DSpace Collection:http://hdl.handle.net/10722/2115452024-03-28T13:02:00Z2024-03-28T13:02:00ZAssociation of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhageLee, TCLeung, WCHo, CChiu, MWLeung, IYWong, YKLiu, RKCSum, CHLui, DTCheung, RLeung, GKKChan, KHTeo, KCLau, GKKhttp://hdl.handle.net/10722/3416842024-03-20T06:58:16Z2024-03-01T00:00:00ZTitle: Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage
Authors: Lee, TC; Leung, WC; Ho, C; Chiu, MW; Leung, IY; Wong, YK; Liu, RKC; Sum, CH; Lui, DT; Cheung, R; Leung, GKK; Chan, KH; Teo, KC; Lau, GKK
Abstract: <h3>Background:</h3><p>Recent intensive LDL-C lowering trials, including FOURIER, ODYSSEY OUTCOMES, and TST trials, have mostly refuted the concern surrounding statin use, low-density lipoprotein cholesterol (LDL-C) lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than ten times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking.</p><h3>Aims:</h3><p>We aim to investigate the association between LDL-C levels and statin use with ICH risk amongst ICH survivors, and to determine whether the risk differed with patients’ characteristics, especially ICH etiology.</p><h3>Methods:</h3><p>Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston Criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ≥1.8mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models.</p><h3>Results:</h3><p>In 502 ICH survivors (mean age 64.2±13.5 years, mean follow-up LDL-C 2.2±0.6mmol/L, 28% with LDL-C <1.8mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9±2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio [AHR] 1.07, 95% confidence interval [CI] 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8mmol/L (AHR 1.99, 95% CI 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR 2.52, 95% CI 1.06-5.99) and non-statin users (AHR 2.91, 95% CI 1.08-7.86).</p><h3>Conclusion:</h3><p>The association between post-ICH LDL-C <1.8mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.</p>2024-03-01T00:00:00ZEnhancing the efficacy of vaccinia-based oncolytic virotherapy by inhibiting CXCR2-mediated MDSC traffickingTan, ZhiwuChiu, Mei SumYue, MingKwok, Hau YeeTse, Man HoWen, YangChen, BohaoYang, DaweiZhou, DongyanSong, You-QiangMan, KwanChen, Zhiweihttp://hdl.handle.net/10722/3409872024-03-11T10:48:50Z2023-12-08T00:00:00ZTitle: Enhancing the efficacy of vaccinia-based oncolytic virotherapy by inhibiting CXCR2-mediated MDSC trafficking
Authors: Tan, Zhiwu; Chiu, Mei Sum; Yue, Ming; Kwok, Hau Yee; Tse, Man Ho; Wen, Yang; Chen, Bohao; Yang, Dawei; Zhou, Dongyan; Song, You-Qiang; Man, Kwan; Chen, Zhiwei
Abstract: <p>Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid derived suppressor cells (MDSC) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in-situ vaccinia virotherapy recruited primarily polymorphonuclear MDSC (PMN-MDSC) into the TME where they exhibited strong suppression of cytotoxic T lymphocytes (CTL) in a reactive oxygen species (ROS)-dependent way. Single-cell RNA sequencing analysis confirmed the suppressive profile of PMN-MDSC at the transcriptomic level and identified CXCR2 as a therapeutic target expressed on PMN-MDSC. Abrogating PMN-MDSC trafficking by CXCR2-specific small molecule inhibitor during the vaccinia virotherapy exhibited enhanced antitumor efficacy in three syngeneic cancer models, through increasing CD8+/MDSC ratios in the TME, activating CTL and skewing suppressive TME into an antitumor environment. Our results warrant clinical development of CXCR2 inhibitor in combination with oncolytic virotherapy.</p>2023-12-08T00:00:00ZMetal-coding assisted serological multi-omics profiling deciphers the role of selenium in COVID-19 immunityZhou, YingYuan, ShuofengXiao, FanLi, HongyanYe, ZiweiCheng, TianfanLuo, CuitingTang, KaimingCai, JianpiaoSitu, JianwenSridhar, SiddharthChu, Wing-MingTam, Anthony RaymondChu, HinChe, Chi-MingJin, LijianHung, Ivan Fan-NgaiLu, LiweiChan, Jasper Fuk-WooSun, Hongzhehttp://hdl.handle.net/10722/3409192024-03-11T10:48:18Z2023-09-18T00:00:00ZTitle: Metal-coding assisted serological multi-omics profiling deciphers the role of selenium in COVID-19 immunity
Authors: Zhou, Ying; Yuan, Shuofeng; Xiao, Fan; Li, Hongyan; Ye, Ziwei; Cheng, Tianfan; Luo, Cuiting; Tang, Kaiming; Cai, Jianpiao; Situ, Jianwen; Sridhar, Siddharth; Chu, Wing-Ming; Tam, Anthony Raymond; Chu, Hin; Che, Chi-Ming; Jin, Lijian; Hung, Ivan Fan-Ngai; Lu, Liwei; Chan, Jasper Fuk-Woo; Sun, Hongzhe
Abstract: <p>Uncovering how host metal(loid)s mediate the immune response against invading pathogens is critical for better understanding the pathogenesis mechanism of infectious disease. Clinical data show that imbalance of host metal(loid)s is closely associated with the severity and mortality of COVID-19. However, it remains elusive how metal(loid)s, which are essential elements for all forms of life and closely associated with multiple diseases if dysregulated, are involved in COVID-19 pathophysiology and immunopathology. Herein, we built up a metal-coding assisted multiplexed serological metallome and immunoproteome profiling system to characterize the links of metallome with COVID-19 pathogenesis and immunity. We found distinct metallome features in COVID-19 patients compared with non-infected control subjects, which may serve as a biomarker for disease diagnosis. Moreover, we generated the first correlation network between the host metallome and immunity mediators, and unbiasedly uncovered a strong association of selenium with interleukin-10 (IL-10). Supplementation of selenium to immune cells resulted in enhanced IL-10 expression in B cells and reduced induction of proinflammatory cytokines in B and CD4<small><sup>+</sup></small> T cells. The selenium-enhanced IL-10 production in B cells was confirmed to be attributable to the activation of ERK and Akt pathways. We further validated our cellular data in SARS-CoV-2-infected K18-hACE2 mice, and found that selenium supplementation alleviated SARS-CoV-2-induced lung damage characterized by decreased alveolar inflammatory infiltrates through restoration of virus-repressed selenoproteins to alleviate oxidative stress. Our approach can be readily extended to other diseases to understand how the host defends against invading pathogens through regulation of metallome.<br></p>2023-09-18T00:00:00ZThe m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemiaWeng, HengyouHuang, FengYu, ZhaojinChen, ZhenhuaPrince, EmilyKang, YalinZhou, KerenLi, WeiHu, JiachengFu, ChenAziz, TursunjanLi, HongzhiLi, JingwenYang, YingHan, LiZhang, SuboMa, YuelongSun, MingliWu, HuizheZhang, ZhengWunderlich, MarkRobinson, SeanBraas, DanielHoeve, Johanna tenZhang, BinMarcucci, GuidoMulloy, James CZhou, KedaTao, Hong-FangDeng, XiaolanHorne, DavidWei, MinjieHuang, HuilinChen, Jianjunhttp://hdl.handle.net/10722/3408812024-03-11T10:48:00Z2022-12-12T00:00:00ZTitle: The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia
Authors: Weng, Hengyou; Huang, Feng; Yu, Zhaojin; Chen, Zhenhua; Prince, Emily; Kang, Yalin; Zhou, Keren; Li, Wei; Hu, Jiacheng; Fu, Chen; Aziz, Tursunjan; Li, Hongzhi; Li, Jingwen; Yang, Ying; Han, Li; Zhang, Subo; Ma, Yuelong; Sun, Mingli; Wu, Huizhe; Zhang, Zheng; Wunderlich, Mark; Robinson, Sean; Braas, Daniel; Hoeve, Johanna ten; Zhang, Bin; Marcucci, Guido; Mulloy, James C; Zhou, Keda; Tao, Hong-Fang; Deng, Xiaolan; Horne, David; Wei, Minjie; Huang, Huilin; Chen, Jianjun
Abstract: <p>N6 -Methyladenosine (m6 A) modification and its modulators play critical roles and show promise as therapeutic targets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recently reported as an m6 A binding protein that enhances mRNA stability and translation. However, its function in AML remains largely elusive. Here we report the oncogenic role and the therapeutic targeting of IGF2BP2 in AML. High expression of IGF2BP2 is observed in AML and associates with unfavorable prognosis. IGF2BP2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating expression of critical targets (e.g., MYC, GPT2, and SLC1A5) in the glutamine metabolism pathways in an m6 A-dependent manner. Inhibiting IGF2BP2 with our recently identified small-molecule compound (CWI1-2) shows promising anti-leukemia effects in vitro and in vivo. Collectively, our results reveal a role of IGF2BP2 and m6 A modification in amino acid metabolism and highlight the potential of targeting IGF2BP2 as a promising therapeutic strategy in AML.<br></p>2022-12-12T00:00:00Z