Tuberculosis, Journal Year: 2024, Volume and Issue: 148, P. 102542 - 102542
Published: July 11, 2024
Language: Английский
Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(6), P. 570 - 582
Published: April 25, 2023
Abstract Mesenchymal stromal cells (MSCs) have been extensively tested for the treatment of numerous clinical conditions and demonstrated good safety but mixed efficacy. Although this outcome can be attributed in part to heterogeneity cell preparations, lack mechanistic understanding tools establish pharmacokinetics pharmacodynamics, as well poorly defined criteria patient stratification, hampered design informative trials. We others that MSCs rapidly undergo apoptosis after their infusion. Apoptotic are phagocytosed by monocytes/macrophages then reprogrammed become anti-inflammatory cells. MSC occurs when injected into patients who harbor activated cytotoxic T or NK Therefore, activation state used a biomarker predict responses treatment. Building on large body preexisting data, an alternative view mechanism is inflammation-dependent secretome largely responsible immunomodulatory activity. will discuss how these different mechanisms coexist instructed two types “licensing”: one cell-contact dependent second mediated inflammatory cytokines. The varied complex which orchestrate function specifically driven inflammation support physiological role tissue stroma homeostasis, it acts sensor damage initiator repair reprogramming environment.
Language: Английский
Citations
56
Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101805 - 101805
Published: July 8, 2023
Language: Английский
Citations
31
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: Feb. 22, 2025
A craniotomy is a neurosurgical procedure performed to access the intracranial space. In 3–5% of cases, infections can develop, most caused by Staphylococcus aureus biofilm formation on skull surface. Medical management this infection difficult, as properties confer immune and antimicrobial recalcitrance necessitate additional surgical procedures. Furthermore, treatment failure rates be appreciably high. These factors, compounded with rapidly expanding resistance, highlight need develop alternative strategies target reverse dysfunction that occurs during infection. Our recent work has identified CD4+ Th1 Th17 cells potent regulators innate cell activation Here, we report role IFN-γ, versus other Th1- Th17-derived cytokines, in programing response using both global type-specific IFN-γR1-deficient (Ifngr1−/−) mice. Bacterial burdens were significantly higher Ifngr1−/− relative WT animals despite few changes abundance. Single-cell transcriptomics candidate explanations for phenotype alterations death pathways, activation, MHC-II expression, T responses reduced While caspase-1 PMNs macrophage/microglial expression regulated IFN-γ signaling, no phenotypes observed either granulocyte- or macrophage/microglia conditional knockout mice, suggestive redundancy. Instead, decreased Th1/Th17 ratio was corroborated elevated IL-17 levels correlated dysfunctional cell-innate communication. Further, less effective than promoting S. bactericidal activity microglia macrophages. Collectively, identifies key protective enhancing macrophage microglial antibacterial activity. Therefore, controlled programming may represent novel therapeutic strategy chronic infections.
Language: Английский
Citations
1
Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 197, P. 104340 - 104340
Published: April 1, 2024
Pyroptosis can be triggered through both canonical and non-canonical inflammasome pathways, involving the cleavage of gasdermin (GSDM) protein family members, like GSDMD GSDME. The impact pyroptosis on tumors is nuanced, because its role in regulating cancer progression anti-tumor immunity may vary depending tumor type, stage, location, immune status. However, cannot simply categorized as promoting or inhibiting based solely whether it acute chronic nature. interplay between intricate, with some evidence suggesting that facilitate growth, while induction could stimulate anti-cancer responses. Tumor hypoxia activates inducible factor (HIF) signaling to modulate checkpoint expression. Targeting this hypoxia-pyroptosis-immune escape axis a promising therapeutic strategy. This review highlights complex crosstalk hypoxia, pyroptosis, evasion TME.
Language: Английский
Citations
6
Science Advances, Journal Year: 2023, Volume and Issue: 9(36)
Published: Sept. 6, 2023
Trained immunity is a long-term memory of innate immune cells, generating an improved response upon reinfection. Shigella important human pathogen and inflammatory paradigm for which there no effective vaccine. Using zebrafish larvae, we demonstrate that after training, neutrophils are more efficient at bacterial clearance. We observe Shigella-induced protection nonspecific has differences with training by BCG β-glucan. Analysis histone ChIP-seq on trained revealed deposits the active H3K4me3 mark promoter regions 1612 genes, dramatically changing epigenetic landscape toward enhanced microbial recognition mitochondrial ROS production. Last, plays key role in antimicrobial activity neutrophils. It envisioned signals mechanisms discover here can be used other vertebrates, including humans, to suggest new therapeutic strategies involving control infection.
Language: Английский
Citations
16
Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 4, 2024
Programmed cell death (PCD) is the collective term for intrinsically regulated of cells. Various types are triggered by their own programmed regulation during growth and development organisms, as well in response to environmental disease stresses. PCD encompasses apoptosis, pyroptosis, necroptosis, autophagy, other forms. plays a crucial role not only organisms but also serving component host innate immune defense bacterial virulence strategy employed pathogens invasion. The zoonotic pathogen Salmonella has ability modulate multiple forms PCD, including within organism. This modulation subsequently impacts infection process. review aims consolidate recent findings regarding mechanisms which initiates controls signaling, ways various can impede or restrict proliferation, interplay between pathways that counteract -induced suppression death. Ultimately, these insights may contribute novel perspectives diagnosis treatment clinical -related diseases.
Language: Английский
Citations
4
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Oct. 23, 2024
The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans animals. infection can cause intestinal damage, resulting inflammation disruption of homeostasis more severe cases lead to bacteremia. Pyroptosis, a proinflammatory form programmed cell death, involved many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental preservation homeostasis. In recent years, in-depth study our comprehension virulence factors effector proteins has reached an extensive level, deficit persists knowledge regarding intrinsic pathogenic mechanisms about necessitating continued pursuit understanding investigation. this review, we discuss occurrence pyroptosis induced by effectors provide new ideas elucidating regulatory through which trigger could pave way novel concepts strategies clinical prevention treatment associated diseases.
Language: Английский
Citations
4
Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156517 - 156517
Published: Feb. 14, 2025
Berberine (BBR), an isoquinoline alkaloid, has been applied clinically to treat dysentery caused by Shigella for decades. Nevertheless, the precise mechanisms behind its anti-Shigella effect have not fully elucidated. This study aims investigate mechanism of BBR on antibacterial activity against S. flexneri infection. We initially reproduced mouse model flexneri-induced dysentery, and then, assessed therapeutic BBR. In vitro, we measured inhibitory GTPase FtsZ (filamentous temperature sensitive protein Z) using minimum concentration (MIC) test enzyme assay bacteria-directed mechanisms. Subsequently, utilized both in vivo vitro macrophage infection with explore host-directed The canonical pyroptosis pathway mediated caspase-1 mitochondrial damage were examined Western blot, immunofluorescence RNA interference analysis. Administration alleviated symptoms induced could inhibit growth targeting FtsZ, thereby affecting bacterial cell division. Additionally, our findings revealed that suppressed inhibiting expression subsequently damage, which turn reduced intestinal inflammation tissue damage. Our results provide a novel BBR's action, targets bacterium host exert effects. Furthermore, it also provides explanation discrepancy between relatively modest efficacy enhanced effects vivo, thus, giving support clinical use.
Language: Английский
Citations
0
Small, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 28, 2025
Abstract Cancer remains one of the leading causes death individuals globally. Conventional treatment techniques like chemotherapy and radiation often suffer various drawbacks toxicity drug resistance. The study cell has been predominantly focused on classical forms apoptosis, but role metal ions in governing controlled is a fascinating less explored area. Metal‐mediated process where triggers via unique mechanism. Nanomaterial‐based strategies have gained attention for their ability to deliver precise therapeutic agents while also triggering Regulated Cell Death (RCD) mechanisms cancer cells. recently discovered metal‐mediated cuproptosis ferroptosis can be used as they selectively drug‐resistant cancer. Nano material‐based delivery system targeted sites. In this review, we given some idea about mechanism (ferroptosis cuproptosis) how initiate deaths using nanomaterials treatment.
Language: Английский
Citations
0
Medicinska istrazivanja, Journal Year: 2025, Volume and Issue: 58(1), P. 61 - 73
Published: Jan. 1, 2025
Cell death emerges during embryonic development, and is preserved after the birth as an important process for maintaining homeostasis by removing damaged or aged cells. Two forms of cell deaths exist: accidental regulated death. Necrosis accidental, unregulated, passive form that occurs due to collapse cellular homeostatic mechanisms under extreme non-physiological conditions. Regulated active, energy-dependent functions a physiological mechanism in numerous pathological conditions when it provides selective elimination potentially dangerous infected There are many types death: intrinsic extrinsic apoptosis, autophagy dependent death, necroptosis, pyroptosis, ferroptosis, parthanatos, mitochondrial permeability transition-driven necrosis, lysosome-dependent immunogenic entosis NET-osis. Different interconnected. Abnormal activation different can cause diseases. Dysregulation apoptotic program lead hyperplasia, autoimmune diseases tumorigenesis, pyroptosis associated with bacterial infection necroptosis human inflammatory skin carcinogenesis. Understanding regulatory apoptosis led discovery BH3 mimetics, drugs used treatment some B malignancies. Drugs target investigation could be future therapies various diseases, including cancer. The aim this review summarize new knowledge about processes emphasize importance newly discovered molecular pathways regulating enhancing our comprehension health disease.
Language: Английский
Citations
0