Publications by authors named "Jie Ji"

197 Publications

Identification of Key Candidate Genes Involved in the Progression of Idiopathic Pulmonary Fibrosis.

Molecules 2021 Feb 20;26(4). Epub 2021 Feb 20.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Hankou Road 22, Nanjing 210093, China.

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein-protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.
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http://dx.doi.org/10.3390/molecules26041123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924352PMC
February 2021

The "Six-and-Twelve" Score for Recurrent HCC Patients Receiving TACE: Does it Still Work?

Cardiovasc Intervent Radiol 2021 Mar 2. Epub 2021 Mar 2.

Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.

Background: A new prognostic model, the "six-and-twelve" (SAT) score, was suggested to be effective in selecting ideal transarterial chemoembolization (TACE) candidates from treatment naïve hepatocellular carcinoma (HCC) patients. However, whether the SAT score could also be applied in recurrent HCC patients with prior curative-intent treatments remains unknown. We aimed to validate and compare SAT focussing on these patients.

Methods: From January 2014 to May 2019, 121 unresectable HCC patients with recurrence in Barcelona Clinic Liver Cancer (BCLC) A/B receiving TACE were enrolled. Survival distribution was evaluated by the Kaplan-Meier method compared by the log-rank test. Discriminatory ability was compared with the concordance index (C-index) to rank six prognostic systems (SAT, Four-and-seven, HAP, mHAP, mHAP2, mHAP3). The area under the curve (AUC) was performed to assess the mortality prediction at 1, 2, and 3 years.

Results: In recurrent HCC patients receiving TACE, SAT had better performances in survival distribution. Due to the highest C-index, SAT was deemed the first ranking prognostic score. In terms of mortality prediction at 1, 2 and 3 years, SAT had the best mortality prediction at 2 and 3 years and mHAP3 had the best mortality prediction at 1 year.

Conclusions: Among the six prognostic systems analysed in ideal TACE patients with recurrences after curative-intent treatments, SAT was proven to be superior to other systems, suggesting that it could also be used in these patients.
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http://dx.doi.org/10.1007/s00270-021-02791-8DOI Listing
March 2021

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR- Activation.

PPAR Res 2021 1;2021:6658944. Epub 2021 Feb 1.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-, which is associated with the phosphorylation of AMPK.
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http://dx.doi.org/10.1155/2021/6658944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870311PMC
February 2021

Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-1/Smad3 and p38/PPAR Pathways.

PPAR Res 2021 28;2021:6651839. Epub 2021 Jan 28.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Objective: The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice.

Methods: Carbon tetrachloride (CCl) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver fibrosis. Sixty-six male C57 mice were randomly divided into eight groups, including the vehicle group, CCl group, CCl+L-apigenin (20 mg/kg) group, CCl+H-apigenin (40 mg/kg) group, sham group, BDL group, BDL+L-apigenin(20 mg/kg) group, and BDL+H-apigenin(40 mg/kg) group. Serum liver enzymes (ALT and AST), proteins associated with autophagy, and indicators linked with the TGF-1/Smad3 and p38/PPAR pathways were detected using qRT-PCR, immunohistochemical staining, and western blotting.

Results: Our findings confirmed that apigenin could decrease the levels of ALT and AST, suppress the generation of ECM, inhibit the activation of HSCs, regulate the balance of MMP2 and TIMP1, reduce the expression of autophagy-linked protein, and restrain the TGF-1/Smad3 and p38/PPAR pathways.

Conclusion: Apigenin could alleviate liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-1/Smad3 and p38/PPAR pathways.
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http://dx.doi.org/10.1155/2021/6651839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861947PMC
January 2021

Co-delivery of siPTPN13 and siNOX4 (myo)fibroblast-targeting polymeric micelles for idiopathic pulmonary fibrosis therapy.

Theranostics 2021 9;11(7):3244-3261. Epub 2021 Jan 9.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China.

(Myo)fibroblasts are the ultimate effector cells responsible for the production of collagen within alveolar structures, a core phenomenon in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Although (myo)fibroblast-targeted therapy holds great promise for suppressing the progression of IPF, its development is hindered by the limited drug delivery efficacy to (myo)fibroblasts and the vicious circle of (myo)fibroblast activation and evasion of apoptosis. Here, a dual small interfering RNA (siRNA)-loaded delivery system of polymeric micelles is developed to suppress the development of pulmonary fibrosis via a two-arm mechanism. The micelles are endowed with (myo)fibroblast-targeting ability by modifying the Fab' fragment of the anti-platelet-derived growth factor receptor-α (PDGFRα) antibody onto their surface. Two different sequences of siRNA targeting protein tyrosine phosphatase-N13 (PTPN13, a promoter of the resistance of (myo)fibroblasts to Fas-induced apoptosis) and NADPH oxidase-4 (NOX4, a key regulator for (myo)fibroblast differentiation and activation) are loaded into micelles to inhibit the formation of fibroblastic foci. We demonstrate that Fab'-conjugated dual siRNA-micelles exhibit higher affinity to (myo)fibroblasts in fibrotic lung tissue. This Fab'-conjugated dual siRNA-micelle can achieve remarkable antifibrotic effects on the formation of fibroblastic foci by, on the one hand, suppressing (myo)fibroblast activation via siRNA-induced knockdown of NOX4 and, on the other hand, sensitizing (myo)fibroblasts to Fas-induced apoptosis by siRNA-mediated PTPN13 silencing. In addition, this (myo)fibroblast-targeting siRNA-loaded micelle did not induce significant damage to major organs, and no histopathological abnormities were observed in murine models. The (myo)fibroblast-targeting dual siRNA-loaded micelles offer a potential strategy with promising prospects in molecular-targeted fibrosis therapy.
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http://dx.doi.org/10.7150/thno.54217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847691PMC
January 2021

NLRP3 inflammasome activation in alveolar epithelial cells promotes myofibroblast differentiation of lung-resident mesenchymal stem cells during pulmonary fibrogenesis.

Biochim Biophys Acta Mol Basis Dis 2021 May 27;1867(5):166077. Epub 2021 Jan 27.

Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China; State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is a lethal and agnogenic interstitial lung disease, which has limited therapeutic options. Recently, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome has been demonstrated as an important contributor to various fibrotic diseases following its persistent activation. However, the role of NLRP3 inflammasome in pulmonary fibrogenesis still needs to be further clarified. Here, we found that the activation of the NLRP3 inflammasome was raised in fibrotic lungs. In addition, the NLRP3 inflammasome was found to be activated in alveolar epithelial cells (AECs) in the lung tissue of both IPF patients and pulmonary fibrosis mouse models. Further research revealed that epithelial cells, following activation of the NLRP3 inflammasome, could induce the myofibroblast differentiation of lung-resident mesenchymal stem cells (LR-MSCs). In addition, inhibiting the activation of the NLRP3 inflammasome in epithelial cells promoted the expression of dickkopf-1 (DKK1), a secreted Wnt antagonist. DKK1 was capable of suppressing the profibrogenic differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis. In conclusion, this study not only provides a further in-depth understanding of the pathogenesis of pulmonary fibrosis, but also reveals a potential therapeutic strategy for disorders associated with pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.bbadis.2021.166077DOI Listing
May 2021

Crosstalk between PPARs and gut microbiota in NAFLD.

Biomed Pharmacother 2021 Apr 20;136:111255. Epub 2021 Jan 20.

Department of Gastroenterology, Shanghai Tenth People'sHospital, Tongji University School of Medicine, Shanghai, 200072, China. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder in both China and worldwide. It ranges from simple steatosis and progresses over time to nonalcoholic steatohepatitis (NASH), advanced liver fibrosis, cirrhosis, or hepatocellular carcinoma(HCC). Furthermore, NAFLD and its complications impose a huge health burden to society. The microbiota is widely connected and plays an active role in human physiology and pathology, and it is a hidden 'organ' in determining the state of the host, in terms of homeostasis, or disease. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptorsuperfamily and can regulate multiple pathways involved in metabolism, and serve as effective targets forthe treatment of many types of metabolic syndromes, including NAFLD. The purpose of this review is to integrate related articles on gut microbiota, PPARs and NAFLD, and present a balanced overview on how the microbiota can possibly influence the development of NAFLD through PPARs.
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http://dx.doi.org/10.1016/j.biopha.2021.111255DOI Listing
April 2021

The transcranial direct current stimulation over prefrontal cortex combined with the cognitive training reduced the cue-induced craving in female individuals with methamphetamine use disorder: A randomized controlled trial.

J Psychiatr Res 2021 02 22;134:102-110. Epub 2020 Dec 22.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wanping Road, Shanghai, 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China. Electronic address:

Background: Craving and cognitive deficits are potential treatment targets for methamphetamine use disorder (MUD). Previous studies implied that transcranial direct current stimulation (tDCS) and cognitive training respectively improve these symptoms, but the combined effect is unknown. In this study, we investigated the combined effects of tDCS over dorsolateral prefrontal cortex (DLPFC) and computerized cognitive addiction therapy (CCAT) on cue-induced craving and cognitive functions among female individuals with MUD.

Methods: Seventy-five patients with MUD were randomly assigned to three groups: CCAT + tDCS group, CCAT + sham tDCS group and the control group. The former two groups received 20 sessions of cognitive training combined 1.5 mA active/sham tDCS over DLPFC (20min/session, 5times/week), while the control group received usual care which includes routine medical care, health education, physical exercises and psychological support related to relapse prevention. The cue-induced craving and cognitive functions were tested at the baseline, the end of 2nd week and 4th week.

Results: The CCAT + tDCS group showed a significant reduction in cue-induced craving after 4-week intervention. Moreover, the craving score of the real CCAT + tDCS group was significantly lower than that of the CCAT + sham tDCS group and that of the control group at the end of 4th week. A significant improvement in accuracy of TWOB task was only observed in the CCAT + tDCS group at the end of 4th week when compared to baseline. Unexpectedly, participants who received CCAT plus active or sham tDCS did not change their discounting, whereas those in the control group performed more impulsively over time.

Conclusions: The study found that the intervention of tDCS over DLPFC combined with CCAT may have potential benefit in improving treatment outcome in patients with MUD. More research is needed to explore the underlying mechanism.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.056DOI Listing
February 2021

The gut microbiome-bile acid axis in hepatocarcinogenesis.

Biomed Pharmacother 2021 Jan 28;133:111036. Epub 2020 Nov 28.

Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, Shanghai 200060, China; Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related deaths globally, with few effective therapeutic options. Bile acids (BAs) are synthesized from cholesterol in the liver and can be modulated by farnesoid X receptor (FXR) and G-protein coupled BA receptor 1 (GPBAR1/TGR5). Alterations in BAs can affect hepatic metabolic homeostasis and contribute to the pathogenesis of liver cancer. Increasing evidence points to the key role of bacterial microbiota in the promotion and development of liver cancer. They are also involved in the regulation of BA synthesis and metabolism. The purpose of this review is to integrate related articles involving gut microbiota, BAs and HCC, and review how the gut microbiota-BA signaling axis can possibly influence the development of HCC.
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http://dx.doi.org/10.1016/j.biopha.2020.111036DOI Listing
January 2021

Alveolar epithelial cell-derived Sonic hedgehog promotes pulmonary fibrosis through OPN-dependent alternative macrophage activation.

FEBS J 2020 Dec 13. Epub 2020 Dec 13.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, China.

The alternative activation of macrophages in the lungs has been considered as a major factor promoting pulmonary fibrogenesis; however, the mechanisms underlying this phenomenon are still elusive. In this study, we investigated the interaction between macrophages and fibrosis-associated alveolar epithelial cells using a bleomycin-induced mouse pulmonary fibrosis model and a coculture system. We demonstrated that fibrosis-promoting macrophages are spatially proximate to alveolar type II (ATII) cells, permissive for paracrine-induced macrophage polarization. Importantly, we revealed that fibrosis-associated ATII cells secrete Sonic hedgehog (Shh), a hedgehog pathway ligand, and that ATII cell-derived Shh promotes the development of pulmonary fibrosis by osteopontin (OPN)-mediated macrophage alternative activation. Mechanistically, Shh promotes the secretion of OPN in macrophages via Shh/Gli signaling cascade. The secreted OPN acts on the surrounding macrophages in an autocrine or paracrine manner and induces macrophage alternative activation through activating the JAK2/STAT3 signaling pathway. Tissue samples from idiopathic pulmonary fibrosis patients confirmed the increased expression of Shh and OPN in ATII cells and macrophages, respectively. Together, our study illustrated an alveolar epithelium-dependent mechanism for macrophage M2 polarization and pulmonary fibrogenesis and suggested that targeting Shh may offer a selective and efficient therapeutic strategy for the development and progression of pulmonary fibrosis.
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http://dx.doi.org/10.1111/febs.15669DOI Listing
December 2020

First Report of Golovinomyces cichoracearum Causing Powdery Mildew on Zinnia elegans in China.

Plant Dis 2020 Dec 8. Epub 2020 Dec 8.

Henan Normal University, 66519, College of Life Sciences, Xinxiang, Henan, China.

Zinnia elegans, common zinnia, is an annual plant with highly ornamental values. It is widely planted in many nurseries, city parks, universities and home gardens in China. From August to October 2020, powdery mildew-like signs and symptoms were observed on leaves of Z. elegans growing on the campus of Henan Normal University, Henan Province, China. White powdery colonies in circular- or irregularly shaped-lesions were abundant on both surfaces of leaves and covered up to 95 % of the leaf area. Any infected leaves were chlorotic, deformed or senescence. More than 70 % of the monitored Z. elegans plants showed these signs and symptoms. Conidiophores (n = 20) were 100 to 200 × 9 to 13 μm and composed of foot cells, followed by straight cells and conidia. Mycelial appressoria were single and nipple-shaped. The oval-shaped conidia (n = 30) were 22 to 36 × 12 to 18 μm, with a length/width ratio of 1.4 to 2.7, and produced germ tubes from the polar ends of the spore. No chasmothecia were found. Based on these morphological characteristics, the pathogen was initially identified morphologically as Golovinomyces cichoracearum (Braun and Cook 2012). Structures of the pathogen were scraped from infected leaves and total genomic DNA was isolated using the method previously described by Zhu et al. (2019). The internal transcribed spacer (ITS) region of rDNA was amplified by PCR using the primers ITS1/ITS4 (White et al. 1990) and the amplicon was sequenced by Invitrogen (Shanghai, China). The sequence for the fungus was deposited into GenBank under Accession No. MW029904 and was 99.83 % identical (595/596 bp) to G. cichoracearum on Symphyotrichum novi-belgii (HM769725)(Mørk et al. 2011). To perform pathogenicity analysis, leaf surfaces of five healthy plants were fixed in a settling tower and then inoculated by blowing fungal conidia from mildew-infested leaves using pressurized air. Five non-inoculated plants served as a control. The inoculated and non-inoculated plants were separately maintained in two growth chambers (humidity, 60 %; light/dark, 16 h/8 h; temperature, 18 ℃). Eleven- to twelve-days post-inoculation, powdery mildew signs were conspicuous on inoculated plants, while control plants remained healthy. Similar results were obtained by conducting two repeated pathogenicity assays. Thus, based on the morphological characteristics and molecular analysis, the pathogen was identified and confirmed as G. cichoracearum. This pathogen has been reported on Z. elegans in India, Israel, Jordan, Korea, Nepal, Sri Lanka, Switzerland, and Turkey (Farr and Rossman 2020). To our best knowledge, this is the first report of G. cichoracearum on Z. elegans in China. The sudden outbreak of powdery mildew caused by G. cichoracearum on Z. elegans may adversely impact the plant health and ornamental value in China. Therefore, the confirmation of G. cichoracearum infecting Z. elegans expands the understanding of this pathogen and provides the fundamental knowledge for future powdery mildew control.
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http://dx.doi.org/10.1094/PDIS-11-20-2333-PDNDOI Listing
December 2020

Contribution of Cation Addition to MnO Nanosheets on Stable Co O Nanowires for Aqueous Zinc-Ion Battery.

Front Chem 2020 23;8:793. Epub 2020 Sep 23.

Hubei Key Laboratory of Ferro and Piezoelectric Materials and Devices, Faculty of Physics and Electronic Science, Hubei University, Wuhan, China.

Zinc-based electrochemistry attracts significant attention for practical energy storage owing to its uniqueness in terms of low cost and high safety. In this work, we propose a 2.0-V high-voltage Zn-MnO battery with core@shell CoO@MnO on carbon cloth as a cathode, an optimized aqueous ZnSO electrolyte with Mn additive, and a Zn metal anode. Benefitting from the architecture engineering of growing CoO nanorods on carbon cloth and subsequently deposited MnO on CoO with a two-step hydrothermal method, the binder-free zinc-ion battery delivers a high power of 2384.7 W kg, a high capacity of 245.6 mAh g at 0.5 A g, and a high energy density of 212.8 Wh kg. It is found that the Mn cations are converted to MnO during electrochemical operations followed by a phase transition into electroactive MnO in our battery system. The charge-storage mechanism of the MnO-based cathode is Zn/Zn and H insertion/extraction. This work shines light on designing multivalent cation-based battery devices with high output voltage, safety, and remarkable electrochemical performances.
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http://dx.doi.org/10.3389/fchem.2020.00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539680PMC
September 2020

First Report of Powdery Mildew Caused by Blumeria graminis f. sp. bromi on Bromus catharticus in China.

Plant Dis 2020 Nov 9. Epub 2020 Nov 9.

Henan Normal University, 66519, College of Life Sciences, Xinxiang, Henan, China.

Bromus catharticus, rescuegrass, is a brome grass that has been cultivated for herbage production, and been widely naturalized in many provinces of China, including Henan province. During April and May 2020, powdery mildew was found on leaves of Br. catharticus on the campus of Henan Normal University, Xinxiang city (35.3°N; 113.9°E), Henan Province, China. Abundant white or grayish irregular or coalesced circular powdery colonies were scattered on the adaxial surface of leaves and 70% of the leaf areas were affected. Some of the infected leaves either were chlorotic or senescent. About 60% of the observed plants showed powdery mildew symptoms. Conidiophores (n = 25) were 32 to 45 μm × 7 to 15 μm and composed of foot cells and conidia (mostly 6 conidia) in chains. Conidia (n = 50) were 25 to 35 μm × 10 to 15 μm, on average 30 × 13 μm, with a length/width ratio of 2.3. Chasmothecia were not found. Based on these morphologic characteristics, the pathogen was initially identified as Blumeria graminis f. sp. bromi (Braun and Cook 2012; Troch et al. 2014). B. graminis mycelia and conidia were collected, and total genomic DNA was extracted (Zhu et al. 2019). The rDNA internal transcribed spacer (ITS) region was amplified with primer pairs ITS1/ITS4. The amplicon was cloned and sequenced. The sequence (574 bp) was deposited into GenBank under Accession No. MT892940. BLASTn analysis revealed that MT892940 was 100% identical to B. graminis f. sp. bromi on Br. catharticus (AB000935, 550 of 550 nucleotides) (Takamatsu et al. 1998). Phylogenetic analysis of MT892940 and ITS of other B. graminis ff. spp. clearly indicated least two phylogenetically distinct clades of B. graminis f. sp. bromi and that MT892940 clustered with the Takamatsu vouchers. Leaf surfaces of five healthy plants were fixed at the base of a settling tower and then inoculated by blowing conidia from diseased leaves using pressurized air. Five non-inoculated plants served as controls. The inoculated and non-inoculated plants were maintained separately in two growth chambers (humidity, 60%; light/dark, 16 h/8 h; temperature, 18℃). Thirteen- to fifteen-days after inoculation, B. graminis signs and symptoms were visible on inoculated leaves, whereas control plants remained asymptomatic. The pathogenicity assays were repeated twice with the same results. The observed signs and symptoms were morphologically identical to those of the originally infected leaves. Accordingly, the causal organism of the powdery mildew was confirmed as B. graminis f. sp. bromi by morphological characteristics and ITS sequence data. B. graminis has been reported on Br. catharticus in the United States (Klingeman et al. 2018), Japan (Inuma et al. 2007) and Argentina (Delhey et al. 2003). To our best knowledge, this is the first report of B. graminis on Br. catharticus in China. Since hybridization of B. graminis ff. spp. is a mechanism of adaptation to new hosts, Br. catharticus may serve as a primary inoculum reservoir of B. graminis to infect other species (Menardo et al. 2016). This report provides fundamental information for the powdery mildew that can be used to develop control management of the disease in Br. catharticus herbage production.
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http://dx.doi.org/10.1094/PDIS-09-20-1983-PDNDOI Listing
November 2020

Gut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2020 29;7:271-288. Epub 2020 Oct 29.

Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, Shanghai 200060, People's Republic of China.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC incidence rate is sixth and mortality is fourth worldwide. However, HCC pathogenesis and molecular mechanisms remain unclear. The incidence of HCC is associated with genetic, environmental, and metabolic factors. The role of gut microbiota in the pathogenesis of HCC has attracted researchers' attention because of anatomical and functional interactions between liver and intestine. Studies have demonstrated the involvement of gut microbiota in the development of HCC and chronic liver diseases, such as alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and liver cirrhosis. Peroxisome proliferator-activated receptors (PPARs) are a group of receptors with diverse biological functions. Natural and synthetic PPAR agonists show potential for treatment of NAFLD, liver fibrosis, and HCC. Recent studies have demonstrated that PPARs take part in gut microbiota inhabitation and adaptation. This manuscript reviews the role of gut microbiota in the development of HCC and precancerous diseases, the role of PPARs in modulation of gut microbiota and HCC, and potential of gut microbiota for HCC diagnosis and treatment.
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http://dx.doi.org/10.2147/JHC.S277870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605923PMC
October 2020

Occurrence of Powdery Mildew Caused by Blumeria graminis f. sp. poae on Poa pratensis in China.

Plant Dis 2020 Nov 3. Epub 2020 Nov 3.

Henan Normal University, 66519, College of Life Sciences, Xinxiang, Henan, China.

Poa pratensis, known as bluegrass, is a perennial grass and one of the best varieties with highly valued pasture and turf grass uses. It is widely grown on golf courses and used for lawns in squares and parks (Luo et al. 2020). During April and May 2020, powdery mildew-like signs and symptoms were observed on leaves of P. pratensis in Muye Park, Xinxiang city (35.3°N; 113.9°E), Henan Province, China. White or grayish powdery masses in spots- or coalesced lesions were abundant on the adaxial surfaces of leaves and covered up to 90 % of the leaf area. Some of the mildew-infested leaves appeared chlorotic or began senescence. Mildew-infested leaves were collected to microscopically observe the morphological characteristics of this pathogen. Conidiophores were composed of foot cells, followed by one or two cells, and conidia. The ellipsoid- shaped conidia (n = 50) were 25 - 36 × 10 - 15 μm (length × width), on average 30 × 13 μm, with a length/width ratio of 2.3. Foot-cells (n = 15) were 30 - 44 μm long and 7 - 15 μm wide. On leaf surfaces, germinated conidia produced a short primary germ tube and then a long secondary germ tube that finally differentiated into a hooked appressorium. Chasmothecia were not found. Based on these morphological characteristics, the pathogen was initially identified as B. graminis f. sp. poae, the known forma specialis (f. sp.) of B. graminis on P. pratensis (Braun and Cook 2012; Troch et al. 2014). Mycelia of the pathogen were scraped from infected leaves and total genomic DNA was isolated using the method described previously (Zhu et al. 2019). The rDNA internal transcribed spacer (ITS) region was amplified applying primer pairs ITS1/ITS4 (White et al. 1990). The amplicon was cloned and sequenced by Invitrogen (Shanghai, China). The obtained sequence for the pathogen was deposited into GenBank under Accession No. MT892956 and was 100 % identical (549/549 bp) to B. graminis on P. pratensis (AB273530) (Inuma et al. 2007). In addition, the phylogenetic analysis clearly showed that the identified fungus and B. graminis f. sp. poae were clustered in the same branch. To perform pathogenicity analysis, leaf surfaces of eight healthy plants were inoculated by dusting fungal conidia from diseased leaves. Eight non-inoculated plants served as a control. The non-inoculated and inoculated plants were separately maintained in two growth chambers (humidity, 60 %; light/dark, 16 h/8 h; temperature, 18 ℃). Twelve to fourteen days after inoculation, B. graminis signs were visible on inoculated leaves, while control plants remained healthy. The pathogenicity assays were repeated twice and showed same results. Therefore, based on the morphological characteristics and molecular analysis, the pathogen was identified and confirmed as B. graminis f. sp. poae. This pathogen has been reported on P. pratensis in Switzerland and Japan (Inuma et al. 2007). This is, to our best knowledge, the first disease note reporting B. graminis on P. pratensis in China. Because the hybridization of B. graminis formae speciales (ff. spp.). allow the pathogens to adapt to new hosts, P. pratensis may serve as a primary inoculum reservoir of B. graminis to threaten other species, including cereal crops (Klingeman et al. 2018; Menardo et al. 2016). In addition, powdery mildew may negatively affect the yield and quality of grasses. Our report expands the knowledge of B. graminis f. sp. poae and provides the fundamental information for future powdery mildew control.
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http://dx.doi.org/10.1094/PDIS-09-20-2051-PDNDOI Listing
November 2020

Low-dose ruxolitinib shows effective in treating myelofibrosis.

Ann Hematol 2021 Jan 20;100(1):135-141. Epub 2020 Oct 20.

Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, #37 GuoXue Xiang Street, 610041, Chengdu, China.

The aim of this study was to investigate the effect of low-dose ruxolitinib (daily dose ≤ 10 mg) for the treatment of myelofibrosis (MF). A retrospective analysis was performed on a total of 88 patients with myeloproliferative neoplasm-associated MF (MPN-MF) who were diagnosed and treated in West China Hospital, Sichuan University, China. A total of 44 MPN-MF patients received a low dose of ruxolitinib (daily dose ≤ 10 mg), while another 44 patients received 10-25 mg twice daily. Low-dose ruxolitinib treatment resulted in slow, but gradual spleen response. Compared with baseline, the mean changes in palpable spleen length in the low- and high-dose groups were -26.9 and -49.0% after 12 weeks of treatment, respectively, and -46.7 and -64.1% after 48 weeks of treatment, respectively. In the low dose group, the median myeloproliferative neoplasm symptom assessment form (MPN-SAF) total symptom score (TSS) decreased by 37.8 and 35.9% at the 12 weeks and 48 weeks after treatment, respectively. No statistical difference was observed in MPN-SAF TSS among different dose groups. After 48 weeks of treatment, bone marrow (BM) fibrosis improved in 43.3% (13/30) of evaluated patients and was stable in 56.7% (17/30) patients. In the low-dose treated group, BM fibrosis improved in 50% patients and was stable in remaining 50%. Low-dose ruxolitinib is effective in treating MF.
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http://dx.doi.org/10.1007/s00277-020-04311-zDOI Listing
January 2021

OsSYL2 , an allele identified by gene-based association, increases style length in rice (Oryza sativa L.).

Plant J 2020 12 30;104(6):1491-1503. Epub 2020 Oct 30.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.

Stigma characteristics are important factors affecting the seed yield of hybrid rice per unit area. Natural variation of stigma characteristics has been reported in rice, but the genetic basis for this variation is largely unknown. We performed a genome-wide association study on three stigma characteristics in six environments using 1.3 million single-nucleotide polymorphism (SNPs) characterized in 353 diverse accessions of Oryza sativa. An abundance of phenotypic variation was present in the three stigma characteristics of these collections. We identified four significant SNPs associated with stigma length, 20 SNPs with style length (SYL), and 17 SNPs with the sum of stigma and style length, which were detected repeatedly in more than four environments. Of these SNPs, 28 were novel. We identified two causal gene loci for SYL, OsSYL3 and OsSYL2; OsSYL3 was co-localized with the grain size gene GS3. The SYL of accessions carrying allele OsSYL3 was significantly longer than that of those carrying allele OsSYL3 . We also demonstrated that the outcrossing rate of female parents carrying allele OsSYL2 increased by 5.71% compared with that of the isogenic line carrying allele OsSYL2 in an F hybrid seed production field. The allele frequencies of OsSYL3 and OsSYL2 decreased gradually with an increase in latitude in the Northern Hemisphere. Our results should facilitate the improvement in stigma characteristics of parents of hybrid rice.
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http://dx.doi.org/10.1111/tpj.15013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821000PMC
December 2020

Photodynamic therapy with acitretin for treatment of penile verrucous carcinoma.

Photodiagnosis Photodyn Ther 2021 Mar 3;33:102047. Epub 2020 Oct 3.

Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Guang Zhou Rd 300, Nanjing, Jiangsu, 210029, China. Electronic address:

Penile verrucous carcinoma exhibits a high potential for recurrence. Traditional treatment for penile verrucous carcinoma is radical surgery. Extensive resection generally leads to the loss of the patient's sexual function and limits the tolerance for additional additional surgical resection. Herein, we present a case of penile verrucous carcinoma, who achieved complete remission after 3 sessions of PDT and 6 months Acitretin. There was no recurrence at 12 months of follow-up. This case suggests that photodynamic therapy combined with acitretin is a treatment option for penile verrucous carcinoma.
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http://dx.doi.org/10.1016/j.pdpdt.2020.102047DOI Listing
March 2021

A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction.

Cereb Cortex 2021 Jan;31(1):547-561

Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA.

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach-connectome-wide similarity-we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.
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http://dx.doi.org/10.1093/cercor/bhaa242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947178PMC
January 2021

Nintedanib in Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation.

Chest 2020 Sep;158(3):e89-e91

Department of Hematology, Sichuan University West China Hospital, Chengdu, China. Electronic address:

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (allo-HCT) usually confers poor prognosis and high mortality. Currently, therapeutic options are limited. Here we report an 18-year-old man with acute myeloid leukemia developed BOS after allo-HCT and responded poorly to inhaled corticosteroids and short-acting β-agonist, azithromycin, montelukast, and immunosuppressants. Then he started nintedanib treatment, and the symptoms of nonproductive cough and dyspnea were alleviated gradually. His pulmonary function test revealed increased FEV compared to baseline.
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http://dx.doi.org/10.1016/j.chest.2020.05.557DOI Listing
September 2020

Serum galectin-3 as a biomarker for screening, early diagnosis, prognosis and therapeutic effect evaluation of pancreatic cancer.

J Cell Mol Med 2020 10 4;24(19):11583-11591. Epub 2020 Sep 4.

Department of Gastroenterology, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Galectin-3 plays an important role in cell-cell adhesion, macrophage activation, angiogenesis, metastasis and apoptosis and is overexpressed in pancreatic cancer. We explored the importance of galectin-3 in the screening, early diagnosis, prognosis and therapeutic effect evaluation of pancreatic cancer. A time-resolved fluorescence immunoassay was performed to detect serum galectin-3 level. Serum samples were collected from healthy controls and patients with pancreatic cancer before and after different treatments, and the relationships between galectin-3 level and clinical parameters were analysed. Among the healthy controls, one individual with an abnormally high concentration of galectin-3 (9.85 μg/L) was diagnosed with pancreatic cancer. Compared to the pre-operative level, galectin-3 concentration significantly decreased in patients with radical excision 1 month after surgery (P < .05), but showed no obvious change in patients who underwent palliative resection. Additionally, among patients with radical excision, carcinoma recurrence rate was significantly higher in those with increased or unchanged galectin-3 level. Retrospective analysis revealed the extraordinarily high value and high specificity of galectin-3 for predicting 3-year survival (P < .001). Thus, galectin-3 may serve as a potential biomarker for the screening and early diagnosis of pancreatic cancer and as an independent prognostic indicator in patients with pancreatic cancer.
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http://dx.doi.org/10.1111/jcmm.15775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576229PMC
October 2020

The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer.

Mol Biol Rep 2020 Aug 5;47(8):6091-6103. Epub 2020 Aug 5.

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.

Cervical cancer is the leading cause of cancer-related death among women worldwide. Identifying an effective treatment with fewer side effects is imperative, because all of the current treatments have unique disadvantages. Aldo-keto reductase family 1 member B1 (AKR1B1) is highly expressed in various cancers and is associated with tumor development, but has not been studied in cervical cancer. In the current study, we used CRISPR/Cas9 technology to establish a stable HeLa cell line with AKR1B1 knockout. In vitro, AKR1B1 knockout inhibited the proliferation, migration and invasion of HeLa cells, providing evidence that AKR1B1 is an innovative therapeutic target. Notably, the clinically used epalrestat, an inhibitor of aldose reductases, including AKR1B1, had the same effect as AKR1B1 knockout on HeLa cells. This result suggests that epalrestat could be used in the clinical treatment of cervical cancer, a prospect that undoubtedly requires further research. Moreover, aiming to determine the underlying regulatory mechanism of AKR1B1, we screened a series of differentially regulated genes (DEGs) by RNA sequencing and verified selected DEGs by quantitative RT-PCR. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed a correlation between AKR1B1 and cancer. In summary, epalrestat inhibits the progression of cervical cancer by inhibiting AKR1B1, and thus may be a new drug for the clinical treatment of cervical cancer.
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http://dx.doi.org/10.1007/s11033-020-05685-zDOI Listing
August 2020

A new house dust mite-driven and mast cell-activated model of asthma in the guinea pig.

Clin Exp Allergy 2020 10 5;50(10):1184-1195. Epub 2020 Aug 5.

Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Stockholm, Sweden.

Background: Animal models are extensively used to study underlying mechanisms in asthma. Guinea pigs share anatomical, pharmacological and physiological features with human airways and may enable the development of a pre-clinical in vivo model that closely resembles asthma.

Objectives: To develop an asthma model in guinea pigs using the allergen house dust mite (HDM).

Methods: Guinea pigs were intranasally sensitized to HDM which was followed by HDM challenges once weekly for five weeks. Antigen-induced bronchoconstriction (AIB) was evaluated as alterations in R (Newtonian resistance), G (tissue damping) and H (tissue elastance) at the first challenge with forced oscillation technique (FOT), and changes in respiratory pattern upon each HDM challenge were assessed as enhanced pause (Penh) using whole-body plethysmography. Airway responsiveness to methacholine was measured one day after the last challenge by FOT. Inflammatory cells and cytokines were quantified in bronchoalveolar lavage fluid, and HDM-specific immunoglobulins were measured in serum by ELISA. Airway pathology was evaluated by conventional histology.

Results: The first HDM challenge after the sensitization generated a marked increase in R and G, which was abolished by pharmacological inhibition of histamine, leukotrienes and prostanoids. Repeated weekly challenges of HDM caused increase of Penh and a marked increase in airway hyperresponsiveness for all three lung parameters (R , G and H) and eosinophilia. Levels of IgE, IgG , IgG and IL-13 were elevated in HDM-treated guinea pigs. HDM exposure induced infiltration of inflammatory cells into the airways with a pronounced increase of mast cells. Subepithelial collagen deposition, airway wall thickness and goblet cell hyperplasia were induced by repeated HDM challenge.

Conclusion And Clinical Relevance: Repeated intranasal HDM administration induces mast cell activation and hyperplasia together with an asthma-like pathophysiology in guinea pigs. This model may be suitable for mechanistic investigations of asthma, including evaluation of the role of mast cells.
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http://dx.doi.org/10.1111/cea.13713DOI Listing
October 2020

Transcriptomics Inform Hierarchical Neuroimaging Features Relevant for Psychosis Spectrum Symptoms.

Biol Psychiatry 2020 08;88(3):212-214

Department of Psychiatry, Yale University, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.

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http://dx.doi.org/10.1016/j.biopsych.2020.05.016DOI Listing
August 2020

Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma.

J Exp Clin Cancer Res 2020 Jul 6;39(1):126. Epub 2020 Jul 6.

Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China.

Liver cancer has become the sixth most diagnosed cancer and the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is responsible for up to 75-85% of primary liver cancers, and sorafenib is the first targeted drug for advanced HCC treatment. However, sorafenib resistance is common because of the resultant enhancement of aerobic glycolysis and other molecular mechanisms. Aerobic glycolysis was firstly found in HCC, acts as a hallmark of liver cancer and is responsible for the regulation of proliferation, immune evasion, invasion, metastasis, angiogenesis, and drug resistance in HCC. The three rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), and pyruvate kinases type M2 (PKM2) play an important role in the regulation of aerobic glycolysis in HCC and can be regulated by many mechanisms, such as the AMPK, PI3K/Akt pathway, HIF-1α, c-Myc and noncoding RNAs. Because of the importance of aerobic glycolysis in the progression of HCC, targeting key factors in its pathway such as the inhibition of HK2, PFK or PKM2, represent potential new therapeutic approaches for the treatment of HCC.
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http://dx.doi.org/10.1186/s13046-020-01629-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336654PMC
July 2020

Identification of prognostic risk factors for pancreatic cancer using bioinformatics analysis.

PeerJ 2020 15;8:e9301. Epub 2020 Jun 15.

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.

Background: Pancreatic cancer is one of the most common malignant cancers worldwide. Currently, the pathogenesis of pancreatic cancer remains unclear; thus, it is necessary to explore its precise molecular mechanisms.

Methods: To identify candidate genes involved in the tumorigenesis and proliferation of pancreatic cancer, the microarray datasets GSE32676, GSE15471 and GSE71989 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between Pancreatic ductal adenocarcinoma (PDAC) and nonmalignant samples were screened by GEO2R. The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool was used to obtain a synthetic set of functional annotation information for the DEGs. A PPI network of the DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and a combination of more than 0.4 was considered statistically significant for the PPI. Subsequently, we visualized the PPI network using Cytoscape. Functional module analysis was then performed using Molecular Complex Detection (MCODE). Genes with a degree ≥10 were chosen as hub genes, and pathways of the hub genes were visualized using ClueGO and CluePedia. Additionally, GenCLiP 2.0 was used to explore interactions of hub genes. The Literature Mining Gene Networks module was applied to explore the cocitation of hub genes. The Cytoscape plugin iRegulon was employed to analyze transcription factors regulating the hub genes. Furthermore, the expression levels of the 13 hub genes in pancreatic cancer tissues and normal samples were validated using the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Moreover, overall survival and disease-free survival analyses according to the expression of hub genes were performed using Kaplan-Meier curve analysis in the cBioPortal online platform. The relationship between expression level and tumor grade was analyzed using the online database Oncomine. Lastly, the eight snap-frozen tumorous and adjacent noncancerous adjacent tissues of pancreatic cancer patients used to detect the CDK1 and CEP55 protein levels by western blot.

Conclusions: Altogether, the DEGs and hub genes identified in this work can help uncover the molecular mechanisms underlying the tumorigenesis of pancreatic cancer and provide potential targets for the diagnosis and treatment of this disease.
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http://dx.doi.org/10.7717/peerj.9301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301898PMC
June 2020

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase.

Clin Cancer Res 2020 08 27;26(16):4216-4224. Epub 2020 May 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China.

Purpose: Mantle-cell lymphoma (MCL) is an incurable mature B-cell neoplasm with high initial response rates followed almost invariably by relapse. Prognosis for patients following relapse is poor, and treatment choices are limited. We evaluated the efficacy and safety of zanubrutinib, an investigational selective Bruton's tyrosine kinase (BTK) inhibitor.

Patients And Methods: Patients with relapsed/refractory MCL were enrolled in this ongoing phase II, single-arm, open-label study, and treated with oral zanubrutinib 160 mg twice daily. The primary endpoint is overall response rate (ORR) assessed by an independent review committee (per Lugano 2014 classification); secondary endpoints include duration of response (DOR), time to response, progression-free survival (PFS), and safety.

Results: Eighty-six patients (median age, 60.5 years) were enrolled after a median of 2 prior lines of therapy, received ≥1 dose of the study drug, and were evaluable for safety and efficacy. After a median follow-up of 18.4 months, 72 (84%) patients achieved an objective response, with 59 (68.6%) achieving a complete response (CR). Median DOR and PFS were 19.5 and 22.1 months, respectively; 12-month event-free estimates for DOR and PFS are 78% and 76%, respectively. Most common grade ≥3 adverse events (AE) were neutropenia (19.8%) and lung infection/pneumonia (9.3%). Three patients experienced major bleeding events, and there were no reports of atrial fibrillation. Eight (9.3%) patients discontinued zanubrutinib for AEs.

Conclusions: These results demonstrate high and durable ORR and CR rates in patients with relapsed/refractory MCL. Zanubrutinib was generally well tolerated; grade ≥3 BTK inhibitor-associated toxicities (hemorrhage, rash, hypertension, diarrhea, atrial fibrillation) were uncommon.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3703DOI Listing
August 2020

Vitamin D regulates cell viability, migration and proliferation by suppressing galectin-3 (Gal-3) gene in ovarian cancer cells.

J Biosci 2020 ;45

Department of Pathology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Vitamin D deficiency is identified as a risk factor for the occurrence and recurrence of ovarian cancer. Galectin-3 (Gal-3) participates in many physiological and pathological processes. In present study, serum vitamin D level was detected using chemiluminescence enzyme immunoassay. Gal-3 expression was examined using real-time polymerase chain reaction (PCR), Western blot and immunocytochemistry analysis. SKOV3 cells viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, the migration of SKOV3 cells was detected using transwell assay, and the proliferation of SKOV3 cells was measured by 3H-thymidine incorporation (H-TdR). Our study demonstrated that vitamin D levels were lower in 40 ovarian cancer patients: vitamin D deficiency is closely related to the pathogenesis of ovarian cancer. Treatment with vitamin D reduced the migration and proliferation of ovarian cancer cells. Gal-3 was overexpressed in ovarian cancer, which could induce the viability, migration and proliferation ability of ovarian cancer cells, and these effects were abrogated by vitamin D downregulating the expression of Gal-3 gene. Therefore, our results support that vitamin D may suppress Gal-3-induced viability, migration and proliferation ability of ovarian cancer cells, which suggests that the use of vitamin D may have beneficial effects in preventing and treating ovarian cancer.
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March 2021

Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC-1α pathway.

Br J Pharmacol 2020 08 27;177(16):3760-3777. Epub 2020 Jun 27.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background And Purpose: Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The present study aimed to elucidate the protective effect of astaxanthin against NAFLD and its underlying mechanism.

Experimental Approach: Mice were fed either a high fat or chow diet, with or without astaxanthin, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of astaxanthin for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria was also evaluated.

Key Results: The results indicated that astaxanthin attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Astaxanthin up-regulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of astaxanthin on ameliorating NAFLD.

Conclusion And Implications: Astaxanthin attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by up-regulating FGF21/PGC-1α pathway. Our results suggest that astaxanthin may become a promising drug to treat or relieve NAFLD.
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http://dx.doi.org/10.1111/bph.15099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393201PMC
August 2020

In utero exposure to DBP stimulates release of GnRH by increasing the secretion of PGE2 in the astrocytes of the hypothalamus in the offspring mice.

Ecotoxicol Environ Saf 2020 Jul 7;198:110698. Epub 2020 May 7.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address:

Di-n-butyl phthalate (DBP), the most commonly used plasticizer and typical endocrine disrupting chemicals (EDCs), has shown its characteristics of causing reproductive and developmental toxicity in males, while the neuroendocrine toxicity induced by DBP exposure in utero and the mechanism beneath still remain unclear. Here, the pregnant mice were treated with corn oil (control) or DBP at three different doses by oral gavage during gestational days (GD) 12.5-21.5. The results showed that in utero exposure to DBP induced a significant increase of gonadotropin releasing hormone (GnRH) content in serum, as well as activation and proliferation of astrocytes in the hypothalamus of offspring male mice on postnatal day (PND) 22. However, in in vitro study, mono-n-butyl phthalate (MBP), the metabolite of DBP, could not increase the release of GnRH after GnRH neurons were exposed to MBP. Further studies identified that MBP-mediated activation and proliferation of astrocytes resulted in increased secretion of prostaglandin E2 (PGE2), which might be responsible for the increased release of GnRH from GnRH neurons. This study highlights the neuroendocrine toxicity of current plasticizer DBP exposure, laying the foundation for identifying potential molecular targets for related diseases.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110698DOI Listing
July 2020