Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.

Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

rmhTNF-α combined with cisplatin inhibits proliferation of A549 cell line in vitro.

OBJECTIVE: To explore the inhibitory effect of recombinant mutant human tumor necrosis factor-Α (rmhTNF-Α) in combination with cisplatin on human lung adenocarcinoma cell line A549. METHODS: Human lung adenocarcinoma cell line A549 was treated with varying concentrations of rmhTNF-Α (0.38, 0.75, 1.50, 6.00 and 12.00 IU/ml) or cisplatin (3.91, 7.81, 15.63, 31.25 and 62.50 Μg/ml) for 24 hours. Viable cell number was analyzed by using crystal violet staining. The inhibitory rates of A549 cells growth by the two drugs were calculated. For analyzing whether there was a synergistic effect of rmhTNF-Α with cisplatin, A549 cells were treated with 0.75 IU/ml rmhTNF-Α and increased concentrations of cisplatin. RESULTS: rmhTNF-Α or cisplatin inhibited the growth of A549 cell lines in a dose-dependent manner. The inhibitory effect of rmhTNF-Α combined with cisplatin was significantly greater than cisplatin alone at the same concentration (all P<0.01). CONCLUSION: rmhTNF-Α combined with cisplatin might have synergistic inhibitory effect on human lung adenocarcinoma cell line A549.

[Effects of human disturbance on coarse woody debris of Larix gmelinii forest on northern slope of Greater Hinggan Mountains].

An investigation was conducted on the living tree volume, coarse woody debris (CWD) loading, and composition of Larix gmelinii forest along a human disturbance gradient, i.e., no disturbance (natural larch forest), one-time disturbance (natural forest was disturbed once only), and two-time disturbance (natural forest was disturbed two times consecutively), on the northern slope of Greater Hinggan Mountains. The results showed that under no disturbance, one-time disturbance, and two-time disturbance, the average living tree volume of L. gmelinii forest was 161.6, 138.3, and 114. 8 m3 x hm(-2), and the average CWD loading was 69.77, 36.64 and 32.61 m3 x hm(-2), respectively. In natural L. gmelinii forest, most of CWD was of 20-40 cm diameter class, among which, fallen logs occupied 72%, and snags and stumps occupied 28% ; while in one-time and two-time disturbance L. gmelinii forests, most CWD was of 10-30 cm diameter class, with the fallen logs, snags, and stumps occupied 70%, 14% and 16%, and 57%, 15% and 28%, respectively. Human disturbance reduced the CWD loading of L. gmelinii forest and altered the composition of the CWD.

[Splash erosion of black soil with different reclamation years and its relations to soil aggregates selective characteristics].

Taking the typical black soil with a reclamation history of 8, 30, and 50 years and the un-reclaimed secondary forest land as test objects, a simulation study was made on the process of splash erosion and the selective characteristics of soil aggregates under artificial rainfall condition, with the effects of reclamation on the splash erosion in black soil region analyzed. The splash amount of reclaimed black soil was evidently higher than that of un-reclaimed secondary forest land, and increased with increasing reclamation years, with a variation range of 0.95-7.06 g x cm(-1). There was a significant exponential correlation between splash amount and splash distance, and the percentages of small size water-stable aggregates increased with increasing splash distance. The critical particle size of soil aggregates for the enrichment and depletion of splash erosion was 1.0 mm. Soil water-stable aggregates larger than 2 mm and smaller than 0.25 mm in size and soil organic matter content were the main factors affecting the splash erosion characteristics of typical black soil.

[Observation on therapeutic effect of jianpi huoxue herbs combined with chemotherapy in treating post-operational colonic cancer patients].

OBJECTIVE: To observe and compare the therapeutic effect of Jianpi Huoxue herbs (JPHXH) combined with chemotherapy (CT) in treating post-operational colonic cancer patients with Pi deficiency Syndrome (PDS). METHODS: Adopting randomized control trial method, 64 patients were divided into two groups. The treated group (n = 43) received JPHXH plus CT and the control group ( n = 21 ) received CT alone. A treatment course of 3 months was applied to both groups. Therapeutic effect, changes of PDS and incidence of adverse reaction in the two groups were observed. RESULTS: The tumor remission rate in the treated group and the control group was 39.5 % and 33.3 %, respectively. The effective rate on PDS in the treated group and the control group was 72.1% and 19.0%, respectively, showing significant difference (P < 0.01). The incidence of adverse reaction was lower in the treated group than that in the control group (P < 0.05). CONCLUSION: JPHXH is effective in treating post-operational colonic cancer patients with PDS and relieving the adverse reaction of chemotherapy to certain extent.