Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3
J Mol Cell Biol. 2024 Apr 5:mjae015. doi: 10.1093/jmcb/mjae015. Online ahead of print.ABSTRACTThe recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingl...
Source: Mol Biol Cell - April 5, 2024 Category: Molecular Biology Authors: Miao Wang Xiao-Wei Li Sen-Chao Yuan Jie Pan Zeng-Lin Guo Li-Ming Sun Shao-Zhen Jiang Ming Zhao Wen Xue Hong Cai Lin Gu Dan Luo Ling Chen Xue-Qing Zhou Qiu-Ying Han Jin Li Tao Zhou Tian Xia Tao Li Source Type: research
Autophagic-lysosomal damage induced by swainsonine is protected by trehalose through activation of TFEB-regulated pathway in renal tubular epithelial cells
In this study, we investigate the mechanism of protective effects of trehalose using renal tubular epithelial cells. The results showed that SW induced an increase in the expression level of microtubule-associated protein light chain 3-II and p62 proteins and a decrease in the expression level of ATPase H+ transporting V1 Subunit A, Cathepsin B, Cathepsin D, lysosome-associated membrane protein 2 and TFEB proteins in renal tubular epithelial cells in a time and dose-dependent manner suggesting TFEB-regulated lysosomal pathway is adversely affected by SW. Conversely, treatment with trehalose, a known activator of TFEB promo...
Source: Chemico-Biological Interactions - April 5, 2024 Category: Molecular Biology Authors: Shuhang Zhang Hai Yin Yiqingqing Zhang Yanli Zhu Xueyao Zhu Wenting Zhu Lihui Tang Yiling Liu Kexin Wu Baoyu Zhao Yanan Tian Hao Lu Source Type: research
Targeted mutagenesis of negatively charged amino acids outlining the substrate translocation path within the human organic cation transporter 3
Biochem Pharmacol. 2024 Apr 3:116188. doi: 10.1016/j.bcp.2024.116188. Online ahead of print.ABSTRACTRecently published cryo-EM structures of human organic cation transporters of the SLC22 family revealed seven, sequentially arranged glutamic and aspartic acid residues, which may be relevant for interactions with positively charged substrates. We analyzed the functional consequences of removing those negative charges by creating D155N, E232Q, D382N, E390Q, E451Q, E459Q, and D478N mutants of OCT3. E232Q, E459Q, and D478N resulted in a lack of localization in the outer cell membrane and no relevant uptake activity. However, D...
Source: Biochemical Pharmacology - April 5, 2024 Category: Drugs & Pharmacology Authors: Kyra-Elisa Maria Redeker Sophie Schr öder Christof D ücker J ürgen Brockmöller Lukas Gebauer Source Type: research
Oral bacteria accelerate pancreatic cancer development in mice
Conclusion
Taken together, our findings demonstrate a causal role for P. gingivalis in pancreatic cancer development in mice. (Source: Gut)
Source: Gut - April 5, 2024 Category: Gastroenterology Authors: Saba, E., Farhat, M., Daoud, A., Khashan, A., Forkush, E., Menahem, N. H., Makkawi, H., Pandi, K., Angabo, S., Kawasaki, H., Plaschkes, I., Parnas, O., Zamir, G., Atlan, K., Elkin, M., Katz, L., Nussbaum, G. Tags: Gut Pancreas Source Type: research
N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis
This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracell...
Source: European Journal of Pharmacology - April 4, 2024 Category: Drugs & Pharmacology Authors: Wan-Li Duan Ya-Ping Ma Xue-Jie Wang Chang-Sheng Ma Bo Han Zhi-Mei Sheng Hao Dong Li-Ying Zhang P Andy Li Bao-Gang Zhang Mao-Tao He Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
Targeting NKA α1 to treat Parkinson's disease through inhibition of mitophagy-dependent ferroptosis
In conclusion, this study establishes NKAα1 as a key regulator of ferroptosis and mitophagy, identifying its DR-region as a promising therapeutic target for PD.PMID:38574977 | DOI:10.1016/j.freeradbiomed.2024.04.002 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 4, 2024 Category: Biology Authors: Xiaoyan Zhang Guanghong Li Hanbin Chen Xiao-Wei Nie Jin-Song Bian Source Type: research
Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis
This study unraveled novel targets to revitalize the salivary secretion function in SS patients.PMID:38574973 | DOI:10.1016/j.freeradbiomed.2024.04.003 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 4, 2024 Category: Biology Authors: Jiannan Zhou Janak L Pathak Lihong Wu Bo Chen Tingting Cao Wei Wei Xiaodan Wu Guiping Chen Nobumoto Watanabe Xiaomeng Li Jiang Li Source Type: research
N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis
This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracell...
Source: European Journal of Pharmacology - April 4, 2024 Category: Drugs & Pharmacology Authors: Wan-Li Duan Ya-Ping Ma Xue-Jie Wang Chang-Sheng Ma Bo Han Zhi-Mei Sheng Hao Dong Li-Ying Zhang P Andy Li Bao-Gang Zhang Mao-Tao He Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia
Haematologica. 2024 Apr 4. doi: 10.3324/haematol.2023.282952. Online ahead of print.ABSTRACTResistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patien...
Source: Haematologica - April 4, 2024 Category: Hematology Authors: Chi Zhang Kathy Yuen Yee Chan Wing Hei Ng John Tak Kit Cheung Qiwei Sun Han Wang Po Yee Chung Frankie Wai Tsoi Cheng Alex Wing Kwan Leung Xiao-Bing Zhang Po Yi Lee Siu Ping Fok Guanglan Lin Ellen Ngar Yun Poon Jian-Hua Feng Yan-Lai Tang Xue-Qun Luo Li-Bin Source Type: research
