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Oxidative stress, orchestrated by myeloperoxidase (MPO), plays crucial roles in the progression of many diseases. Nonetheless, the role of MPO‐mediated oxidative stress in distinct factor‐induced acute liver injuries (ALI) is still up for dispute, mainly due to the lack of probes for in vivo monitoring of MPO releases. Here, a highly selective MPO probe (CSQ) based on the epoxidation biochemical reaction within the MPO‐H2O2‐Cl− system is screened to construct dual near infrared‐IIb (NIR‐IIb) ratiometric (F1550Em, 808Ex/F1550Em, 980Ex) luminescence nanoprobes by integrating CSQ onto down conversion nanoparticles (DCNPs) with and without liver‐targeting moiety (twin NIR‐IIb nanoprobes). Liver‐targeting probes are employed to monitor MPO release, whereas non‐liver‐targeting probes are utilized to assess MPO activity across all cell types. Using twin NIR‐IIb nanoprobes, the MPO‐mediated oxidative stress progressively increased are observed in carbon tetrachloride (CCl4)‐induced ALI over 12 h. In contrast, the MPO‐mediated oxidative stress in acetaminophen (APAP)‐induced ALI initially increased, peaked within 3 h, and then rapidly weakened to normal levels within 12 h. Importantly, the differential release of MPO from neutrophils/Kupfer cells to extracellular fluids in the two types of ALI is revealed. This work reveals significant differences in MPO distribution and the role of MPO‐mediated oxidative stress in CCl4 and APAP‐induced ALI. [ABSTRACT FROM AUTHOR]

Liver disorders represent a significant global health burden, necessitating the exploration of innovative therapeutic interventions. Vaccaria pyramidata, a perennial plant with rhizomatous roots, has a rich history in traditional medicine, exhibiting diverse pharmacological activities. This study delved into the hepatoprotective potential of an ethanolic extract derived from Vaccaria pyramidata roots using a CCl4-induced liver injury model in Wistar albino rats. Pretreatment with the ethanolic extract of Vaccaria pyramidata roots demonstrated remarkable hepatoprotective effects, significantly attenuating CCl4-induced hepatotoxicity. Notably, the extract exhibited superior efficacy in reducing elevated serum enzyme levels, including serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and alkaline phosphatase, compared to untreated toxic rats. Furthermore, administration of the extract led to a substantial decrease in direct bilirubin levels, highlighting its potential in ameliorating liver dysfunction. Intriguingly, the ethanolic extract of Vaccaria pyramidata roots exhibited potent antioxidant activity, as evidenced by its ability to scavenge free radicals in DPPH and ABTS assays, along with a high total flavonoid content. Additionally, the extract demonstrated efficacy in reducing triglyceride levels, suggesting potential lipidlowering effects. These findings underscore the promising therapeutic potential of Vaccaria pyramidata root ethanolic extract as a novel hepatoprotective agent. Further research is warranted to elucidate its underlying mechanisms of action and explore its clinical applications in the management of liver disorders. [ABSTRACT FROM AUTHOR]

Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury. Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 µmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3-MSC-Exo, and 4-H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection. Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-a), total oxidant levels, liver aminotransferases, and cellular apoptosis. Conclusions: MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes. [ABSTRACT FROM AUTHOR]

Introduction: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury. Methods and Materials: Human umbilical cord-derived MSC (huc-MSC) cultured in a 75cm3 flask and when confluency reached about 80%, the culture medium replaced with a serum-free medium, and 48 h later supernatants collected, concentrated, and then MSC-Exo extracted. To obtain H2S-Exo, MSC was treated with NaHS (1μmol), the supernatant collected after 48 hours, concentrated and exosomes extracted. Twenty-four male mice were randomly divided into four groups (n=6) including: 1-control, 2-PBS+CCl4, 3-MSC-Exo+CCl4, and 4-H2S-Exo+CCl4. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection. Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis. MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Conclusion: Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes. [ABSTRACT FROM AUTHOR]

Liver injury is an important cause of serious liver disease. This study aims to explore the effects of miR‐217 targeting NAT2 on hepatocyte proliferation, apoptosis, and autophagy following carbon tetrachloride (CCL4)‐induced liver injury. Rat models of CCL4‐induced liver injury were established. Healthy Wistar rats were randomized into the normal, blank, negative control (NC), microRNA‐217 (miR‐217) mimic, miR‐217 inhibitor, small interfering RNA (siRNA)‐N‐acetyltransferase 2 (NAT2), and miR‐217 inhibitor + siRNA‐NAT2 groups. NAT2 activity was evaluated with reversed‐phase high‐performance liquid chromatographic method. Immunohistochemistry was used to detect NAT2 protein positive rate. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine expressions of miR‐217, NAT2, Bcl‐2, Bax, p35, LC3‐II, Becline‐1, and the ratio of caspase‐3/cleaved caspase‐3. Autophagy, proliferation, and cell cycle distribution were determined by electron microscope, CCK‐8, and flow cytometry. NAT2 protein positive rate and miR‐217, NAT2, Bcl‐2, and p35 expressions were higher and Bax, LC3‐II, and Becline‐1 expressions and the ratio of caspase‐3/cleaved caspase‐3 lower in the normal group than the other six groups. Compared with the blank and NC groups, in the miR‐217 mimic and siRNA‐NAT2 groups, Bax, LC3‐II, and Becline‐1 expressions and the ratio of caspase‐3/cleaved caspase‐3, and hepatocyte apoptosis and autophagy increased, while NAT2, Bcl‐2, and p35 expressions and hepatocyte proliferation decreased; opposite results were observed in the miR‐217 inhibitor group. Collectively, miR‐217 targeting NAT2 inhibits proliferation and promotes apoptosis and autophagy of hepatocytes in CCL4‐induced liver injury. miR‐217 targeting NAT2 inhibits proliferation and promotes apoptosis and autophagy of hepatocytes in CCL4‐induced liver injury. [ABSTRACT FROM AUTHOR]