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2. One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study

Author

Roshanov, Pavel S., Chan, Matthew T. V., Borges, Flavia K., Conen, David, Wang, C. Y., Xavier, Denis, Berwanger, Otavio, Marcucci, Maura, Sessler, Daniel I., Szczeklik, Wojciech, Spence, Jessica, Alonso-Coello, Pablo, Fernández, Carmen, Pearse, Rupert M., Malaga, German, Garg, Amit X., Srinathan, Sadeesh K., Jacka, Michael J., Tandon, Vikas, McGillion, Michael, Popova, Ekaterine, Sigamani, Alben, Abraham, Valsa, Biccard, Bruce M., Villar, Juan Carlos, Chow, Clara K., Polanczyk, Carísi A., Tiboni, Maria, Whitlock, Richard, Ackland, Gareth L., Panju, Mohamed, Lamy, André, Sapsford, Robert, Williams, Colin, Wu, William Ka Kei, Cortés, Olga L., MacNeil, S. Danielle, Patel, Ameen, Belley-Côté, Emilie P., Ofori, Sandra, McIntyre, William F., Leong, Darryl P., Heels-Ansdell, Diane, Gregus, Krysten, and Devereaux, P. J.

Published
2024
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3. Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice

Author

Li, Qing, Chan, Hung, Liu, Wei-Xin, Liu, Chang-An, Zhou, Yunfei, Huang, Dan, Wang, Xueliang, Li, Xiaoxing, Xie, Chuan, Liu, Wing Ying-Zhi, Wang, Xian-Song, Ng, Siu Kin, Gou, Hongyan, Zhao, Liu-Yang, Fong, Winnie, Jiang, Lanping, Lin, Yufeng, Zhao, Guijun, Bai, Feihu, Liu, Xiaodong, Chen, Huarong, Zhang, Lin, Wong, Sunny Hei, Chan, Matthew Tak Vai, Wu, William Ka Kei, and Yu, Jun

Published
2023
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5. SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1

Author

Sun, Xiao, Liu, Yingzhi, Huang, Ziheng, Xu, Wenye, Hu, Wei, Yi, Lina, Liu, Zhe, Chan, Hung, Zeng, Judeng, Liu, Xiaodong, Chen, Huarong, Yu, Jun, Chan, Francis Ka Leung, Ng, Siew Chien, Wong, Sunny Hei, Wang, Maggie Haitian, Gin, Tony, Joynt, Gavin Matthew, Hui, David Shu Cheong, Zou, Xuan, Shu, Yuelong, Cheng, Christopher Hon Ki, Fang, Shisong, Luo, Huanle, Lu, Jing, Chan, Matthew Tak Vai, Zhang, Lin, and Wu, William Ka Kei

Published
2022
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10. Lactone-to-Lactam Editing Alters the Pharmacology of Bilobalide

Author

Jiang, Xiaoding, He, Xu, Wong, Jonathan, Scheeff, Stephan, Hau, Sam Chun-Kit, Wong, Tak Hin, Qin, Yao, Fan, Chi Hang, Ma, Bowen, Chung, Ngai Lam, Huang, Junzhe, Zhao, Jiajia, Yan, Yu, Xiao, Min, Song, Xueqin, Hui, Tony K. C., Zuo, Zhong, Wu, William Ka-Kei, Ko, Ho, Chow, Kim Hei-Man, and Ng, Billy Wai-Lung

Abstract

Precise transformations of natural products (NPs) can fine-tune their physicochemical properties while preserving inherently complex and evolutionarily optimized parent scaffolds. Here, we report an unprecedented lactone-to-lactam transformation on bilobalide, thus improving its stability and paving the way for biological exploration of previously inaccessible chemical space that is highly representative of the parent structure. This late-stage molecular editing of bilobalide enables facile access to a unique library of lactam analogues with altered pharmacology. Through phenotypic screening, we identify BB10as a hit compound with unexpected inhibition of ferroptotic cell death. We further reveal that BB10suppresses ferroptosis by restoring the expression of glutathione peroxidase 4 (GPX4) in brain cells. This study highlights that even subtle changes on NP scaffolds can confer new pharmacological properties, inspiring the exploration of simple yet critical transformations on complex NPs.

Published
2024
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12. One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study

Author

Roshanov, Pavel S., primary, Chan, Matthew T. V., additional, Borges, Flavia K., additional, Conen, David, additional, Wang, C. Y., additional, Xavier, Denis, additional, Berwanger, Otavio, additional, Marcucci, Maura, additional, Sessler, Daniel I., additional, Szczeklik, Wojciech, additional, Spence, Jessica, additional, Alonso-Coello, Pablo, additional, Fernández, Carmen, additional, Pearse, Rupert M., additional, Malaga, German, additional, Garg, Amit X., additional, Srinathan, Sadeesh K., additional, Jacka, Michael J., additional, Tandon, Vikas, additional, McGillion, Michael, additional, Popova, Ekaterine, additional, Sigamani, Alben, additional, Abraham, Valsa, additional, Biccard, Bruce M., additional, Villar, Juan Carlos, additional, Chow, Clara K., additional, Polanczyk, Carísi A., additional, Tiboni, Maria, additional, Whitlock, Richard, additional, Ackland, Gareth L., additional, Panju, Mohamed, additional, Lamy, André, additional, Sapsford, Robert, additional, Williams, Colin, additional, Wu, William Ka Kei, additional, Cortés, Olga L., additional, MacNeil, S. Danielle, additional, Patel, Ameen, additional, Belley-Côté, Emilie P., additional, Ofori, Sandra, additional, McIntyre, William F., additional, Leong, Darryl P., additional, Heels-Ansdell, Diane, additional, Gregus, Krysten, additional, and Devereaux, P. J., additional

Published
2023
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13. Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes

Author

Nakatsu, Geicho, Zhou, Haokui, Wu, William Ka Kei, Wong, Sunny Hei, Coker, Olabisi Oluwabukola, Dai, Zhenwei, Li, Xiangchun, Szeto, Chun-Ho, Sugimura, Naoki, Lam, Thomas Yuen-Tung, Yu, Allen Chi-Shing, Wang, Xiansong, Chen, Zigui, Wong, Martin Chi-Sang, Ng, Siew Chien, Chan, Matthew Tak Vai, Chan, Paul Kay Sheung, Chan, Francis Ka Leung, Sung, Joseph Jao-Yiu, and Yu, Jun

Published
2018
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15. Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer

Author

Xia, Xiaoxuan, Wu, William Ka Kei, Wong, Sunny Hei, Liu, Dabin, Kwong, Thomas Ngai Yeung, Nakatsu, Geicho, Yan, Pearlly S., Chuang, Yu-Ming, Chan, Michael Wing-Yan, Coker, Olabisi Oluwabukola, Chen, Zigui, Yeoh, Yun Kit, Zhao, Liuyang, Wang, Xiansong, Cheng, Wing Yin, Chan, Matthew Tak Vai, Chan, Paul Kay Sheung, Sung, Joseph Jao Yiu, Wang, Maggie Haitian, and Yu, Jun

Published
2020
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17. Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery :An International Randomized Controlled Trial.

Author

Marcucci, Maura, Painter, Thomas TW, Conen, David, Lomivorotov, Vladimir, Sessler, Daniel I, Chan, Matthew T V, Borges, Flavia K, Leslie, Kate, Duceppe, Emmanuelle, Martínez-Zapata, María José, Wang, Chew Yin, Xavier, Denis, Ofori, Sandra N, Wang, Michael Ke, Efremov, Sergey, Landoni, Giovanni, Kleinlugtenbelt, Ydo YV, Szczeklik, Wojciech, Schmartz, Denis, Garg, Amit X, Short, Timothy TG, Wittmann, Maria, Meyhoff, Christian Sylvest, Amir, Mohammed, Torres, David, Patel, Ameen, Ruetzler, Kurt, Parlow, Joel JL, Tandon, Vikas, Fleischmann, Edith, Polanczyk, Carísi Anne, Lamy, Andre, Jayaram, Raja, Astrakov, Sergey SV, Wu, William Ka Kei, Cheong, Chao Chia, Ayad, Sabry, Kirov, Mikhail M.Y., de Nadal, Miriam, Likhvantsev, Valery VV, Paniagua, Pilar, Aguado, Hector HJ, Maheshwari, Kamal, Whitlock, Richard RP, McGillion, Michael MH, Vincent, Jessica, Copland, Ingrid, Balasubramanian, Kumar, Biccard, Bruce BM, Srinathan, Sadeesh, Ismoilov, Samandar, Pettit, Shirley, Stillo, David, Kurz, Andrea, Belley-Côté, Emilie EP, Spence, Jessica, McIntyre, William WF, Bangdiwala, Shrikant SI, Guyatt, Gordon, Yusuf, Salim, Devereaux, P J, POISE-3 Trial Investigators and Study Groups, Marcucci, Maura, Painter, Thomas TW, Conen, David, Lomivorotov, Vladimir, Sessler, Daniel I, Chan, Matthew T V, Borges, Flavia K, Leslie, Kate, Duceppe, Emmanuelle, Martínez-Zapata, María José, Wang, Chew Yin, Xavier, Denis, Ofori, Sandra N, Wang, Michael Ke, Efremov, Sergey, Landoni, Giovanni, Kleinlugtenbelt, Ydo YV, Szczeklik, Wojciech, Schmartz, Denis, Garg, Amit X, Short, Timothy TG, Wittmann, Maria, Meyhoff, Christian Sylvest, Amir, Mohammed, Torres, David, Patel, Ameen, Ruetzler, Kurt, Parlow, Joel JL, Tandon, Vikas, Fleischmann, Edith, Polanczyk, Carísi Anne, Lamy, Andre, Jayaram, Raja, Astrakov, Sergey SV, Wu, William Ka Kei, Cheong, Chao Chia, Ayad, Sabry, Kirov, Mikhail M.Y., de Nadal, Miriam, Likhvantsev, Valery VV, Paniagua, Pilar, Aguado, Hector HJ, Maheshwari, Kamal, Whitlock, Richard RP, McGillion, Michael MH, Vincent, Jessica, Copland, Ingrid, Balasubramanian, Kumar, Biccard, Bruce BM, Srinathan, Sadeesh, Ismoilov, Samandar, Pettit, Shirley, Stillo, David, Kurz, Andrea, Belley-Côté, Emilie EP, Spence, Jessica, McIntyre, William WF, Bangdiwala, Shrikant SI, Guyatt, Gordon, Yusuf, Salim, Devereaux, P J, and POISE-3 Trial Investigators and Study Groups

Abstract

Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

28. Dihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer

Author

Wang, Lin, Hu, Tao, Shen, Jing, Zhang, Lin, Chan, Ruby Lok-Yi, Lu, Lan, Li, Mingxing, Cho, Chi Hin, and Wu, William. Ka Kei

Subjects
Colon cancer -- Analysis -- Care and treatment, Sage -- Health aspects -- Research, Apoptosis -- Analysis, Biological sciences, Health, Science and technology
Abstract

Background: Dihydrotanshinone I (DHTS) was previously reported to exhibit the most potent anti-cancer activity among several tanshinones in colon cancer cells. Its cytotoxic action was reactive oxygen species (ROS) dependent but p53 independent. Purpose: To further study the anti-cancer activity of DHTS and its molecular mechanisms of action in colon cancer both in vitro and in vivo. Methods: Caspase activity was detected by fluorescence assay. Apoptosis was detected by flow cytometry and TUNEL assay. Protein levels were analyzed by western blotting. Knockdown of target gene was achieved by siRNA transfection. Formation of LC3B puncta and activation of caspase-3 were detected by confocal fluorescence microscope. In vivo anti-colon cancer activity of DHTS was observed in xenograft tumors in NOD/SCID mice. Results: Anti-colon cancer activity of DHTS by inducing apoptosis and autophagy was observed both in vitro and in vivo. Mitochondria mediated caspase dependent pathway was essential in DHTS-induced cytotoxicity. The apoptosis induced by DHTS was suppressed by knockdown of apoptosis inducing factor (AIF), inhibition of caspase-3/9 but was increased after knockdown of caspase-2. Meantime, knockdown of caspase-2, pretreatment with Z-VAD-fmk or NAC (N-Acety-L-Cysteine) efficiently inhibited the autophagy induced by DHTS. A crosstalk between cytochrome c and AIF was also reported. Conclusion: DHTS-induced caspase and ROS dependent apoptosis and autophagy were mediated by mitochondria in colon cancer. DHTS could be a promising leading compound for the development of anti-tumor agent or be developed as an adjuvant drug for colon cancer therapy. Keywords: Dihydrotanshinone I Apoptosis Autophagy Caspase Mitochondria Colon cancer, Introduction The search for effective regimens with minimal adverse effects for the treatment of colon cancer remains the top priority of cancer research. So far, a number of traditional Chinese [...]

Published
2015
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29. Single-Hit Inactivation Drove Tumor Suppressor Genes Out of the X Chromosome during Evolution

Author

Wang, Xiansong, primary, Hu, Wei, additional, Li, Xiangchun, additional, Huang, Dan, additional, Li, Qing, additional, Chan, Hung, additional, Zeng, Judeng, additional, Xie, Chuan, additional, Chen, Huarong, additional, Liu, Xiaodong, additional, Gin, Tony, additional, Wang, Maggie Haitian, additional, Cheng, Alfred Sze Lok, additional, Kang, Wei, additional, To, Ka-Fai, additional, Plewczynski, Dariusz, additional, Zhang, Qingpeng, additional, Chen, Xiaoting, additional, Chan, Danny Cheuk Wing, additional, Ko, Ho, additional, Wong, Sunny Hei, additional, Yu, Jun, additional, Chan, Matthew Tak Vai, additional, Zhang, Lin, additional, and Wu, William Ka Kei, additional

Published
2022
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33. Additional file 20 of Altered gut metabolites and microbiota interactions are implicated in colorectal carcinogenesis and can be non-invasive diagnostic biomarkers

Author

Coker, Olabisi Oluwabukola, Liu, Changan, Wu, William Ka Kei, Wong, Sunny Hei, Jia, Wei, Sung, Joseph J. Y., and Yu, Jun

Abstract

Additional file 19: Figure S14. Heatmap of correlations between disease associated metabolites. The correlation strengths were measured by Spearman���s rank correlation coefficient. Only correlation coefficients with p > 0.05 were shown on the heatmap. The size of the circles are proportional to the correlation strength.

Published
2022
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38. Vitamin D3and carbamazepine protect againstClostridioides difficileinfection in mice by restoring macrophage lysosome acidification

Author

Chan, Hung, primary, Li, Qing, additional, Wang, Xiansong, additional, Liu, Wing Yingzhi, additional, Hu, Wei, additional, Zeng, Judeng, additional, Xie, Chuan, additional, Kwong, Thomas Ngai Yeung, additional, Ho, Idy Hiu Ting, additional, Liu, Xiaodong, additional, Chen, Huarong, additional, Yu, Jun, additional, Ko, Ho, additional, Chan, Raphael Chiu Yeung, additional, Ip, Margaret, additional, Gin, Tony, additional, Cheng, Alfred Sze Lok, additional, Zhang, Lin, additional, Chan, Matthew Tak Vai, additional, Wong, Sunny Hei, additional, and Wu, William Ka Kei, additional

Published
2022
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46. Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID‐19–associated Guillain‐Barré syndrome

Author

Li, Zheng, primary, Huang, Ziheng, additional, Li, Xingye, additional, Huang, Cheng, additional, Shen, Jianxiong, additional, Li, Shugang, additional, Zhang, Lin, additional, Wong, Sunny H., additional, Chan, Matthew T. V., additional, and Wu, William Ka Kei, additional

Published
2021
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47. Additional file 1 of Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer

Author

Xiaoxuan Xia, Wu, William Ka Kei, Wong, Sunny Hei, Dabin Liu, Kwong, Thomas Ngai Yeung, Geicho Nakatsu, Pearlly S. Yan, Chuang, Yu-Ming, Chan, Michael Wing-Yan, Olabisi Oluwabukola Coker, Zigui Chen, Yeoh, Yun Kit, Liuyang Zhao, Xiansong Wang, Cheng, Wing Yin, Chan, Matthew Tak Vai, Chan, Paul Kay Sheung, Sung, Joseph Jao Yiu, Wang, Maggie Haitian, and Yu, Jun

Abstract

Additional file 1: Figure S1. Differential genome-wide coverage of MBDCap sequence reads. Data was arcsine-square-root-transformed to help visualize low coverage regions. Rows and columns represent chromosomal segments and sample methylation profiles, respectively. Row heights are normalized relative chromosome-wide CpG density. Boxes highlight significant tissue phenotypes that had the highest mean sequence coverage for a genomic feature within a chromosome. TPM, transcripts per million. Circles, P < 0.05; Stars, P < 0.01. P-values were from Kruskal-Wallis tests. Figure S2. Differentially methylated regions (DMRs) in colorectal carcinogenesis. Of the 1,059 representative DMRs identified, 465 (43.9%) were annotated with HGNCs; this subset of segments was assigned to promoter regions (96 or 20.6%) in which CpG islands were present (48 or 50%). Rows and columns represent genomic segments and sample DMR profiles, respectively. Figure S3. Heatmap of bacteria abundances in phenotype groups. From left to right the bacteria abundances are displayed in groups of normal, adenoma adjacent (AN), adenoma, CRC AN, and CRC. From top to bottom the bacteria are ranked by the fold-change between CRC and CRC AN samples. The bacteria shown are the ones with differential abundance between any two phenotype groups (P < 0.2). Figure S4. Induction of prostaglandin E2 biosynthetic pathway by H. hathewayi. Expression of Pla2g4c and Cox2 in colonic epithelium of mice gavaged with or without H. hathewayi was quantified by RT-qPCR. Expression levels were compared using t-test. *, P < 0.05; ** P < 0.01 significantly different between the indicated groups. Supplementary Table 1. Top bacteria-methylation interactions of C. hathewayi and F. nuleatum with tumor suppressor genes. Supplementary Table 2. The positive significant (ZINB p-value ≤ 0.05) interactions of MLH1, APC, PTEN, P16, CDX1 and CDX2 with bacteria.

Published
2020
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48. Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19

Author

Fang, Shisong, primary, Zhang, Lin, additional, Liu, Yingzhi, additional, Xu, Wenye, additional, Wu, Weihua, additional, Huang, Ziheng, additional, Wang, Xin, additional, Liu, Hui, additional, Sun, Ying, additional, Zhang, Renli, additional, Peng, Bo, additional, Liu, Xiaodong, additional, Sun, Xiao, additional, Yu, Jun, additional, Chan, Francis Ka Leung, additional, Ng, Siew Chien, additional, Wong, Sunny Hei, additional, Wang, Maggie Hai Tian, additional, Gin, Tony, additional, Joynt, Gavin Matthew, additional, Hui, David Shu Cheong, additional, Feng, Tiejian, additional, Wu, William Ka Kei, additional, Chan, Matthew Tak Vai, additional, Zou, Xuan, additional, and Xia, Junjie, additional

Published
2021
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49. Vitamin D3and carbamazepine protect against Clostridioides difficileinfection in mice by restoring macrophage lysosome acidification

Author

Chan, Hung, Li, Qing, Wang, Xiansong, Liu, Wing Yingzhi, Hu, Wei, Zeng, Judeng, Xie, Chuan, Kwong, Thomas Ngai Yeung, Ho, Idy Hiu Ting, Liu, Xiaodong, Chen, Huarong, Yu, Jun, Ko, Ho, Chan, Raphael Chiu Yeung, Ip, Margaret, Gin, Tony, Cheng, Alfred Sze Lok, Zhang, Lin, Chan, Matthew Tak Vai, Wong, Sunny Hei, and Wu, William Ka Kei

Abstract

ABSTRACTClostridioides difficileinfection (CDI) is a common cause of nosocomial diarrhea. TcdB is a major C. difficileexotoxin that activates macrophages to promote inflammation and epithelial damage. Lysosome impairment is a known trigger for inflammation. Herein, we hypothesize that TcdB could impair macrophage lysosomal function to mediate inflammation during CDI. Effects of TcdB on lysosomal function and the downstream pro-inflammatory SQSTM1/p62-NFKB (nuclear factor kappa B) signaling were assessed in cultured macrophages and in a murine CDI model. Protective effects of two lysosome activators (i.e., vitamin D3and carbamazepine) were assessed. Results showed that TcdB inhibited CTNNB1/β-catenin activity to downregulate MITF (melanocyte inducing transcription factor) and its direct target genes encoding components of lysosomal membrane vacuolar-type ATPase, thereby suppressing lysosome acidification in macrophages. The resulting lysosomal dysfunction then impaired autophagic flux and activated SQSTM1-NFKB signaling to drive the expression of IL1B/IL-1β (interleukin 1 beta), IL8 and CXCL2 (chemokine (C-X-C motif) ligand 2). Restoring MITF function by enforced MITF expression or restoring lysosome acidification with 1α,25-dihydroxyvitamin D3or carbamazepine suppressed pro-inflammatory cytokine expression in vitro. In mice, gavage with TcdB-hyperproducing C. difficileor injection of TcdB into ligated colon segments caused prominent MITF downregulation in macrophages. Vitamin D3and carbamazepine lessened TcdB-induced lysosomal dysfunction, inflammation and histological damage. In conclusion, TcdB inhibits the CTNNB1-MITF axis to suppress lysosome acidification and activates the downstream SQSTM1-NFKB signaling in macrophages during CDI. Vitamin D3and carbamazepine protect against CDI by restoring MITF expression and lysosomal function in mice.Abbreviations:ATP6V0B: ATPase H+ transporting V0 subunit b; ATP6V0C: ATPase H+ transporting V0 subunit c; ATP6V0E1: ATPase H+ transporting V0 subunit e1; ATP6V1H: ATPase H+ transporting V1 subunit H; CBZ: carbamazepine; CDI: C. difficileinfection; CXCL: chemokine C-X-X motif ligand; IL: interleukin; LAMP1: lysosomal-associated membrane protein 1; LC3: microtubule-associated protein 1 light chain 3; LEF: lymphoid enhancer binding factor 1; MITF: melanocyte inducing transcription factor; NFKB: nuclear factor kappa B; PMA: phorbol 12-myristate 13-acetate; TcdA: Clostridial toxin A; TcdB: Clostridial toxin B; TFE3: transcription factor E3; TFEB: transcription factor EB.

Published
2022
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