Publications by authors named "Jun Qi"

439 Publications

Human Leukocyte Antigen Class I Association with Occult Hepatitis B Virus Infection in Shaanxi Han Group: Analysis at the Haplotype Level.

J Gene Med 2021 Oct 13:e3393. Epub 2021 Oct 13.

HLA Typing Laboratory, Blood Center of the Shaanxi Province, Institute of Xi'an Blood Bank, Xi'an, Shaanxi Province, China.

Background: Previous researches have confirmed that human leucocyte antigen (HLA) class I genes and haplotypes were correlation with hepatitis B virus (HBV) infection. Occult HBV infection (OBI), a special type of chronic HBV infection, is defined as HBV surface antigen (HBsAg) negative patients with or without serologic markers by the means of HBV DNA detection in human plasma or in liver tissue by diagnostic test. So far, the associations of HLA I haplotypes with OBI have not been reported previously in China.

Methods: A case-control study between 107 OBI subjects and 280 healthy controls from blood donors in Blood Center of the Shaanxi Province was conducted in present association analysis. The HLA-A, -B, -C loci of case-control subjects were detected and genotyped by polymerase chain reaction-sequence based typing (PCR-SBT). And the HLA-A, -B, -C haplotypic frequencies were calculated by maximum likelihood method.

Results: The HLA-A*33:03-C*07:01G (Pc=0.039, OR=8.996, 95%CI=1.825-44.338), B*44:03-C*07:01G (Pc=0.0069, OR=12.000, 95%CI=2.507-57.436), A*33:03-B*44:03-C*07:01G (Pc=0.04, OR=7.094, 95%CI=1.387-36.288) haplotypes showed significant positive associated with OBI. Independent effects demonstrated that HLA-B*44:03 and HLA-C*07:01G gave the main contribution to risk, whereas HLA-A*33:03 was associated only by linkage disequilibrium (LD).

Conclusions: This study for the first time demonstrated that HLA I haplotypes were associated with OBI in Shaanxi Han population. The present results suggest that HLA-B*44:03-C*07:01G might be a potential risk factor for OBI.
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http://dx.doi.org/10.1002/jgm.3393DOI Listing
October 2021

Targeting an inducible SALL4-mediated cancer vulnerability with sequential therapy.

Cancer Res 2021 Sep 30. Epub 2021 Sep 30.

Pathology, Brigham and Women's Hospital

Oncofetal protein SALL4 is critical for cancer cell survival. Targeting SALL4, however, is only applicable in a fraction of cancer patients that are positive for this gene. To overcome this limitation, we propose to induce a cancer vulnerability by engineering a partial dependency upon SALL4. Following exogenous expression of SALL4, SALL4-negative cancer cells became partially dependent on SALL4. Treatment of SALL4-negative cells with the FDA-approved hypomethylating agent 5-Aza-2'-deoxycytidine (DAC) resulted in transient upregulation of SALL4. DAC pre-treatment sensitized SALL4 negative cancer cells to Entinostat, which negatively affected SALL4 expression through a microRNA, miRNA-205, both in culture and in vivo. Moreover, SALL4 was essential for the efficiency of sequential treatment of DAC and Entinostat. Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0030DOI Listing
September 2021

[Clinical application of split three-dimensional printing patient-specific instrumentation in medial open-wedge high tibial osteotomy].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Sep;35(9):1119-1124

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha Hunan, 410008, P.R.China.

Objective: To investigate the accuracy of split three-dimensional (3D) printing patient-specific instrumentation (PSI) in medial open-wedge high tibial osteotomy (MOWHTO) and its effectiveness in treating medial knee osteoarthritis.

Methods: Clinical data of 14 patients with medial knee osteoarthritis and treated with split 3D printing PSI-assisted MOWHTO between August 2019 and August 2020 were retrospectively analyzed. There were 5 males and 9 females with an average age of 61 years (range, 43-68 years). The disease duration ranged from 1 to 16 years, with an average of 4.7 years. Preoperative Kellgren-Lawrence grading of knee osteoarthritis included grade Ⅰ in 2 cases, grade Ⅱ in 6 cases, and grade Ⅲ in 6 cases. The Hospital for Special Surgery (HSS) score was 59.1±4.9. The weight bearing line ratio (WBL), hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), posterior tibial slope angle (PTSA), and actual correction angle of the lower limbs were measured on postoperative imaging data, and compared with the preoperative measurements and the designed target values to evaluate the accuracy of the PSI-assisted surgery. The patients' knee function were evaluated with the HSS score at 3 and 6 months postoperatively, and at last follow-up.

Results: One patient suffered from an incision exudation at 2 weeks postoperatively, and the incision healed after symptomatic treatment. The incisions of other patients healed by first intention. All patients were followed up 7-19 months (mean, 14.8 months). There was no neural injuries, hinge fracture, plate or screw fractures, loosening, or other complications. The WBL was maintained at the postoperative level according to the X-ray examination during the follow-up period. The WBL, HKA, MPTA, and PTSA were all within a satisfactory range after operation. The WBL, HKA, and MPTA were significantly improved when compared with the preoperative measurements ( <0.05). There was no significant difference between preoperative and postoperative PTSA ( >0.05). The differences in postoperative WBL, HKA, MPTA, and correction angle compared with the preoperative designed target values were not significant ( >0.05). The HSS scores were 69.2±4.7, 77.7±4.3, and 88.1±5.4 at 3 and 6 months postoperatively, and last follow-up, respectively. The differences between time points were significant ( <0.05).

Conclusion: For patients with medial knee osteoarthritis, the split 3D printing PSI can assist the surgeon in MOWHTO with accurate osteotomy orthopedics and achieve favorable effectiveness.
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http://dx.doi.org/10.7507/1002-1892.202104001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444145PMC
September 2021

Correction: HDAC6 inhibitor WT161 downregulates growth factor receptors in breast cancer.

Oncotarget 2021 Aug 17;12(17):1736. Epub 2021 Aug 17.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

[This corrects the article DOI: 10.18632/oncotarget.19019.].
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http://dx.doi.org/10.18632/oncotarget.28051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378766PMC
August 2021

[Characterization of a rare HLA-C*08:84 allele and analysis of its 3-D molecular structure].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Aug;38(8):798-802

HLA Typing Laboratory, Shaanxi Provincial Blood Center, Xi'an, Shaanxi 710061, China.

Objective: To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure.

Methods: PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software.

Results: Analysis indicated that the rare allele (HLA-C*08:84) has transmitted from the proband's mother and has differed from HLA-C*08:01 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*08:84, C*08:01, C*08:02, C*08:03 and C*08:22 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively.

Conclusion: A rare HLA-C*08:84 allele has been identified, and its clinical significance has been analyzed.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200909-00655DOI Listing
August 2021

ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency.

Mol Cell 2021 09 5;81(17):3604-3622.e10. Epub 2021 Aug 5.

Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The transformed state in acute leukemia requires gene regulatory programs involving transcription factors and chromatin modulators. Here, we uncover an IRF8-MEF2D transcriptional circuit as an acute myeloid leukemia (AML)-biased dependency. We discover and characterize the mechanism by which the chromatin "reader" ZMYND8 directly activates IRF8 in parallel with the MYC proto-oncogene through their lineage-specific enhancers. ZMYND8 is essential for AML proliferation in vitro and in vivo and associates with MYC and IRF8 enhancer elements that we define in cell lines and in patient samples. ZMYND8 occupancy at IRF8 and MYC enhancers requires BRD4, a transcription coactivator also necessary for AML proliferation. We show that ZMYND8 binds to the ET domain of BRD4 via its chromatin reader cassette, which in turn is required for proper chromatin occupancy and maintenance of leukemic growth in vivo. Our results rationalize ZMYND8 as a potential therapeutic target for modulating essential transcriptional programs in AML.
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http://dx.doi.org/10.1016/j.molcel.2021.07.018DOI Listing
September 2021

Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy.

Leukemia 2021 Aug 2. Epub 2021 Aug 2.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.

Despite progress in the treatment of acute lymphoblastic leukemia (ALL), T-cell ALL (T-ALL) has limited treatment options, particularly in the setting of relapsed/refractory disease. Using an unbiased genome-scale CRISPR-Cas9 screen we sought to identify pathway dependencies for T-ALL which could be harnessed for therapy development. Disruption of the one-carbon folate, purine and pyrimidine pathways scored as the top metabolic pathways required for T-ALL proliferation. We used a recently developed inhibitor of SHMT1 and SHMT2, RZ-2994, to characterize the effect of inhibiting these enzymes of the one-carbon folate pathway in T-ALL and found that T-ALL cell lines were differentially sensitive to RZ-2994, with the drug inducing a S/G2 cell cycle arrest. The effects of SHMT1/2 inhibition were rescued by formate supplementation. Loss of both SHMT1 and SHMT2 was necessary for impaired growth and cell cycle arrest, with suppression of both SHMT1 and SHMT2 inhibiting leukemia progression in vivo. RZ-2994 also decreased leukemia burden in vivo and remained effective in the setting of methotrexate resistance in vitro. This study highlights the significance of the one-carbon folate pathway in T-ALL and supports further development of SHMT inhibitors for treatment of T-ALL and other cancers.
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http://dx.doi.org/10.1038/s41375-021-01361-8DOI Listing
August 2021

Gene Position Index Mutation Detection Algorithm Based on Feedback Fast Learning Neural Network.

Comput Intell Neurosci 2021 6;2021:1716182. Epub 2021 Jul 6.

Radiation & Cancer Biology Laboratory, Radiation Oncology Center, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.

In the detection of genome variation, the research on the internal correlation of reference genome is deepening; the detection of variation in genome sequence has become the focus of research, and it has also become an effective path to find new genes and new functional proteins. The targeted sequencing sequence is used to sequence the exon region of a specific gene in cancer gene detection, and the sequencing depth is relatively large. Traditional alignment algorithms will lose some sequences, which will lead to inaccurate mutation detection. This paper proposes a mutation detection algorithm based on feedback fast learning neural network position index. By establishing a position index relationship for ACGT in the DNA sequence, the subsequence is decomposed into the position relationship of different subsequences corresponding to the main sequence. The positional relationship of the subsequence in the main sequence is determined by the positional relationship. Analyzing SNP and InDel mutations, even structural mutations, through the position correlation of sequences has the advantages of high precision and easy implementation by personal computers. The feedback fast learning neural network is used to verify whether there is a linear relationship between two or more positions. Experimental results show that the mutation points detected by position index are more than those detected by Bcftools, Freebye, Vanscan2, and Gatk.
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http://dx.doi.org/10.1155/2021/1716182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279879PMC
July 2021

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

J Clin Lab Anal 2021 Sep 21;35(9):e23904. Epub 2021 Jul 21.

State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background And Aims: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC.

Methods: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera.

Results: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001).

Conclusions: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.
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http://dx.doi.org/10.1002/jcla.23904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418505PMC
September 2021

Mesenchymal stem cell-derived exosomes: therapeutic implications for rotator cuff injury.

Regen Med 2021 08 15;16(8):803-815. Epub 2021 Jul 15.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.

Rotator cuff injuries are a common clinical condition of the shoulder joint. Surgery that involves reattaching the torn tendon to its humeral head bony attachment has a somewhat lower success rate. The scar tissue formed during healing of the rotator cuff leads to poor tendon-related mechanical properties. To promote healing, a range of genetic interventions, as well as cell transplantation, and many other techniques have been explored. In recent years, the therapeutic promise of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies. Some data have suggested that MSCs can promote angiogenesis, reduce inflammation and cell proliferation and increase collagen deposition. These functions are likely paracrine effects of MSCs, particularly mediated through exosomes. Here, we review the use of MSCs-related exosomes in tissues and organs. We also discuss their potential utility for treating rotator cuff injuries, and explore the underlying mechanisms of their effects.
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http://dx.doi.org/10.2217/rme-2020-0183DOI Listing
August 2021

Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma.

Blood Cancer Discov 2021 07 10;2(4):370-387. Epub 2021 Apr 10.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA 02215.

Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3K4 trimethylation, a histone mark associated with activate gene transcription. We identify that KDM5A interacts with the P-TEFb complex and cooperates with MYC to control MYC targeted genes in multiple myeloma (MM) cells. We develop a cell-permeable and selective KDM5 inhibitor, JQKD82, that increases histone H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output and . Using genetic ablation together with our inhibitor, we establish that KDM5A supports MYC target gene transcription independent of MYC itself, by supporting TFIIH (CDK7)- and P-TEFb (CDK9)-mediated phosphorylation of RNAPII. These data identify KDM5A as a unique vulnerability in MM functioning through regulation of MYC-target gene transcription, and establish JQKD82 as a tool compound to block KDM5A function as a potential therapeutic strategy for MM.
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http://dx.doi.org/10.1158/2643-3230.BCD-20-0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265280PMC
July 2021

Use of physiological activities to estimate the population growth of rotifer (Brachionus calyciflorus) under the stress of toxic Microcystis and nitrite.

Chemosphere 2021 Jul 6;285:131419. Epub 2021 Jul 6.

Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, PR China.

Microcystis blooms disrupt aquatic systems and adversely affect zooplankton growth. Brachionus calyciflorus Pallas (rotifer) was introduced to different combinations of toxic Microcystis aeruginosa (0, 2 × 10, 2 × 10, and 2 × 10 cells mL) and nitrite (0, 2, 4, and 6 mg L) to evaluate their physiological activities and population growth under stress. Survival rate (S), population growth rate (r), grazing rate (G), antioxidant response, and metabolic and digestive enzyme activities were determined. Results revealed that G declined with the increasing nitrite doses and grazing time upon exposure to a certain Microcystis concentration. Toxic M. aeruginosa and nitrite inhibited the S, r, glutathione content, total antioxidant capacity level, and activities of alkaline phosphatase, xanthine oxidase, lactate dehydrogenase, and cellulase (p < 0.05) but increased the reactive oxygen species level, malondialdehyde content, and amylase activity (p < 0.05). The activities of superoxide dismutase, catalase, and pepsase were also increased in single low doses of nitrite solutions (p < 0.05). Therefore, the grazing intensity of rotifers affected B. calyciflorus physiological activities, which are useful in the estimation of its population growth in eutrophic water environments.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131419DOI Listing
July 2021

Partial inhibition of activin receptor-like kinase 4 alleviates bladder fibrosis caused by bladder outlet obstruction.

Exp Cell Res 2021 09 6;406(1):112724. Epub 2021 Jul 6.

Department of Urology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address:

The bladder undergoes profound structural alterations after bladder outlet obstruction (BOO), characterized by hypertrophy of the bladder wall and accumulation of extracellular matrix (ECM). Transforming growth factor-β (TGF-β) has been found to promote fibrosis of the bladder induced by partial bladder outlet obstruction (pBOO). Activin receptor-like kinase 4 (ALK4) is a downstream receptor of the TGF-β superfamily. However, the role of the ALK4-Smad2/3 pathway in the pathogenesis of bladder fibrosis caused by pBOO remains unknown. This study focused on learning the role of ALK4 in the process of bladder fibrosis caused by pBOO. The pBOO mice models showed that ALK4 expression was found to upregulate in the wild-type bladder 6 weeks after pBOO compared to control group. Then, mice with heterozygous knockout of the ALK4 gene (ALK4+/-) were generated. Histological analysis and Western blot (WB) results showed significant suppression of collagen expression in the bladders of ALK4+/- mice after pBOO compared with WT mice. WB also showed that ALK4+/- mice demonstrated significant suppression of phosphorylated Smad2/3 (p-Smad2/3) expression in the bladder 6 weeks after pBOO but not of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase or protein 38 (p-ERK, p-JNK, p-P38) expression. This effect might have occurred through partial inactivation of the Smad2/3 signaling pathway. In vitro, ALK4 overexpression promoted collagen production in cultured BSMCs and activated the Smad2/3 signaling pathway. Taken together, our results demonstrated that ALK4 insufficiency alleviated bladder fibrosis in a mouse model of pBOO partly by suppressing Smad2/3 activity.
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http://dx.doi.org/10.1016/j.yexcr.2021.112724DOI Listing
September 2021

Synthesis and Evaluation of Chiral Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors.

Med Chem 2021 Jun 28. Epub 2021 Jun 28.

Molecular Medicine Research Center, College of Phamacy, Yanbian University, Yanji 133002, China.

Background: TGF-β signaling pathway inhibition is considered an effective way to prevent the development of several diseases. In the design and synthesis of TGF-β inhibitors, a rhodanine compound containing a quinoxalinyl imidazole moiety was found to have strong antimicrobial activity.

Objective: The purpose of this work was to investigate the antimicrobial activity of other chiral rhodanine TGF-β inhibitors synthesized.

Methods: Two series of 3-substituted-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalinyl-6-yl)- 1H-imidazol-2-yl)methylene)-2-thioxothiazolin-4-ones (12a-h and 13a-e) were synthesized and evaluated for their ALK5 inhibitory and antimicrobial activity. The structures were confirmed by their 1H NMR, 13C NMR, and HRMS spectra. All the synthesized compounds were screened against Gram-positive strains, Gram-negative strains, and fungi.

Results: Among the synthesized compounds, compound 12h showed the highest activity (IC50 = 0.416 μM) against ALK5 kinase. Compound 12h exhibited a good selectivity index of > 24 against p38α MAP kinase and was 6.0-fold more selective than the clinical candidate, compound 2 (LY-2157299). Nearly all the compounds displayed high selectivity toward both Gram-positive and Gram-negative bacteria. They also showed similar or 2.0-fold greater antifungal activity (minimum inhibitory concentration [MIC] = 0.5 µg/mL) compared with the positive control compounds Gatifloxacin (MIC = 0.5 µg/mL) and fluconazole (MIC = 1 µg/mL).

Conclusion: The findings suggest that the synthesized rhodanine compounds have good ALK5 inhibitory activity and can be used for further research and development as potential antifungal drugs.
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http://dx.doi.org/10.2174/1573406417666210628144849DOI Listing
June 2021

The synergy of BET inhibitors with aurora A kinase inhibitors in MYCN-amplified neuroblastoma is heightened with functional TP53.

Neoplasia 2021 06 7;23(6):624-633. Epub 2021 Jun 7.

Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA. Electronic address:

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared to single agents, these combinations cooperated to decrease levels of N-myc. We treated both TP53-wild type and mutant, MYCN-amplified cell lines with the BETi JQ1 and the AURKAi Alisertib. The combination had improved efficacy in the TP53-WT context, notably driving apoptosis in both genetic backgrounds. JQ1+Alisertib combination treatment of a MYCN-amplified, TP53-null or TP53-restored genetically engineered mouse model of NBL prolonged survival better than either single agent. This was most profound with TP53 restored, with marked tumor shrinkage and apoptosis induction in response to combination JQ1+Alisertib. BETi+AURKAi in MYCN-amplified NBL, particularly in the context of functional TP53, provided anti-tumor benefits in preclinical models. This combination should be studied more closely in a pediatric clinical trial.
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http://dx.doi.org/10.1016/j.neo.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192452PMC
June 2021

Bromodomain protein BRD4 directs and sustains CD8 T cell differentiation during infection.

J Exp Med 2021 Aug 26;218(8). Epub 2021 May 26.

Division of Biological Sciences, University of California San Diego, La Jolla, CA.

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule-mediated BET inhibition impaired maintenance of a terminal effector T cell phenotype. BRD4 was also required for terminal differentiation of CD8 T cells in the tumor microenvironment in murine models, which we show has implications for immunotherapies. Taken together, these data reveal an unappreciated requirement for BRD4 in coordinating activity of cis regulatory elements to control CD8 T cell fate and lineage stability.
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http://dx.doi.org/10.1084/jem.20202512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160575PMC
August 2021

Identification of a novel allele HLA-C*03:560N by next-generation sequencing in a hematopoietic stem cell recipient.

HLA 2021 May 24. Epub 2021 May 24.

HLA typing Laboratory, Blood Center of Shaanxi Province, Institute of Xi'an Blood Bank, Xi'an, China.

A frameshift due to a single nucleotide deletion results in a novel null allele, HLA-C*03:560N. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/tan.14329DOI Listing
May 2021

Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence.

Nat Genet 2021 06 10;53(6):881-894. Epub 2021 May 10.

Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA.

Esophageal squamous cell carcinomas (ESCCs) harbor recurrent chromosome 3q amplifications that target the transcription factor SOX2. Beyond its role as an oncogene in ESCC, SOX2 acts in development of the squamous esophagus and maintenance of adult esophageal precursor cells. To compare Sox2 activity in normal and malignant tissue, we developed engineered murine esophageal organoids spanning normal esophagus to Sox2-induced squamous cell carcinoma and mapped Sox2 binding and the epigenetic and transcriptional landscape with evolution from normal to cancer. While oncogenic Sox2 largely maintains actions observed in normal tissue, Sox2 overexpression with p53 and p16 inactivation promotes chromatin remodeling and evolution of the Sox2 cistrome. With Klf5, oncogenic Sox2 acquires new binding sites and enhances activity of oncogenes such as Stat3. Moreover, oncogenic Sox2 activates endogenous retroviruses, inducing expression of double-stranded RNA and dependence on the RNA editing enzyme ADAR1. These data reveal SOX2 functions in ESCC, defining targetable vulnerabilities.
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http://dx.doi.org/10.1038/s41588-021-00859-2DOI Listing
June 2021

Effect of konjac glucomannan/carrageenan-based edible emulsion coatings with camellia oil on quality and shelf-life of chicken meat.

Int J Biol Macromol 2021 Jul 28;183:331-339. Epub 2021 Apr 28.

Anhui Engineering Laboratory for Agro-products Processing, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China. Electronic address:

The quality and safety of chicken meat are prone to deteriorate due to bacteria reproduction and oxidation reaction. In this study, the antimicrobial and antioxidant effects of KGM-KC coatings incorporated camellia oil were evaluated to extend the shelf-life of chicken meat. The result showed that the KGM/KC-CO coating significantly (P < 0.05) decreased weight loss, pH, thiobarbituric acid reactive substance (TBARS), total volatile nitrogen (TVN) and microbial counts when compared to uncoated samples. The obtained results revealed that KGM/KC-based coating incorporated with CO significantly extended the shelf-life of chicken meat by restraining the oxidation of lipid and protein, and retarding the microbial growth. The sensory evaluation showed that the addition of CO did not affect the odor of chicken meat, maintained the overall acceptability of coated samples. The shelf-life of chicken meat was extended up to 10 days using KGM/KC-based coating containing 3.5% CO at refrigeration (4 °C) compared to control samples. These results indicated CO could be used as an active agent to be dispersed in KGM/KC matrix by emulsification method, and the prepared emulsion coating had positive effects on extending the shelf-life of chicken meat.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.165DOI Listing
July 2021

Development of Dimethylisoxazole-Attached Imidazo[1,2-]pyridines as Potent and Selective CBP/P300 Inhibitors.

J Med Chem 2021 05 19;64(9):5787-5801. Epub 2021 Apr 19.

Center for Green Chemistry and Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, Massachusetts 02125, United States.

The use of epigenetic bromodomain inhibitors as anticancer therapeutics has transitioned from targeting bromodomain extraterminal domain (BET) proteins into targeting non-BET bromodomains. The two most relevant non-BET bromodomain oncology targets are cyclic AMP response element-binding protein (CBP) and E1A binding protein P300 (EP300). To explore the growing CBP/EP300 interest, we developed a highly efficient two-step synthetic route for dimethylisoxazole-attached imidazo[1,2-]pyridine scaffold-containing inhibitors. Our efficient two-step reactions enabled high-throughput synthesis of compounds designed by molecular modeling, which together with structure-activity relationship (SAR) studies facilitated an overarching understanding of selective targeting of CBP/EP300 over non-BET bromodomains. This led to the identification of a new potent and selective CBP/EP300 bromodomain inhibitor, UMB298 (compound , CBP IC 72 nM and bromodomain 4, BRD4 IC 5193 nM). The SAR we established is in good agreement with literature-reported CBP inhibitors, such as CBP30, and demonstrates the advantage of utilizing our two-step approach for inhibitor development of other bromodomains.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02232DOI Listing
May 2021

Correlation of prostatic morphological parameters and clinical progression in aging Chinese men with benign prostatic hyperplasia: Results from a cross-sectional study.

Prostate 2021 Jun 16;81(8):478-486. Epub 2021 Apr 16.

Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Our study aimed to investigate the correlation of prostatic morphological parameters and benign prostatic hyperplasia (BPH) clinical progression in aging Chinese men.

Methods: In this retrospective study, a total of 1038 patients were reviewed. Prostatic morphology was measured by transrectal ultrasound (TRUS). Detailed medical history of all candidates was recorded and analyzed after being classified by specific prostatic measurements. Univariate and multivariate logistic regression analyses were used to estimate the correlation between variables.

Results: The cumulative incidence of BPH clinical progression was 63.68% (661/1038) in the study population. Prostate volume (PV), transitional zone volume (TZV), transitional zone index (TZI), and intravesical prostatic protrusion (IPP) were all positively associated with BPH progression (all p < .001). Patients with a PV > 60 ml, TZV > 15 ml, TZI > 0.5, or IPP > 5 mm had a significantly higher possibility of overall BPH clinical progression (adjusted odds ratio (OR): 2.485, 1.678, 1.886, and 1.924, respectively; 95% confidence interval (CI): 1.559-3.960, 1.131-2.489, 1.379-2.579, and 1.357-2.728, correspondingly).

Conclusion: Prostatic morphological parameters are significantly associated with BPH clinical progression. Patients with larger prostatic morphological parameters are more easily prone to clinical progress. As a result, reasonable managements should be timely considered for those patients before clinical progression occurs.
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http://dx.doi.org/10.1002/pros.24128DOI Listing
June 2021

LncRNA NORAD regulates scar hypertrophy via miRNA-26a mediating the regulation of TGFβR1/2.

Adv Clin Exp Med 2021 Apr;30(4):395-403

Department of Burns and Plastic Surgery, Affiliated Hospital of Nantong University, China.

Background: Transforming growth factor-β (TGF-β) pathway presents dysregulation in pathological scarring and mediates hypertrophic scar (HS) formation.

Objectives: The study aims to analyze the potential mechanism of long non-coding RNA NORAD (LncRNA NORAD) and microRNA (miR-26a) regulation of the TGF-β pathway in hypertrophic scar fibroblasts (HSFs).

Material And Methods: Hypertrophic scar tissues were collected and assayed for LncRNA NORAD, miR-26a, transforming growth factor β receptor I (TGF-βR1) and TGF-βR2, with enzyme-linked immunosorbent assay (ELISA) or qualitative polymerase chain reaction (qPCR). LncRNA NORAD interfering plasmids were transfected into HSFs and induced with TGF-β1. Cell Counting Kit-8 (CCK-8) assays were performed to assess HSF proliferation, and flow cytometry to analyze apoptosis and the cell cycle. TGF-βR1, TGF-βR2, Smad2, and p-Smad2 levels were detected using western blot (WB). The related proteins (p21, cyclin D1 and cyclin-dependent kinase 4 (CDK4)) regulating the cell cycle, and apoptosis-related proteins (caspase-3 and Bcl-2) were also detected using WB. The binding sites of miRNA-26a and LncRNA NORAD, TGF-βR2, or UBE3A were predicted using Starbase and confirmed with dual luciferase reporter assay. RNA immunoprecipitation (RIP) was utilized to explore the interplay of miR-26a with its target genes.

Results: LncRNA NORAD is decreased, miR-26a is increased and TGF-β receptors show abnormal expression in scar tissue. LncRNA NORAD knockdown inhibits proliferation of HSF cells induced by TGF-β1 treatment. In addition, cell apoptotic levels are markedly increased and cell numbers in G0/G1 phase are increased. Moreover, the TGF-β/Smad pathway is regulated by decreasing endogenous LncRNA NORAD levels, possibly by affecting the relative levels of TGF-βR1. p21 is notably upregulated, while cyclin D1 and CDK4 are downregulated. Apoptosis-related proteins are significantly affected. LncRNA NORAD may act as a sponge, binding miR-26a and changing its expression. Finally, RIP shows that miR-26a targets the 3'UTRs of TGF-βR2 and UBE3A.

Conclusions: LncRNA NORAD regulates HSF proliferation via miR-26a mediating the regulation of TGF-βR2/R1. LncRNA NORAD/miR-26a could be a potential target for treating HS.
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http://dx.doi.org/10.17219/acem/133482DOI Listing
April 2021

Characteristics and prognostic value of potential dependency genes in clear cell renal cell carcinoma based on a large-scale CRISPR-Cas9 and RNAi screening database DepMap.

Int J Med Sci 2021 11;18(9):2063-2075. Epub 2021 Mar 11.

Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200092, P.R. China.

Background: Large-scale loss-of-function screening database such as Cancer Dependency Map (Depmap) provide abundant resources. Investigation of these potential dependency genes from human cancer cell lines in the real-world patients cohort would evaluate their prognostic value thus facilitate their clinical application and guide drug development.

Methods: A few genes were selected from top clear cell renal cell carcinoma (ccRCC) lineage preferential dependency candidates from Depmap. Their characteristic including expression levels both in normal and tumor tissues and correlations with methylation or copy number, genetic alterations, functional enrichment, immune-associated interactions, prognostic value were evaluated in KIRC cohort from TCGA, GTEx, and multiple other open databases and platforms.

Results: 16 genes were collected from 106 ccRCC preferential candidates and further analyzed including B4GALT4, BCL2L1, CDH2, COPG1, CRB3, FERMT2, GET4, GPX4, HNF1B, ITGAV, MDM2, NFE2L2, PAX8, RUVBL1, TFRC, and TNFSF10. The normalized gene effect scores of these genes varied from different ccRCC cell lines and principal component analysis (PCA) showed their tissue specificity expression profiles. Genetic alteration rates of them were low to moderate (0.7%-13%) in KIRC cohort. CDH2, MDM2, TNFSF10 showed a statistically significant higher level in tumors than normal tissues while PAX8 and FERMT2 were significantly downregulated. Moderate positive or negative correlations were observed in several genes between their expression and relative gene copy number or methylation levels, respectively. Based on the multivariable COX regression model adjusted by critical clinical variables revealed the expression of GET4 (p=0.002, HR=1.023 95%CI 1.009-1.038) and CRB3 (p<0.001, HR=0.969 95%CI 0.960-0.980) were independent predictive factors for overall survival in KIRC cohort.

Conclusions: A dependency gene validated in cell lines didn't directly represent its role in corresponding patients with same histological type and their prognostic value might be determined by multiple factors including dependency driven types, genetic alteration rates and expression levels. GET4 and CRB3 were the independent prognostic factors for ccRCC patients. CRB3 seemed like a potential broad tumor suppressor gene while GET4 might be a ccRCC preferential dependency gene with a ligandable structure.
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http://dx.doi.org/10.7150/ijms.51703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040392PMC
March 2021

Moderate mechanical stress suppresses the IL-1β-induced chondrocyte apoptosis by regulating mitochondrial dynamics.

J Cell Physiol 2021 Apr 6. Epub 2021 Apr 6.

Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Mitochondrial dysfunction contributes to osteoarthritis (OA) onset and progress. Mitochondrial dynamics, coupled with mitophagy, is critical for the maintenance of mitochondrial fitness, involving many cellular processes, such as proliferation and apoptosis. Excessive mechanical stress induces chondrocyte apoptosis; however, the effects of mechanical stress on mitochondrial dynamics remain elusive. In this study, we performed fluorescence staining, flow cytometry, transmission electron microscope, Western blot analysis, and RNA-sequencing to assess the effects of different strength of mechanical stimulation on mitochondrial functions of chondrocyte treated with interleukin-1β (IL-1β). We found that moderate mechanical stress reduced the IL-1β-induced apoptosis by maintaining mitochondrial function and scavenging the reactive oxygen species, while excessive mechanical stress induced strong mitochondrial dysfunction and apoptosis. Moreover, RNAsequencing revealed that mitophagy and mitochondrial dynamics were involved in the regulation of mechanical stress on chondrocyte biology. In addition to the elevated mitophagy, moderate mechanical stress also promoted mitochondrial dynamics by enhancing the expression of MFN1/2 and OPA1 and the translocation of dynamin-related protein 1 from the cytoplasm to the mitochondria. However, an uncoupling of mitochondrial dynamics, characterized by strongly elevated fission, resulted in the unfavorable apoptosis of excessive mechanical stress-stimulated chondrocytes. This study revealed the effects of mechanical stress upon mitochondrial dynamics in chondrocyte.
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http://dx.doi.org/10.1002/jcp.30386DOI Listing
April 2021

Enhanced flavor strength of broth prepared from chicken following short-term frozen storage.

Food Chem 2021 Sep 26;356:129678. Epub 2021 Mar 26.

Anhui Engineering Laboratory for Agro-products Processing, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China.

This study investigated the effect of frozen storage periods (0, 2, 4, 6, or 8 weeks) of raw meat and stewing on the flavor of chicken broth. With the increased storage duration of frozen raw material, the contents of the free amino acids, nucleotides and mineral elements in the broth decreased significantly, especially within the first 4 weeks, and then increased significantly. Meanwhile, the volatile compounds showed the reverse trend. The results from the E-nose, E-tongue and sensory evaluation indicated a progressive difference in overall flavor profiles between the samples. The sensory scores of the meaty and fatty traits reached a maximum as raw chicken meat was stored for 4 weeks at -18 °C, which should be related to the increased contents of aldehydes and 2-pentyl furan. Overall, the limited storage duration of frozen raw meat can enhance the flavor of chicken broth.
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http://dx.doi.org/10.1016/j.foodchem.2021.129678DOI Listing
September 2021

Diagnosis of chronic prostatitis by noninvasive methods in elderly patients with benign prostatic hyperplasia in China.

Andrologia 2021 Jul 2;53(6):e14055. Epub 2021 Apr 2.

Department of Urology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, China.

Chronic prostatitis is hard to be identified in BPH patients in clinical works. This study aimed to diagnose chronic prostatitis in BPH patients by noninvasive methods. BPH patients who received transurethral resection of prostate from January 2014 to July 2015 were enrolled in current study. Patients were received examinations of PSA, sex hormones, inflammatory cytokines, metabolic panel and transrectal ultrasonography. According to histological results, patients were divided into two group of BPH with/without prostatitis. Logistic regression was used to find risk factors of chronic prostatitis. As a result, 181 men with an average age of 72.15 ± 8.41 years were enrolled in this study, including 116 patients with prostatitis and 65 patients without prostatitis. The storage sub-score, PSA and IL-2R were significantly higher in patients with prostatitis than those without prostatitis. Based on logistic regression analysis, the above three parameters were also the risk factors of BPH with prostatitis. The diagnostic model was calculated as: 0.317 × storage sub-score + 0.092 × PSA + 0.003 × IL-2R - 4.296. The AUC was 0.725. Histological prostatitis in BPH patients can be diagnosed by the combination of serum IL-2R, PSA and storage sub-score. Identification of chronic prostatitis in BPH patients could more efficiently alleviate urinary symptoms and reduce the risk of disease progression.
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http://dx.doi.org/10.1111/and.14055DOI Listing
July 2021

Genome-wide association analysis reveals regulation of at-risk loci by DNA methylation in prostate cancer.

Asian J Androl 2021 Sep-Oct;23(5):472-478

Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2-q13.43 and 16q22.2-q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.
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http://dx.doi.org/10.4103/aja.aja_20_21DOI Listing
March 2021

Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma.

Cell Rep 2021 03;34(11):108870

Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address:

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR.
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http://dx.doi.org/10.1016/j.celrep.2021.108870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057695PMC
March 2021

Synthesis and evaluation of the epithelial-to- mesenchymal inhibitory activity of indazole-derived imidazoles as dual ALK5/p38α MAP inhibitors.

Eur J Med Chem 2021 Apr 23;216:113311. Epub 2021 Feb 23.

Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, PR China. Electronic address:

Drugs of targeting both activin receptor-like kinase 5 (ALK5) and p38α have therapeutic advantages, making them attractive treatment options for tumors. Two series of 4-(1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazoles 13a-g and 4-(1-methyl-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazoles 20a-g were synthesized and evaluated for ALK5 and p38α mitogen-activated protein kinase inhibitory activity. The most potent compound, 13c (J-1090), inhibited ALK5- and p38α-mediated phosphorylation with half-maximal inhibitor concentrations of 0.004 μM and 0.004 μM, respectively, in the enzymatic assay. In this study, the effectiveness of 13c in transforming growth factor (TGF-β)-exposed U87MG cells was investigated using western blotting, immunofluorescence assays, cell migration assay, invasion assay, and RT-PCR analysis. 13c inhibited the protein expression of Slug and the protein and RNA expression of the mesenchymal-related proteins N-cadherin and vimentin. Furthermore, 13c markedly suppressed TGF-β-induced epithelial-to-mesenchymal transition (EMT), migration, and invasion in U87MG cells. These results suggest that 13c is a novel inhibitor of ALK5 with potential utility in the treatment of human glioma.
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http://dx.doi.org/10.1016/j.ejmech.2021.113311DOI Listing
April 2021

Early urinary continence recovery following retzius-sparing robotic-assistant radical prostatectomy with suprapubic catheter: a short-term follow-up outcome.

World J Urol 2021 Sep 27;39(9):3251-3257. Epub 2021 Feb 27.

Department of Urology, Xiangya Hospital of Central South University, Changsha, China.

Objective: To evaluate the recovery of early urinary continence in patients with prostate cancer using a suprapubic catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy.

Patients And Methods: From January 2018 to January 2019, 223 patients diagnosed with prostate cancer who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy in Diakonie Klinikum Stuttgart were involved in our study. From January 2018 to June 2018, patients (112 cases) only had an indwelling urinary catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy, while from July 2018 to January 2019, patients (111 cases) were offered an extra suprapubic catheter during operation. The recovery of early urinary continence of patients was mainly investigated one month later.

Results: The overall early urinary continence rate was 81.61%. Patients with suprapubic catheter had better urinary control results, compared to patients with only indwelling urinary catheter (87.39% vs 75.89%, p = 0.027). In addition, International Prostate Symptom Score and irritative subscore in patients with good urinary control were significantly lower than that in patients with urinary incontinence. Suprapubic catheter insertion (OR 0.395; 95% CI 0.190-0.821) and advanced pathological tumor stage (T3a-T4) (OR 2.061; 95% CI 1.008-4.217) were two independent influencing factors for early urinary continence recovery in patients who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy through multivariate logistic regression analysis.

Conclusion: Suprapubic catheter insertion may be helpful for early urinary continence recovery in patients with Retzius-sparing Robotic-assistant laparoscopic prostatectomy. Advanced pathological tumor stage (T3a-T4) before Retzius-sparing robotic-assistant laparoscopic prostatectomy might be associated with poor urinary control.
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http://dx.doi.org/10.1007/s00345-021-03643-3DOI Listing
September 2021
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