Investigating the Dynamic Interplay Between Cellular Immunity and Tumor Cells in the Fight Against Cancer: An Updated Comprehensive Review

Iranian Journal of Blood and Cancer, Journal Year: 2024, Volume and Issue: 16(2), P. 84 - 101

Published: June 1, 2024

Language: Английский

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Liver Fibrosis Amelioration by Macrophage-Biomimetic Polydopamine Nanoparticles via Synergistically Alleviating Inflammation and Scavenging ROS

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(6), P. 3040 - 3052

Published: May 20, 2024

The progression of liver fibrosis is determined by the interaction damaged hepatocytes, active hepatic stellate cells, and macrophages, contributing to development oxidative stress inflammatory environments within liver. Unfortunately, current pharmacological treatment for limited its inability regulate inflammation concurrently. In this study, we developed a cell membrane biomaterial fibrosis, which designated as PM. PM biomimetic nanomaterial constructed encapsulating polydopamine (PDA) with macrophage (MM). It hypothesized that nanoparticles (NPs) can successfully target site inflammation, simultaneously inhibit scavenge reactive oxygen species (ROS). vitro experiments demonstrated NPs exhibited strong antioxidant properties ability neutralize pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Moreover, capacity safeguard cells from their anti-inflammatory efficacy in an model were validated subsequent cellular experiments. Additionally, high biocompatibility. mouse observed aggregate efficiently fibrotic liver, displaying excellent properties. Notably, superior targeting, anti-inflammatory, ROS scavenging abilities inflamed tissues compared MM, PDA, or erythrocyte membrane-encapsulated PDA. Under synergistic effect anti-inflammation antioxidant, produced significant therapeutic effects on mice. conclusion, alleviation specially designed nanomaterial, NPs, provides valuable insights other inflammatory- stress-related diseases.

Language: Английский

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Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5238 - 5238

Published: May 11, 2024

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead development hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing risk developing hepatic steatosis inflammation could helpful in minimizing threat/probability organ recent years, increasing attention has been paid influence nutraceuticals prevention treatment diseases. Therefore, aim this review was describe precise role selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, curcumin. use these patients with MASLD/MASH, along behavioral pharmacological therapy, have a beneficial effect on combating inflammation, oxidative stress, thereby preventing damage.

Language: Английский

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Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is common chronic metabolic disorder which associated with fat accumulation in the liver. It causes a wide range of pathological effects such as insulin resistance, obesity, hypertension, diabetes, non-alcoholic steatohepatitis (NASH) and cirrhosis, cardiovascular diseases. The molecular mechanisms that cause initiation progression NAFLD remain fully unclear. Inflammation regarded significant mechanism could result cell death tissue injury. Accumulation leukocytes hepatic inflammation are important contributors NAFLD. Excessive inflammatory response can deteriorate injury Thus, inhibition improves by reducing intrahepatic content, increasing β-oxidation acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- γ (PPAR-γ), well attenuating hepatocyte apoptosis sensitivity. Therefore, understanding molecules signaling pathways suggests us valuable information about progression. This review aimed to evaluate on

Language: Английский

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Human umbilical cord mesenchymal stem cells inhibit liver fibrosis via the microRNA-148a-5p/SLIT3 axis

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 125, P. 111134 - 111134

Published: Oct. 31, 2023

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have garnered considerable attention as prospective modalities of treatment for liver fibrosis (LF). The inhibition hepatic stellate cell (HSC) activation underlies the anti-fibrotic effects hUC-MSCs. However, precise mechanism by which hUC-MSCs impede HSC remains unclarified. We aimed to elucidate intrinsic mechanisms underlying therapeutic in LF patients.Mice with cirrhosis induced carbon tetrachloride (CCl4) were used experimental models and administered via tail-vein injection. alterations inflammation evaluated through histopathological examinations. RNA sequencing (RNA-seq) bioinformatics analysis then conducted investigate Finally, an in-vitro experiment involving co-cultivation or hUC-MSC-derived exosomes (MSC-Exos) LX2 was performed validate potential hepatoprotective patients.hUC-MSC therapy significantly improved function alleviated CCl4-induced mice. High-throughput RNA-Seq identified 1142 differentially expressed genes that potentially involved mediating These play important role regulating extracellular matrix. miRNA expression data (GSE151098) indicated miR-148a-5p level downregulated samples, but restored following hUC-MSC treatment. delivered exosome pathway, upregulated suppressed activated phenotype cells. SLIT3 within pool target regulated miR-148a-5p. Furthermore, administration miR-148a-5p, played a crucial suppressing SLIT3, thereby palliating fibrosis.hUC-MSCs inhibit HSCs miR-148a-5p/SLIT3 pathway are thus capable alleviating LF.

Language: Английский

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Hepatic Stellate Cell- and Liver Microbiome-Specific Delivery System for Dihydrotanshinone I to Ameliorate Liver Fibrosis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(23), P. 23608 - 23625

Published: Nov. 23, 2023

Liver fibrosis is a major contributor to the morbidity and mortality associated with liver diseases, yet effective treatment options remain limited. Hepatic stellate cells (HSCs) are promising target for hepatic fibrogenesis due their pivotal role in disease progression. Our previous research has demonstrated potential of Dihydrotanshinone I (DHI), lipophilic component derived from natural herb Salvia miltiorrhiza Bunge, treating by inhibiting YAP/TEAD2 interaction HSCs. However, clinical application DHI faces challenges its poor aqueous solubility lack specificity Additionally, recent studies have implicated impact microbiota, distinct gut on pathogenesis diseases. In this study, we developed an HSC- microbiome-specific delivery system conjugating prebiotic-like cyclodextrin (CD) vitamin A, utilizing PEG2000 as linker (VAP2000@CD). results demonstrate that VAP2000@CD markedly enhances cellular uptake human HSC line LX-2 deposition fibrotic vivo. Subsequently, intervention DHI-VAP2000@CD shown notable reduction bile duct-like structure proliferation, collagen accumulation, expression fibrogenesis-associated genes rats subjected duct ligation. These effects may be attributed regulation interaction. Importantly, also restored microbial homeostasis liver, promoting amelioration inflammation. Overall, our findings indicate represents therapeutic approach specifically targeting HSCs restoring balance.

Language: Английский

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Plasticity, heterogeneity, and multifunctionality of hepatic stellate cells in liver pathophysiology

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(5)

Published: April 12, 2024

HSCs, the resident pericytes of liver, have consistently been at forefront liver research due to their crucial roles in various hepatic pathological processes. Prior literature often depicted HSCs a binary framework, categorizing them as either quiescent or activated. However, recent advances HSC research, particularly advent single-cell RNA-sequencing, revolutionized our understanding these cells. This sophisticated technique offers an unparalleled, high-resolution insight into populations, uncovering spectrum diversity and functional heterogeneity across physiological states ranging from development aging process. The RNA-sequencing revelations also highlighted intrinsic plasticity underscored complex myriad pathophysiological processes, including injury, repair, carcinogenesis. review aims integrate clarify discoveries, focusing on how inherent is central dynamic both maintaining homeostasis orchestrating responses injury. Future will whether findings rodent models can be translated human livers guide insights are harnessed develop targeted therapeutic interventions.

Language: Английский

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The phenolic compounds tyrosol and hydroxytyrosol counteract liver fibrogenesis via the transcriptional modulation of NADPH oxidases and oxidative stress-related miRNAs

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 157, P. 114014 - 114014

Published: Nov. 12, 2022

Liver fibrosis is the result of a chronic pathological condition caused by activation hepatic stellate cells (HSCs), which induces excessive deposition extracellular matrix. Fibrogenesis sustained an exaggerated production reactive oxidative species (ROS) NADPH oxidases (NOXs), are overactivated in inflammation. In this study, we investigated antifibrotic properties two phenolic compounds natural origin, tyrosol (Tyr) and hydroxytyrosol (HTyr), known for their antioxidant anti-inflammatory effects. We assessed Tyr HTyr activity both vitro, co-culture LX2, HepG2 THP1-derived Mϕ macrophages, set up to simulate microenvironment, vivo, mouse model liver obtained carbon tetrachloride treatment. evaluated mRNA protein expression profibrotic markers (α-SMA, COL1A1, NOX1/4) qPCR and/or immunocytochemistry or immunohistochemistry. The selected miRNAs livers were measured qPCR. reduces fibrogenesis vitro downregulating all fibrotic markers. Notably, they also modulated stress restoring physiological levels NOX1 NOX4. effect was accompanied transcriptional regulation inflammatory genes 2 involved control damage (miR-181-5p miR-29b-3p). conclusion, exert effects preclinical vivo models fibrosis, modulating stress, representing promising candidates further development.

Language: Английский

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Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 14(5), P. 100902 - 100902

Published: Nov. 29, 2023

Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), a process associated with ferroptosis. Ginsenoside Rb1 (GRb1), major active component extracted from Panax ginseng, inhibits HSC activation. However, potential role GRb1 in mediating ferroptosis remains unclear. This study examined effect on liver both vivo and vitro, using CCl4-induced mouse model primary HSCs, LX-2 cells. The findings revealed that effectively inactivated HSCs reducing alpha-smooth muscle actin Type I collagen levels. Moreover, significantly alleviated vivo. From mechanistic standpoint, pathway appeared to be central antifibrotic effects GRb1. Specifically, promoted characterized increased glutathione depletion, malondialdehyde production, iron overload, accumulation reactive oxygen species. Intriguingly, Beclin 1 (BECN1) levels decreased System Xc-key subunit SLC7A11. Further experiments showed BECN1 silencing inhibited GRb1-induced mitigated reduction SLC7A11 caused could directly interact SLC7A11, initiating In conclusion, suppression counteracted inactivation vitro. Overall, this highlights novel inducing promoting inactivation, at least partly through its modulation

Language: Английский

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Chinese herbal decoction, Yi-Qi-Jian-Pi formula exerts anti-hepatic fibrosis effects in mouse models of CCl4-induced liver fibrosis

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e26129 - e26129

Published: Feb. 22, 2024

BackgroundYi-Qi-Jian-Pi Formula (YQJPF) is a herbal medicine that used to treat patients with liver failure. However, scientific evidence supporting the treatment of hepatic fibrosis YQJPF has not been forthcoming. The present study aimed determine mechanisms underlying anti-fibrotic effects in mouse models fibrosis.MethodsMice were randomly assigned control, model, silymarin (positive treated), and low-, medium- high-dose (7.5, 15, 30 g/kg, respectively) groups. Liver function, inflammatory cytokines, oxygen stress analyzed using ELISA kits. Sections histopathologically stained hematoxylin-eosin, Masson trichrome, Sirius red. Macrophage polarization was measured by flow cytometry immunofluorescence. Potential targets against network pharmacology Chinese compound on transforming growth factor-beta (TGF-β)/Suppressor Mothers Decapentaplegic family member 3 (Smad3) signaling pathway assessed qRT-PCR immunohistochemical staining. Finally, metagenomics LC-MS/MS detect intestinal flora metabolites mice, an in-depth correlation analysis performed spearman analysis. data compared one-way ANOVA least significant differences (LSDs) or ANOVA-Dunnett's T3 method when no homogeneity detected.ResultsWe induced CCl4 establish found dose-dependently increased body weight, improved reversed fibrosis. Elevated levels pro-inflammatory factors IL-1β, IL-6, TNF-α model mice substantially decreased YQJPF, particularly at highest dose. Levels serum malondialdehyde superoxide dismutase (SOD) activity elevated reduced, respectively. concentration SOD group. M1 polarized macrophages (CD86) significantly M2 mildly without significance. numbers inhibited TGF-β/Smad3 signaling. Metagenomic non-targeted metabolomics detection results showed could regulate homeostasis, Spearman abundance Calditerrivibrio_nitroreducens negatively correlated 18β-glycyrrhetinic acid. It suggested may reduce anti-fibrosis effect licorice other herbs digesting acid.ConclusionsYQJPF can reverse inhibiting inflammation, suppressing oxidative stress, regulating immunological response initiated macrophages, homeostasis. Therefore, be included clinical regimens

Language: Английский

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