We have previously demonstrated the mechanism by which presequence peptidase (PITRM1)-mediated clearance of mitochondrial Aβ contributes to mitochondrial and cerebral amyloid pathology and mitochondrial and synaptic stress in adult transgenic AD mice overexpressing Aβ up to 12 months old. Here, we investigate the effect of PITRM1 in an advanced age AD mouse model (up to 19-24 months) to address the fundamental unexplored question of whether restoration/gain of PITRM1 function protects against mitochondrial and synaptic dysfunction associated with Aβ accumulation and whether this protection is maintained even at later ages featuring profound amyloid pathology and synaptic failure. Using newly developed aged PITRM1/Aβ-producing AD mice, we first uncovered reduction in PITRM1 expression in AD-affected cortex of AD mice at 19-24 months of age. Increasing neuronal PITRM1 activity/expression re-established mitochondrial respiration, suppressed reactive oxygen species, improved synaptic function, and reduced loss of synapses even at advanced ages (up to 19-24 months). Notably, loss of PITRM1 proteolytic activity resulted in Aβ accumulation and failure to rescue mitochondrial and synaptic function, suggesting that PITRM1 activity is required for the degradation and clearance of mitochondrial Aβ and Aβ deposition. These data indicate that augmenting PITRM1 function results in persistent life-long protection against Aβ toxicity in an AD mouse model. Therefore, augmenting PITRM1 function may enhance Aβ clearance in mitochondria, thereby maintaining mitochondrial integrity and ultimately slowing the progression of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135081PMC
May 2021

Immunological effect of irreversible electroporation on hepatocellular carcinoma.

BMC Cancer 2021 Apr 21;21(1):443. Epub 2021 Apr 21.

Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE).

Methods: We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice.

Results: We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4 T cell subsets, but not CD8, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8 T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group.

Conclusions: Our study demonstrated that IRE upregulated activated T cells and downregulated Tregs in the peripheral blood of patients. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by the infiltration of cytotoxic CD8 T cells into the tumors, accompanied by reduced Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08176-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061072PMC
April 2021

Cutaneous Ulceration and Digital Gangrene in an Anti-MDA5-positive Overlap Myositis.

Rheumatology (Oxford) 2021 Mar 22. Epub 2021 Mar 22.

Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab284DOI Listing
March 2021

The effect of perineural dexamethasone on rebound pain after ropivacaine single-injection nerve block: a randomized controlled trial.

BMC Anesthesiol 2021 02 12;21(1):47. Epub 2021 Feb 12.

Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Rebound pain after a single-shot nerve block challenges the real benefit of this technique. We aimed to investigate whether perineural dexamethasone addition decreased the incidence of rebound pain after a single-shot nerve block.

Methods: We randomly allocated 132 patients scheduled for open reduction internal fixation of an upper extremity closed fracture under single-shot peripheral nerve block and sedation into two groups. Patients in the dexamethasone group received nerve block with 0.375% ropivacaine and 8 mg dexamethasone, while those in the control group received ropivacaine only. Sixty-three patients in the dexamethasone group and 60 patients in the control group were analyzed for the incidence of rebound pain 48 h after block administration, which was the primary outcome. The secondary outcomes included the highest self-reported numeric rating scale (NRS) pain score, and NRS at 8, 12, 24, and 48 h after the block, sufentanil consumption, sleep quality on the night of surgery, patient satisfaction with the pain therapy, blood glucose at 6 h after the block, pain and paresthesia at 30 days after surgery.

Results: The incidence of rebound pain was significantly lower in the dexamethasone group (7 [11.1%] of 63 patients) than in the control group (28 [48.8%] of 60 patients [RR = 0.238, 95% CI (0.113-0.504), p = 0.001]. Dexamethasone decreased opioid consumption in 24 h after surgery (p < 0.001) and improved the sleep quality score on the night of surgery (p = 0.01) and satisfaction with pain therapy (p = 0.001). Multivariate logistic regression analysis showed that only group allocation was associated with the occurrence of rebound pain [OR = 0.062, 95% CI (0.015-0.256)]. Patients in the dexamethasone group reported later onset pain (19.7 ± 6.6 h vs 14.7 ± 4.8 h since block administration, mean ± SD, p < 0.001) and lower peak NRS scores [5 (3, 6) vs 8 (5, 9), median (IQR), p < 0.001] than those in the control group.

Conclusions: The perineural administration of 8 mg dexamethasone reduces rebound pain after a single-shot nerve block in patients receiving ORIF for an upper limb fracture.

Trial Registration: This study was retrospectively registered in the Chinese Clinical Trial Registry ( ChiCTR-IPR-17011365 ) on May 11th, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-021-01267-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879628PMC
February 2021

Depleting microRNA-183-3p improves renal tubulointerstitial fibrosis after acute kidney injury via SIRT1/PUMA/FOXO3a deacetylation.

Life Sci 2021 Mar 12;269:119017. Epub 2021 Jan 12.

Department of Nephrology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China. Electronic address:

Background/aim: Emerging studies have revealed the mechanism of microRNAs (miRNAs) in acute kidney injury (AKI). However, almost no research focuses on miR-183-3p in AKI. Therefore, this study is started to explore the potential role of miR-183-3p from the perspective of Sirtuin (SIRT1)/forkhead box O3a (FOXO3a)/p53 up-regulated modulator of apoptosis (PUMA) in AKI.

Methods: AKI rat models were established. miR-183-3p, SIRT1, deacetylated FOXO3a and PUMA expression in AKI were detected. The targeting relationship between miR-183-3p and SIRT1 was tested. AKI modeled rats were injected with miR-183-3p- or SIRT1-related sequences to identify their effects on AKI. Rat renal tubular epithelial cells NRK-52E were transfected with miR-183-3p- or SIRT1-related sequences for further exploration of their roles in vitro.

Results: Decreased SIRT1 and deacetylated FOXO3a and increased miR-183-3p and PUMA were found in AKI. SIRT1 was targeted by miR-183-3p. Down-regulated miR-183-3p or up-regulated SIRT1 attenuated renal tissue damage and fibrosis, and suppressed renal tubular epithelial cell apoptosis in renal tissues of AKI rats. Down-regulated miR-183-3p or up-regulated SIRT1 promoted proliferation and impaired fibrosis and apoptosis of renal tubular epithelial cells.

Conclusion: Our study provides evidence that down-regulated miR-183-3p or up-regulated SIRT1 attenuates AKI via PUMA inhibition induced by FOXO3a deacetylation. Thus, miR-183-3p and SIRT1 can be the candidates for therapy of AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119017DOI Listing
March 2021

miR-218 contributes to drug resistance in multiple myeloma via targeting LRRC28.

J Cell Biochem 2021 04 8;122(3-4):305-314. Epub 2021 Jan 8.

Cognitive Impairment Ward of Neurology Department, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.

Multiple myeloma (MM) is a malignant neoplasm featured by obvious drug resistance and poor prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs with crucial roles in many biological processes including cancer initiation and progression. The current study aims to investigate the pathogenic role and molecular mechanism of miRNAs in MM drug resistance. In the present study, The expression profile of miRNAs in MM samples was analyzed by microarray and real-time polymerase chain reaction. Protein expressions were detected by Western blot analysis. Cell apoptosis was detected by the Annexin V staining assay. The interaction between miRNA and the targeting mRNA was assessed using Dual luciferase reporter assay. Herein, we show that expression profile of miRNAs is deregulated in MM. miR-218, one of the most aberrational miRNAs in MM, is significantly decreased in MM cells compared to peripheral blood mononuclear cell (PBMC). Genetic manipulation reveals miR-218 control the response of MM cells to anticancer drug bortezomib (BTZ). Overexpression of miR-218 causes a significant aberrant genes expression including leucine rich repeat containing 28 (LRRC28). Mechanistic study shows that miR-218 control the drug response through mediating the expression of LRRC28 in MM cells. Overexpression of LRRC28 significantly reserves miR-218-mediated cell response to BTZ. Taken together, miR-218 is decreased in MM that contributes to BTZ resistance via targeting LRRC28, which might be used as a novel therapeutic target for multiple myeloma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.29684DOI Listing
April 2021

A novel method for identifying hotspots and forecasting air quality through an adaptive utilization of spatio-temporal information of multiple factors.

Sci Total Environ 2021 Mar 14;759:143513. Epub 2020 Nov 14.

Institute of Future Cities, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Geography and Resource Management, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address:

Air pollution exerts serious impacts on human health and sustainable development. The accurate forecasting of air quality can guide the formulation of mitigation strategies and reduce exposure to air pollution. It is beneficial to explicitly consider both spatial and temporal information of multiple factors, e.g., the meteorological data, in the forecasting of air pollutant concentrations. The temporal information of relevant factors collected at a location should be considered for forecasting. In addition, these factors recorded at other locations may also provide useful information. Existing methods utilizing the spatio-temporal information of these relevant factors are usually based on some very complicated frameworks. In this study, we propose a novel and simple spatial attention-based long short-term memory (SA-LSTM) that combines LSTM and a spatial attention mechanism to adaptively utilize the spatio-temporal information of multiple factors for forecasting air pollutant concentrations. Specifically, the SA-LSTM employs gated recurrent connections to extract temporal information of multiple factors at individual locations, and the spatial attention mechanism to spatially fuse the temporal information extracted at these locations. This method is effective and applicable to forecast any air pollutant concentrations when spatio-temporal information of relevant factors has to be utilized. To validate the effectiveness of the proposed SA-LSTM, we apply it to forecast the daily air quality in Hong Kong, a high density city with peculiar cityscapes, by using the air quality and meteorological data. Empirical results demonstrate that the proposed SA-LSTM outperforms the conventional models with respect to one-day forecast accuracy, especially for extreme values. Moreover, the attention weights learned by the SA-LSTM can identify hotspots of the air pollution process for reducing computational complexity of forecasting and provide a better understanding of the underlying mechanism of air pollution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.143513DOI Listing
March 2021

Contributions of PARP-1 rs1136410 C>T polymorphism to the development of cancer.

J Cell Mol Med 2020 12 27;24(24):14639-14644. Epub 2020 Oct 27.

Emergency and Critical Care Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in the DNA damage response. SNP rs1136410 C>T, the most studied polymorphism in PARP-1 gene, is highly implicated in the susceptibility of cancer. However, the roles of PARP-1 rs1136410 C>T on cancer risk vary from different studies. We comprehensively screened all qualified publications from several databases, including PubMed, EMBASE, MEDLINE, CNKI and Wanfang. The searching was updated to April 2020. Our meta-analysis included 60 articles with 65 studies, comprised of a total of 23 996 cases with cancer and 33 015 controls. Overall, pooled data showed that the PARP-1 rs1136410 C>T polymorphism was significantly but a border-line associated with an increased risk of overall cancer (CC vs. TT/TC: OR = 1.11, 95% CI = 1.00-1.24; C vs T: OR = 1.07, 95% CI = 1.01-1.14). Subgroup analysis indicated that rs1136410 C allele contributed to high risk among gastric, thyroid, and cervical cancer, but lower risk among brain cancer. Furthermore, increased cancer risk was detected in the subgroups of Asian, controls from population-based design studies, and HWE ≤ 0.05 studies. Sensitivity analysis and Egger's test showed that results of the meta-analysis were fairly stable. The current study indicated that PARP1 rs1136410 C>T polymorphism may have an impact on certain types of cancer susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753995PMC
December 2020

CircRNA ITCH increases bortezomib sensitivity through regulating the miR-615-3p/PRKCD axis in multiple myeloma.

Life Sci 2020 Dec 5;262:118506. Epub 2020 Oct 5.

Ultrasound Department, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China. Electronic address:

Aims: Bortezomib (BTZ) is described as the first-line agent for multiple myeloma (MM) chemotherapy, but the emergence of BTZ resistance usually results in the failure of chemotherapy in MM. Circular RNA (circRNA) itchy E3 ubiquitin protein ligase (circITCH) is a novel identified circRNA that plays a vital role in the development of human cancers. However, the role of circITCH in the development of BTZ resistance in MM remains elusive.

Materials And Methods: The expression of circITCH, miR-615-3p, and protein kinase C, delta (PRKCD) was detected with quantitative reverse transcription PCR and western blot. The effects of circITCH on the sensitivity of MM cells to BTZ were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, flow cytometry, and xenograft tumor assay. The interaction of circITCH, microRNA-615-3p, and PRKCD was explored using luciferase reporter assay and RNA immunoprecipitation assay.

Key Findings: circITCH was downregulated in MM bone marrow specimens and cell lines, as well as BTZ-resistant MM cells. Reduced expression of circITCH was indicative of poor prognosis in MM patients. Upregulation of circITCH enhanced the sensitivity of BTZ-resistant MM cells to BTZ in vitro and in vivo. Furthermore, circITCH was identified as a sponge for miR-615-3p, and PRKCD is confirmed as a direct target of miR-615-3p. Besides, circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis.

Significance: circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis, providing a novel potential target for combating BTZ resistance in patients with MM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118506DOI Listing
December 2020

Contrasted patterns of local adaptation to climate change across the range of an evergreen oak, .

Evol Appl 2020 Oct 9;13(9):2377-2391. Epub 2020 Jun 9.

Canada Research Chair in Integrative Biology of Northern Flora Université du Québec à Rimouski Rimouski QC Canada.

Long-lived tree species are genetically differentiated and locally adapted with respect to fitness-related traits, but the genetic basis of local adaptation remains largely unresolved. Recent advances in population genetics and landscape genomic analyses enable identification of putative adaptive loci and specific selective pressures acting on local adaptation. Here, we sampled 60 evergreen oak () populations throughout the species' range and pool-sequenced 587 individuals at drought-stress candidate genes. We analyzed patterns of genetic diversity and differentiation for 381 single nucleotide polymorphisms (SNPs) from 65 candidate genes and eight microsatellites. Outlier loci were identified by genetic differentiation analysis and genome-environment associations. The response pattern of genetic variation to environmental gradient was assessed by linear isolation-by-distance/environment tests, redundancy analysis, and nonlinear methods. SNPs and microsatellites revealed two genetic lineages: Tibet and Hengduan Mountains-Western Sichuan Plateau (HDM-WSP), with reduced genetic diversity in Tibet lineage. More outlier loci were detected in HDM-WSP lineage than Tibet lineage. Among these, three SNPs in two genes responded to dry season precipitation in the HDM-WSP lineage but not in Tibet. By contrast, genetic variation in the Tibet lineage was related to geographic distance instead of the environment. Furthermore, risk of nonadaptedness (RONA) analyses suggested HDM-WSP lineage will have a better capacity to adapt in the predicted future climate compared with the Tibet lineage. We detected genetic imprints consistent with natural selection and molecular adaptation to drought on the Qinghai-Tibet Plateau (QTP) over a range of long-lived and widely distributed oak species in a changing environment. Our results suggest that different within-species adaptation processes occur in species occurring in heterogeneous environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eva.13030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513717PMC
October 2020

Restoration of circPSMC3 sensitizes gefitinib-resistant esophageal squamous cell carcinoma cells to gefitinib by regulating miR-10a-5p/PTEN axis.

Cell Biol Int 2021 Jan 12;45(1):107-116. Epub 2020 Oct 12.

Translational Research Institute, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, China.

Circular RNAs (circRNAs) has been shown to play an important role in the progression of various cancers. However, the function and underlying mechanisms of circRNAs affecting chemotherapy resistance in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In this study, we used gefitinib-resistant (GR) ESCC cells to investigate the function of circPSMC3 and clarify the underlying mechanism in chemotherapy resistance in ESCC. The results suggested that circPSMC3 expression was downregulated, but miR-10a-5p was upregulated in ESCC tissues and cells, as well as in GR ESCC cells. CircPSMC3 overexpression increased the sensitivity of ESCC cells to gefitinib, as indicated by reduced half maximal inhibitory concentration value, increased apoptosis rate and cleaved caspase-3 protein expression. CircPSMC3 directly interacted with miR-10a-5p and inhibited the expression of miR-10a-5p. Phosphatase and tensin homolog (PTEN) was a direct target of miR-10a-5p and circPSMC3 promoted PTEN expression via decreasing miR-10a-5p level. Moreover, the effect of circPSMC3 on resistance of GR ESCC cells to gefitinib was remarkably reduced by restoration of miR-10a-5p and downregultion of PTEN. Taken together, these observations suggested that upregulation of circPSMC3 overcame resistance of GR ESCC cells to gefitinib by modulating the miR-10a-5p/PTEN axis, which provide a new therapeutic strategy for overcoming gefitinib resistance in ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbin.11473DOI Listing
January 2021

Integration of Pleurotus tuoliensis cultivation and biogas production for utilization of lignocellulosic biomass as well as its benefit evaluation.

Bioresour Technol 2020 Dec 25;317:124042. Epub 2020 Aug 25.

Shandong Provincial Key Laboratory of Agricultural Microbiology, College of Plant Protection, Shandong Agricultural University, Tai'an 271018, China.

The present study was to assess the economic benefit of integrated P. tuoliensis cultivation and biogas production based on the utilization of lignocellulosic biomass. Among the five evaluated cultivation substrates, that consisting of 55% cottonseed hull, 25% corncob, 10% wheat bran, 5% corn flour, 4% lime, and 1% gypsum was demonstrated to be optimal for the simultaneous production of P. tuoliensis mushrooms and biogas fuel. Preliminary estimation shows that, for the consumption of dry substrate per unit mass (calculated in per kg), a total of 561 g fresh mushroom product was harvested and 189.88 L biogas was generated. Accordingly, the production costs were abolished and an economic benefit of approximately $0.592 was obtained, with the high-value mushroom product being the main contributor to profit. Moreover, this integrated process also exhibited positive ecological and social benefits and as such, is worthy of promotion and further application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2020.124042DOI Listing
December 2020

Corrigendum to "Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-related orphan receptor-α" [Int. Immunopharmacol. 83 (2020) 106365].

Int Immunopharmacol 2020 Sep 28;86:106817. Epub 2020 Jul 28.

Department of Rheumatology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.106817DOI Listing
September 2020

SimuSCoP: reliably simulate Illumina sequencing data based on position and context dependent profiles.

BMC Bioinformatics 2020 Jul 23;21(1):331. Epub 2020 Jul 23.

Hefei National Laboratory for Physical Sciences at Microscale, USTC-SJH Joint Center for Human Reproduction and Genetics, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.

Background: A number of simulators have been developed for emulating next-generation sequencing data by incorporating known errors such as base substitutions and indels. However, their practicality may be degraded by functional and runtime limitations. Particularly, the positional and genomic contextual information is not effectively utilized for reliably characterizing base substitution patterns, as well as the positional and contextual difference of Phred quality scores is not fully investigated. Thus, a more effective and efficient bioinformatics tool is sorely required.

Results: Here, we introduce a novel tool, SimuSCoP, to reliably emulate complex DNA sequencing data. The base substitution patterns and the statistical behavior of quality scores in Illumina sequencing data are fully explored and integrated into the simulation model for reliably emulating datasets for different applications. In addition, an integrated and easy-to-use pipeline is employed in SimuSCoP to facilitate end-to-end simulation of complex samples, and high runtime efficiency is achieved by implementing the tool to run in multithreading with low memory consumption. These features enable SimuSCoP to gets substantial improvements in reliability, functionality, practicality and runtime efficiency. The tool is comprehensively evaluated in multiple aspects including consistency of profiles, simulation of genomic variations and complex tumor samples, and the results demonstrate the advantages of SimuSCoP over existing tools.

Conclusions: SimuSCoP, a new bioinformatics tool is developed to learn informative profiles from real sequencing data and reliably mimic complex data by introducing various genomic variations. We believe that the presented work will catalyse new development of downstream bioinformatics methods for analyzing sequencing data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-020-03665-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379788PMC
July 2020

NeuroD1 Dictates Tumor Cell Differentiation in Medulloblastoma.

Cell Rep 2020 06;31(12):107782

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA. Electronic address:

Tumor cells are characterized by unlimited proliferation and perturbed differentiation. Using single-cell RNA sequencing, we demonstrate that tumor cells in medulloblastoma (MB) retain their capacity to differentiate in a similar way as their normal originating cells, cerebellar granule neuron precursors. Once they differentiate, MB cells permanently lose their proliferative capacity and tumorigenic potential. Differentiated MB cells highly express NeuroD1, a helix-loop-helix transcription factor, and forced expression of NeuroD1 promotes the differentiation of MB cells. The expression of NeuroD1 in bulk MB cells is repressed by trimethylation of histone 3 lysine-27 (H3K27me3). Inhibition of the histone lysine methyltransferase EZH2 prevents H3K27 trimethylation, resulting in increased NeuroD1 expression and enhanced differentiation in MB cells, which consequently reduces tumor growth. These studies reveal the mechanisms underlying MB cell differentiation and provide rationales to treat MB (potentially other malignancies) by stimulating tumor cell differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.107782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357167PMC
June 2020

The Effects of Propofol on Neural Responses in the Mouse Primary Auditory Cortex.

J Neurosurg Anesthesiol 2020 Jun 19. Epub 2020 Jun 19.

Department of Anesthesiology, Zhongshan Hospital, Fudan University.

Objective: Two-photon laser-scanning microscopy allows for the monitoring of all brain neurons with single-cell and single-action potential accuracy. This study aimed to investigate the neural responses of the primary auditory cortex to sound stimuli in awake and propofol-anesthetized mice using 2-photon laser-scanning microscopy.

Methods: Twelve healthy adult male C57BL/6 mice were used in the present study. In each mouse, the scalp was removed over the entire dorsal skull, and the right primary auditory cortex (A1) located. The test stimulus, used in the awake and propofol-induced anesthetic state, was a group of tones with a random combination of 3 sound intensities and 8 sound frequencies. The calcium indicator GCaMP6s was virally expressed in cortical neurons and neuronal activity was recorded using 2-photon imaging.

Results: Calcium responses to sound stimuli in two thirds of the neuronal population of the A1 layer were significantly inhibited by propofol anesthesia. In a single neuron, the calcium responses were also inhibited by propofol anesthesia. In the waking state, △F/F (where F is the time series of fluorescence intensity) of all single neurons was significantly higher than that in the propofol-induced anesthetic state (n=669, P<0.001). Finally, in one example session and averaged across different fields of views (n=6 sessions), the response events to sound stimuli were also inhibited by propofol anesthesia.

Conclusion: Anesthetic doses of propofol inhibited calcium transients and neuronal activity in the primary auditory cortex of mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ANA.0000000000000709DOI Listing
June 2020

Data relating to sequencing statistics and the reads and genomic coverage aligning to Taenia solium in the cerebrospinal fluid.

Data Brief 2020 Aug 15;31:105700. Epub 2020 May 15.

Department of Neurology, Xijing Hospital, The Fourth Military Medical University, 15 Changle xi Road, Xi'an 710032, China.

This data can serve as a reference for other next-generation sequencing (NGS) of the cerebrospinal fluid (CSF). In the related research article, entitled "Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Neurocysticercosis", we reported NGS of the CSF might be an auxiliary method for neurocysticercosis (NCC) patients who have complicated manifestations and courses to receive early diagnosis and treatment. In this article, we retrieved the available data about the sequencing statistics of the CSF samples and the number of unique reads and genomic coverage aligning to microorganic sequences. The data were generated by the Illumina MiniSeq system for sequencing and computational subtraction of the human host sequences was performed. Finally, the remaining sequencing data were aligned to the Microbial Genome Databases. This data can serve as a reference for other NGS of the CSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2020.105700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248648PMC
August 2020

Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells.

J Neurooncol 2020 Jun 21;148(2):259-271. Epub 2020 May 21.

Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, USA.

Introduction: The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear.

Methods: We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI-IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action.

Results: TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite.

Conclusions: As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03538-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316845PMC
June 2020

Restoration of UPK1A-AS1 Expression Suppresses Cell Proliferation, Migration, and Invasion in Esophageal Squamous Cell Carcinoma Cells Partially by Sponging microRNA-1248.

Cancer Manag Res 2020 21;12:2653-2662. Epub 2020 Apr 21.

Translational Research Institute, Henan University, Kaifeng, Henan Province, People's Republic of China.

Background: Recent evidence suggests that long non-coding RNAs (lncRNAs) are emerging as key determinants of esophageal squamous cell carcinoma (ESCC) progression. This study aimed to investigate the role of lncRNA UPK1A antisense RNA 1 (UPK1A-AS1) in ESCC cell proliferation, invasion, and migration.

Methods: The expression levels of UPK1A-AS1 and miR-1248 were determined using quantitative reverse transcriptase-polymerase chain reaction. The functional role of UPK1A-AS1 in ESCC was investigated using subcellular localization assay, Cell Counting Kit-8 assay, colony formation assay, scratch-healing assay, and transwell invasion assay. The functional interaction between UPK1A-AS1 and miR-1248 was assessed using luciferase reporter and RNA pull-down assays.

Results: Twenty dysregulated lncRNAs were detected in ESCC. Downregulation of UPK1A-AS1 was observed in ESCC tissues and cell lines. Functionally, upregulation of UPK1A-AS1 suppressed the proliferation, migration, and invasion of ESCC cells. Moreover, an inverse correlation between UPK1A-AS1 and miR-1248 expression was observed in ESCC specimens, and miR-1248 was identified as a direct target of UPK1A-AS1. Furthermore, we found that UPK1A-AS1 exerts its anti-cancer effects partially through sponging miR-1248 in ESCC cells.

Conclusion: UPK1A-AS1 suppressed the proliferation, migration, and invasion of ESCC cells partially by sponging miR-1248. Hence, our findings provide novel insights into the regulatory pathway involved in ESCC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S239418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186006PMC
April 2020

Iguratimod as an alternative induction therapy for refractory lupus nephritis: a preliminary investigational study.

Arthritis Res Ther 2020 03 30;22(1):65. Epub 2020 Mar 30.

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, 145 Shandong RD, Shanghai, 200001, China.

Objectives: Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN).

Methods: We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up.

Results: The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0-10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod.

Conclusions: Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02154-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106733PMC
March 2020

Thermally sensitive fluorescence imaging system for radiofrequency ablation guidance.

Int J Hyperthermia 2020 ;37(1):308-315

Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Radiofrequency ablation (RFA) has been clinically used as a minimally invasive procedure for the treatment of many solid tumors. However, the current imaging techniques have some shortages in RFA guidance, especially for the assessment of the margin of ablation. Herein, we developed a novel optical imaging platform to guide RFA utilizing fluorescence resonance energy transfer from a thermally sensitive fluorescent protein conjugated to a near-infrared fluorescent dye. Additionally, attaching receptor-targeting ligands further equipped the system with high specificity to tumors overexpressing the targeted receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02656736.2020.1742934DOI Listing
October 2020
-->