HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway.

The mortality rate of acute-on-chronic liver failure (ACLF) remains significantly elevated; hence, this study aimed to investigate the impact of heat shock protein family B (small) member 1 (HSPB1) on ACLF in vivo and in vitro and the underlying mechanism. This study used the ACLF mouse model, and liver damage extent was studied employing Masson trichrome, hematoxylin and eosin (H&E), Sirius red staining, and serum biochemical indices. Similarly, hepatocyte injury in lipopolysaccharide (LPS)-induced L02 cells was evaluated using cell counting kit-8 assay, enzymatic activity, flow cytometry, and TUNEL assay, while the underlying mechanism was investigated using western blot. Results showed that the morphology of liver tissue in ACLF mice was changed and was characterized by cirrhosis, fibrosis, collagen fiber deposition, inflammatory cell infiltration, and elevated liver injury indices. Moreover, HSPB1 was upregulated in both ACLF patients and mice, where overexpressing HSPB1 was found to inhibit ACLF-induced liver damage. Similarly, the HSPB1 expression in LPS-treated L02 cell lines was also increased, where overexpressing HSPB1 was found to promote cell viability, inhibit liver injury-related enzyme activity, and suppress apoptosis. Mechanistic investigations revealed that HSPB1 was responsible for inhibiting p-P53 and Bax protein levels, where activated P53 counteracted HSPB1's effects on cellular behaviors. In conclusion, HSPB1 attenuated ACLF-induced liver injury in vivo and inhibited LPS-induced hepatocyte damage in vitro, suggesting that HSPB1 may be a novel target for ACLF therapy.

CircCHD2/miR-200b-3p/HLF Axis Promotes Liver Cirrhosis.

Inactivation of hepatic stellate cells (HSCs) slows down liver cirrhosis (LC) advancement. The role of circular RNAs (circRNAs) in LC is largely undiscovered. Here, we clarified the effect of circCHD2 on HSCs. LX-2 cells were stimulated with TGF-ß1 to establish a cell model. The circCHD2, miR-200b-3p, and HLF were inspected using quantitative real-time PCR (qPCR). Cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, together with colony formation assays were all conducted to analyze cell proliferation. α-SMA and Col1A1 were evaluated by qPCR and Western blot. The targets of circCHD2 and miR-200b-3p were verified by luciferase reporter assay. We found the circCHD2 was upregulated in the patients with LC and transforming growth factor beta 1 (TGF-ß1)-stimulated LX-2 cells. Interfering of circCHD2 inhibited the proliferation induced by TGF-ß1, downregulated α-SMA, and Col1A1. CircCHD2 served as a miR-200b-3p sponge, which directly targeted downstream HLF. Downregulated miR-200b-3p abrogated suppression on the cellular process, α-SMA and Col1A1 levels induced by knockdown of circCHD2. Enforced HLF reversed the effect induced by miR-200b-3p overexpression. Taken together, a loss of circCHD2/miR-200b-3p/HLF axis contributed to alleviate LC progression. The findings suggested that circCHD2 may have potential to be a therapeutic target of LC.

Preparation of MED1(transcription mediator subunit) gene nanocarrier and its mechanism of action on liver cell regeneration in chronic acute liver failure.

Liver failure has attracted attention in clinical work due to its high mortality, and the development of liver transplantation is restricted by various factors. Therefore, it is very important to carry out research on the mechanism of liver cell regeneration. This article has studied in depth the preparation of MED1 gene nanocarriers, collected human plasmids and cells through experimental materials and experimental instruments, and conducted comparative research on conventional culture. This question conducts a regeneration experiment on liver cells in chronic-onset acute liver failure, divides patients into an experimental group and a control group, and understands the recovery of liver function according to the screening of their plasma samples and separation of plasma. This article selects the commonly used clinical biological markers, such as Na+, AFP, Alb, CHE (serum cholinesterase) and other indicators to reflect the regeneration ability of liver function. The incidence of surgical complications in the control group, such as ascites, infection, bleeding, HE, hepatorenal syndrome, and hyponatremia were 71.3%, 87.4%, 16.1%, 41.4%, 19.5%, and 33.3%, respectively. Significantly higher than the experimental group, the difference was statistically significant (P < 0.05); while gender, age, PLT level and whether to use hormones, artificial liver or not there was no significant difference between the two groups (P > 0.05).

Inhibition of Adipogenesis Is Involved in the Protective Effects of 1,25-Dihydroxy Vitamin D3 on the Radiation-Injured Bone Marrow Microenvironment in Mice.

To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy 60Coγ rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 µg/kg) was administered once per day from 2 d before to 8 d after irradiation. Mice in the IR group were treated with the same dose of γ rays and an equal volume of DMSO. Subsequently, the body weights and the numbers of peripheral white blood cells (WBCs) were measured. Histological analysis of femur bone marrow was conducted to determine the proportion of adipose area as well. Finally, the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in bone marrow was detected by immunohistochemistry. After irradiation, the percentage of adipose area in the bone marrow was significantly increased, and the WBC number and body weight were markedly reduced. Compared with irradiation alone, the co-administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation-induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells expressing PPARγ and enhanced the recovery of body weight and WBCs. These results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation-induced adipogenesis via the down-regulation of PPARγ expression.

[Salinomycin Enhances the Apoptosis of T-cell Acute Lymphoblastic Leukemia Cell Line Jurkat Cells Induced by Vincristine].

OBJECTIVE: This study was aimed to investigate the effect of salinomycin combined with vincristine on the proliferation and apoptosis of Jurkat cells and its possible mechanisms. METHODS: The proliferation of Jurkat cells was examined by CKK-8 assay. Flow cytometry was used to assess cellular apoptosis. Levels of BCL-2, caspase-3, and caspase- 8 were measured by Western blot. RESULTS: The salinomycin or vincristine, either alone or in combination, inhibited the proliferation of Jurkat cells in a dose-dependent manner. Salinomycin combined with vincristine produced more obveous inhibition of cell proliferation than either compound used alone (P<0.05). Western blot analysis showed that the combined use of Sal and VCR reduced the expression of BCL-2 protein, and increased expression of caspase 3 and caspase 8 protein, more significantly. Furthermore, combination of Sal and VCR synergistally promoted apoptosis of the Jurkat cells (P<0.05). CONCLUSION: The combination of salinomycin and vincristine synergistically inhibits proliferation and promotes apoptosis of T-cell acute lymphoblastic leukemia Jurkat cells.