Cardiovascular and Metabolic Science, Journal Year: 2024, Volume and Issue: 35(4), P. 157 - 167
Published: Jan. 1, 2024
Nature Immunology, Journal Year: 2025, Volume and Issue: 26(1), P. 29 - 41
Published: Jan. 1, 2025
Language: Английский
Citations
1
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117303 - 117303
Published: Aug. 18, 2024
The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject debate. Here, we examined the effects PPARβ/δ agonist on pathogenesis liver and activation stellate cells (HSCs), main effector fibrosis, response to pro-fibrotic stimulus transforming growth factor-β (TGF-β). GW501516 completely prevented glucose intolerance peripheral insulin resistance, blocked accumulation collagen liver, attenuated expression inflammatory fibrogenic genes mice fed choline-deficient high-fat diet (CD-HFD). antifibrogenic effect observed livers CD-HFD-fed could occur through an action HSCs since primary isolated from Ppard
Language: Английский
Citations
7
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 26, 2024
Background Metabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty (NAFLD), is a leading cause of chronic worldwide. In 20%–30% MASLD patients, the progresses to metabolic steatohepatitis (MASH, NASH) which can lead fibrosis/cirrhosis, failure as well hepatocellular carcinoma (HCC). Here we investigated role histidine-rich glycoprotein (HRG), plasma protein produced by hepatocytes, in MASLD/MASH progression and HCC development. Methods The HRG was morphological, cellular, molecular biology approaches (a) knock-out mice (HRG −/− mice) fed on CDAA dietary protocol or MASH related diethyl-nitrosamine/CDAA hepatocarcinogenesis, (b) THP1 monocytic cells treated with purified HRG, (c) well-characterized cohorts patients without HCC. Results non-neoplastic settings, murine clinical data indicate that increases significantly parallel progression. particular, higher levels were detected subjects extensive fibrosis/cirrhosis. When submitted pro-carcinogenic protocol, showed significant decrease volume number nodules relation decreased infiltration macrophages producing pro-inflammatory mediators, including IL-1β, IL-6, IL-12, IL-10, VEGF impaired angiogenesis. histopathological analysis (H-score) MASH-related positivity peritumoral tissue correlates lower overall patient survival an increased recurrence. Moreover, increase cirrhotic (F4) carrying vs. F0/F1 patients. Conclusion Murine plays supporting specific population tumor-associated response pro-angiogenetic capabilities critically support cancer cell survival. Furthermore, our suggest possible prognostic predictor MASLD/MASH-related HCCs.
Language: Английский
Citations
4
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: May 15, 2024
Non-alcoholic fatty liver disease (NAFLD) presents as a common characterized by an indistinct pathogenesis. Disulfidptosis is recently identified mode of cell death. This study aimed to investigate the potential role disulfidptosis-related genes (DRGs) in pathogenesis NAFLD.
Language: Английский
Citations
4
Phytomedicine, Journal Year: 2024, Volume and Issue: 131, P. 155776 - 155776
Published: May 24, 2024
Non-alcoholic fatty liver disease (NAFLD) is a challenging to interfere with and represents potential long-term risk factor for hepatic fibrosis cancer. The Xiezhuo Tiaozhi (XZTZ) formula, water extract from crude herbs, has been widely used as an anti-NAFLD agent through clinical observation. However, the underlying pharmacological mechanisms of XZTZ formula its impact on pathways against NAFLD have not elucidated. Our study aims investigate effects regulatory treat NAFLD. possible active components were identified using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) molecular docking. To further explore mechanisms, forty-eight 6-week-old male C57BL/6J mice given individual attention high-fat high-sugar diet (HFHSD) or relevant control (Ctrl) diets 16 weeks successfully construct mouse model. Subsequently, levels serum biochemicals, pathological changes in liver, pyroptosis assessed therapeutic formula. Further, LPS-induced RAW264.7 cells Immortalized Mouse Kupffer (ImKC) verify vitro. We 7 chemical compounds 2 targets plausible points treatment Subsequent histopathological analysis revealed marked steatosis lipid accumulation HFHSD while conditions effectively ameliorated by administration Additionally, our work demonstrated that could attenuate M1 polarization, promote M2 suppress via SIRT1 pathway tissue samples. Moreover, validation performed ImKC showing silencing weaken relative affirmed role was associated macrophage. These findings suggest alleviated mice. ameliorations are involving attenuation promotion anti-pyroptosis pathway.
Language: Английский
Citations
4
Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156439 - 156439
Published: Jan. 1, 2025
Language: Английский
Citations
0
Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107634 - 107634
Published: Jan. 1, 2025
Language: Английский
Citations
0
The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)
Published: Feb. 14, 2025
Abstract The helminth defense molecules (HDM) are a family of immune regulatory peptides exclusively expressed by trematode worms. We have previously demonstrated that in vivo FhHDM‐1, the archetypal member HDMs, regulated macrophage responses to inflammatory ligands, thereby ameliorating progression immune‐mediated tissue damage several murine models disease. Accordingly, we postulated an understanding structure–function relationship HDMs would facilitate identification minimal bioactive peptide, which represent more synthesizable, cost‐effective, potent biotherapeutic. Thus, using combination bioinformatics, structural analyses, and cellular assays discovered 40 amino acid peptide derivative termed FhHDM‐1.C2. This contains 12 motif at its N‐terminus, facilitates interaction uptake, amphipathic α‐helix within C‐terminus, is necessary for lysosomal vATPase inhibitory activity, with both regions linked short unstructured segment. FhHDM‐1.C2 exhibits enhanced regulation function, compared full‐length prevention relapsing–remitting‐experimental autoimmune encephalomyelitis (EAE) when administered prophylactically or therapeutically. protective effect not associated global suppression, places as improved class biotherapeutics treatment diseases. Comparing from zoonotic trematodes revealed similar capacity regulation. These important new advances into lead HDM encourage further prospecting screening broader discovery novel immune‐biotherapeutics.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 12, 2025
Immune cells are central mediators of the immune response and play critical roles in pathogenesis progression liver diseases. Understanding specific contributions to disease is essential for developing targeted therapeutic strategies. In this study, we employed a two-sample Mendelian randomization (MR) approach explore potential causal relationships between peripheral cell phenotypes diseases, using genetic instrumental variables from large-scale genome-wide association studies (GWAS). Applying inverse variance weighted (IVW) methods, identified that monocyte count(odds ratio (OR) 0.81; 95% confidence interval (CI) 0.74-0.90; P = 5.95 × 10- 5, PFDR 3.57 4), CD3- lymphocyte/lymphocyte (OR 0.59, CI 0.45-0.79; 3.29 4, 5.92 3) SSC-A (Side Scatter Area) on Natural Killer (NK) 0.89, 0.82-0.95; 1.37 3, 0.0396) acted as protective factors against alcoholic disease. Similarly, trait HLA DR++ monocyte/monocyte was associated with lower risk autoimmune hepatitis 0.56, 0.41-0.79; 7.42 0.0475). Conversely, an elevated blood monocytic Myeloid-Derived Suppressor Cells (MDSCs) count higher chronic 1.23, 1.11-1.37; 1.13 1.58 3). levels DR CD14- CD16+ 0.84, 0.78-0.91; 2.07 1.32 conferred cirrhosis liver. hepatic failure, CD39+ resting CD4 regulatory T 0.85, 0.79-0.92; 1.70 5.25 played role CD28+ CD45RA- CD8dim cell/CD8dim 1.14, 1.06-1.22; 2.63 0.0406) exhibited function. Our findings highlight key pathways underscore immunomodulatory targets future interventions. Further research warranted clarify mechanistic underpinnings these associations.
Language: Английский
Citations
0
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(4), P. 167102 - 167102
Published: Feb. 28, 2024
Language: Английский
Citations
3