- |||||||||| Journal: Upregulation of complement proteins in lung cancer cells mediates tumor progression. (Pubmed Central) - Jan 24, 2023
Silencing complement regulatory proteins also inhibited tumor growth, with different regulatory proteins acting in a cell-specific manner. Based on these data we propose that localized induction of complement in cancer cells is a common feature of lung tumors that promotes tumor progression, with induction of complement regulatory proteins protecting cells from complement mediated-cell killing.
- |||||||||| Journal: Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation. (Pubmed Central) - Aug 10, 2022
Hemopexin exposed a protective function of factor I activity in vitro, but only when it was present before the addition of heme. In conclusion, we present a mechanistic explanation of how heme promotes uncontrolled complement alternative pathway amplification by interfering with the regulatory capacity of factor I. Reduced levels of hemopexin and hemopexin-factor I complexes during an acute hemolytic crisis is a risk factor for heme-mediated factor I inhibition.
- |||||||||| Review, Journal: Complement Activation and Regulation in Preeclampsia and HELLP Syndrome. (Pubmed Central) - Mar 9, 2022
Taken together, existing data link preeclampsia and HELLP syndrome with increased activation of the terminal complement pathway which, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and HELLP syndrome, but this strategy warrants further evaluation in clinical trials.
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Journal, CAR T-Cell Therapy, PD(L)-1 Biomarker, IO biomarker: APDL1-CART cells exhibit strong PD-L1-specific activity against leukemia cells. (Pubmed Central) - Jul 22, 2021 Whereas large tumors developed in mice inoculated with PDL1-CA46 cells alone or together with control T cells, no tumor formation was detected in xenografts containing aPDL1-CART cells. Our data suggest that immune checkpoint-targeted CAR-T cells may be useful for controlling and eradicating immune-refractory hematological malignancies.
- |||||||||| Preclinical, Journal: Expression and Function of C1orf132 Long-Noncoding RNA in Breast Cancer Cell Lines and Tissues. (Pubmed Central) - Jul 18, 2021
RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.
- |||||||||| Journal: Yak milk-derived exosome alleviates lipopolysaccharide-induced intestinal inflammation by inhibiting PI3K/AKT/C3 pathway activation. (Pubmed Central) - Jul 15, 2021
Our findings demonstrated an important relationship between yak and cow milk exosomes and intestinal inflammation, facilitating further understanding of the mechanisms of inflammation-driven epithelial homeostasis. Interestingly, compared with cow milk exosomes, yak milk exosomes activated the PI3K/AKT/C3 signaling pathway more to lower the incidence and severity of intestine inflammation, which might represent a potential innovative therapeutic option for intestinal inflammation.
- |||||||||| Review, Journal: Complement's favorite organelle - mitochondria? (Pubmed Central) - Jul 7, 2021
Among cell compartments, mitochondria appear to have built a particularly early and strong relationship with the complosome and extracellularly active complement - not surprising in view of the strong impact of the complosome on metabolism. In this review, we will hence summarize the current knowledge about the close complosome-mitochondria relationship and also discuss key questions surrounding this novel research area.
- |||||||||| Journal: Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis. (Pubmed Central) - Jun 30, 2021
Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.
- |||||||||| Journal: Evidence for regulation of the complement system during pregnancy being ancient and conserved in mammals. (Pubmed Central) - Jun 24, 2021
Complement regulators CD46 and CD59 are present at the fetomaternal interface during M. domestica pregnancy as well, implying regulation of C' effector mechanisms is necessary for maintenance of normal marsupial pregnancy. Collectively these results support regulating the complement system may have contributed to the transition from oviparity to viviparity in mammals over 165 million years ago.
- |||||||||| Clinical, Journal: Trajectory of Change in Brain Complement Factors from Neonatal to Young Adult Humans. (Pubmed Central) - Jun 22, 2021
We do not find evidence of induction of complement factors during adolescence and instead find increased or sustained levels of complement inhibitor mRNA at maturation. Dysregulation of these typical patterns of complement may predispose the brain to neurodevelopmental disorders such as autism or schizophrenia.
- |||||||||| Review, Journal: Complement and human T cell metabolism: Location, location, location. (Pubmed Central) - Jun 4, 2021
Here, we summarize the current knowledge about the emerging functions of the complosome in T cell metabolism. We further place complosome activities among the non-canonical roles of other intracellular innate danger sensing systems and argue that a "location-centric" view of complement evolution could logically justify its close connection with the regulation of basic cell physiology.
- |||||||||| [VIRTUAL] Investigating the complement system in the radioresistance of rectal cancer () - May 30, 2021 - Abstract #EACR2021EACR_2531;
Conclusion We demonstrate for the first time that complement is active in CRC cells, with increased complement expression associated with radioresistance, highlighting a potential role for complement in rectal cancer radioresistance. Increased pre-treatment C3a serum levels were associated with a subsequent poor response to neo-CRT, suggesting complement may have potential as a biomarker of response to neo-CRT in rectal cancer.
- |||||||||| [VIRTUAL] Investigating the complement system in the radioresistance of rectal cancer () - May 30, 2021 - Abstract #EACR2021EACR_2530;
Conclusion We demonstrate for the first time that complement is active in CRC cells, with increased complement expression associated with radioresistance, highlighting a potential role for complement in rectal cancer radioresistance. Increased pre-treatment C3a serum levels were associated with a subsequent poor response to neo-CRT, suggesting complement may have potential as a biomarker of response to neo-CRT in rectal cancer.
- |||||||||| [VIRTUAL] Investigating the complement system in the radioresistance of rectal cancer () - May 30, 2021 - Abstract #EACR2021EACR_2529;
Conclusion We demonstrate for the first time that complement is active in CRC cells, with increased complement expression associated with radioresistance, highlighting a potential role for complement in rectal cancer radioresistance. Increased pre-treatment C3a serum levels were associated with a subsequent poor response to neo-CRT, suggesting complement may have potential as a biomarker of response to neo-CRT in rectal cancer.
- |||||||||| [VIRTUAL] Investigating the complement system in the radioresistance of rectal cancer () - May 30, 2021 - Abstract #EACR2021EACR_2528;
Conclusion We demonstrate for the first time that complement is active in CRC cells, with increased complement expression associated with radioresistance, highlighting a potential role for complement in rectal cancer radioresistance. Increased pre-treatment C3a serum levels were associated with a subsequent poor response to neo-CRT, suggesting complement may have potential as a biomarker of response to neo-CRT in rectal cancer.
- |||||||||| [VIRTUAL] The C3-like molecule CD109 controls Th1 versus Th17 induction in CD4+ T cells () - May 19, 2021 - Abstract #IMMUNOLOGY2021IMMUNOLOGY_1377;
Instead, CD109 engages with a non-canonical costimulatory molecule and controls stemness- and metabolism-related signaling pathways. Together, these data suggest that the complement-related protein CD109 serves as an important and novel molecular switch on CD4+ T-cells, where it regulates the balance between Th1 and Th17-induction pathways.
- |||||||||| [VIRTUAL] The C3-like molecule CD109 controls Th1 versus Th17 induction in CD4+ T cells () - May 19, 2021 - Abstract #IMMUNOLOGY2021IMMUNOLOGY_364;
Instead, CD109 engages with a non-canonical costimulatory molecule and controls stemness- and metabolism-related signaling pathways. Together, these data suggest that the complement-related protein CD109 serves as an important and novel molecular switch on CD4+ T-cells, where it regulates the balance between Th1 and Th17-induction pathways.
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[VIRTUAL] HTFPI.hCD47 and Adhesion Inhibition in GTKO.hCD46 Pig Lung Xenograft Injury () - May 18, 2021 - Abstract #ATC2021ATC_1933; While additional adhesion inhibitor reduced PVR elevation associated with hTFPI.hCD47 expression, it didn’t significantly attenuate neutrophil or platelet sequestration by the lung. We conclude that non-canonical adhesive mechanisms mediate the adhesion of human formed blood elements to pig endothelium that occurs even in the context of multiple genetic modifications and drug treatments designed to attenuate lung xenograft injury by these pathways.
- |||||||||| [VIRTUAL] Cellular Landscape of Steatotic Livers Revealed by Single-nuclei Rna Sequencing () - May 18, 2021 - Abstract #ATC2021ATC_1262;
We conclude that non-canonical adhesive mechanisms mediate the adhesion of human formed blood elements to pig endothelium that occurs even in the context of multiple genetic modifications and drug treatments designed to attenuate lung xenograft injury by these pathways. These results support the use of single liver cell transcriptomics as a tool to identify specific cells/pathways that may represent targets for IRI therapeutic intervention for expanding the use of fatty liver organs
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