This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans ; Apoptosis/drug effects* ; Hep G2 Cells ; Glycyrrhetinic Acid/pharmacology* ; Doxorubicin/pharmacology* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/physiopathology* ; Mitochondria/metabolism* ; Endoplasmic Reticulum/metabolism* ; Cell Survival/drug effects* ; Membrane Proteins/genetics*

This study aims to explore the specific mechanism by which puerarin inhibits ferroptosis and improves the myocardial contractile function in myocardial hypertrophy through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) signaling pathway. The hypertrophic cardiomyocyte model was established using phenylephrine, and H9c2 cells were divided into control group, model group, puerarin group, and puerarin+ML385 group. Cell viability and surface area were detected by cell counting kit-8(CCK-8) and immunofluorescence experiments. The mitochondrial membrane potential and Ca~(2+) concentration were measured. The ferroptosis-related indicators were detected by biochemical and fluorescence staining methods. The expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway was detected by Western blot. A myocardial hypertrophy model was established, and 40 rats were randomly divided into sham group, model group, puerarin group, and puerarin+Nrf2 inhibitor(ML385) group, with 10 rats in each group. Echocardiogram, hemodynamic parameters, and myocardial hypertrophy parameters were measured. Histopathological changes of myocardial tissues were observed by hematoxylin and eosin(HE) staining and Masson staining. Biochemical methods, enzyme-linked immunosorbent assay(ELISA), and fluorescence staining were used to detect inflammatory factors and ferroptosis-related indicators. Immunohistochemistry was used to detect the expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway. Cell experiments showed that puerarin intervention significantly enhanced the viability of hypertrophic cardiomyocytes, reduced their surface area, and restored mitochondrial membrane potential and Ca~(2+) homeostasis. Mechanism studies revealed that puerarin promoted Nrf2 nuclear translocation, upregulated the expression of HO-1, solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4), and decreased malondialdehyde(MDA), reactive oxygen species(ROS), and iron levels. These protective effects were reversed by ML385. In animal experiments, puerarin improved cardiac function in rats with myocardial hypertrophy, alleviated myocardial hypertrophy and fibrosis, inhibited inflammatory responses and ferroptosis, and promoted nuclear Nrf2 translocation and HO-1 expression. However, combined intervention with ML385 led to deterioration of hemodynamics and a rebound in ferroptosis marker levels. In conclusion, puerarin may inhibit cardiomyocyte ferroptosis through the Nrf2/ARE/HO-1 signaling pathway, thereby improving myocardial contractile function in myocardial hypertrophy.
Animals ; NF-E2-Related Factor 2/genetics* ; Rats ; Ferroptosis/drug effects* ; Signal Transduction/drug effects* ; Isoflavones/pharmacology* ; Male ; Rats, Sprague-Dawley ; Cardiomegaly/genetics* ; Myocytes, Cardiac/metabolism* ; Antioxidant Response Elements/drug effects* ; Myocardial Contraction/drug effects* ; Heme Oxygenase-1/genetics* ; Cell Line

Objective To investigate the influence of the liver failing to convey and disperse on space navigation aging.Methods High and low neuroticism subjects screened by Eysenck personality questionnaire were included in liver failing to convey and disperse group and liver controlling conveyance and dispersion group,respectively.The two groups were then divided into youth and elderly groups based on age.Finally,spatial navigation task was conducted to record and analyze behavioral(reaction time and accuracy)and EEG data(amplitude and latency of P2 and N2 components)of all the four groups(30 subjects each group).Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.001)and reaction time was prolonged significantly(P<0.05).The interaction effect between age and liver regulation status showed a marginal significant difference(P=0.078).The accuracy of elderly people was lower than that of youth people(P=0.002)for liver failing to convey and disperse subjects,while there was no significant difference between the two groups for subjects with liver controlling conveyance and dispersion.The P2 amplitude in the elderly group was significantly smaller than that in the youth group(P=0.027).The amplitude of P2 in group of liver failing to convey and disperse was significantly smaller than that in group of liver controlling conveyance and dispersion(P=0.042).The interaction effect of P2 amplitude between age and liver regulation status showed a marginal significance(P=0.073).For youth subjects,the P2 amplitude in group of liver controlling conveyance and dispersion was significantly larger than that in group of liver failing to convey and disperse(P=0.007),while there was no significant difference in P2 amplitude between the two groups for the elderly subjects.The N2 amplitude for tasks of allocentric frames of reference was significantly greater than that of egocentric frames of reference(P=0.024).Conclusion Liver failing to convey and disperse caused by long-term emotional disturbance accelerates spatial navigation aging,and selective attention feature inhibition disorder may be the underlying ERPs neuroelectrophysiological mechanism.

Objective To investigate the influence of the and mechanism of liver failing to convey and disperse on age-related changes in attentional search based on ERPs.Methods oddball attention search task was administrated to record and analyze behavioral and EEG data(N2pc、SPCN、N2pc-Ptc components)of 120 subjects.Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.05).The elderly group had a lower accuracy(P<0.001)and a longer reaction time(P<0.001)compared to the young group.The N2pc amplitude in subjects with liver failing to convey and disperse was significantly greater than that in subjects with liver controlling conveyance and dispersion(P<0.05).The interaction effect of SPCN amplitude between age and liver failing to convey and disperse status was significant(P=0.024).And in the elderly group,SPCN amplitude in subjects with liver dysregulation was significantly smaller than that of liver controlling conveyance and dispersion(P=0.042).The N2pc-Ptc peak to peak amplitude interaction effect between age and liver regulation status was marginal significant(P=0.087),and in liver failing to convey and disperse group,N2pc-Ptc peak to peak amplitude of the elderly was significantly smaller than that of the young(P=0.008).Conclusion Attention search ability is impaired in the elderly with liver failing to convey and disperse,and the electrophysiological abnormalities,such as directed attention allocation,spatiotemporal dynamic cohesion and short-term memory maintenance,may be part of the mechanism.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Aplastic anemia is a rare and life-threatening bone marrow failure that is becoming more common and tends to affect younger individuals.Traditional Chinese medicine has a long history of preventing and treating asthenia and blood syndrome.Its treatment of aplastic anemia involves coordinated regulation through multiple components,targets,and channels.The article classifies and elaborates on the therapeutic effects of traditional Chinese medicine compounds and their components on aplastic anemia.As well as the expression of related factors from three aspects:hematopoietic stem/progenitor cells,the immune system,and bone marrow microenvironmental abnormalities.It also analyzes the frequency and meridian of commonly used drugs in traditional Chinese medicine compounds.Deficiency tonifying drugs were found to be the most frequently used treatment for aplastic anemia,which is consistent with the deficiency-based nature of the disease.The related organs affected are the liver,spleen,and kidney.This paper reviews the mechanism of aplastic anemia and the preventive and therapeutic effects of traditional Chinese medicine.The study is of great significance for the follow-up research on traditional Chinese medicine in improving aplastic anemia.

This study analyzed the demographic characteristics and clinically significant inflammatory index changes in listeriosis cases in China from 2010 to 2023.The aim was to understand Listeria monocytogenes susceptibility,to provide a reference for listeriosis prevention and control.Records in three Chinese databases—the China Knowledge Network,Wanfang Database,and VIP Database—from January 1,2010,to December 31,2023,were searched.Statistical analysis was conducted on the clinical features and epidemiological information for all identified cases.A total of 693 cases of listeriosis were included:482 occurring during the perinatal period and 211 occurring outside the perinatal period.The average mortality rate was 17.2%(119/693).The predominant clinical manifestations of listeriosis in neonatal patients during the perinatal period were sepsis(75.5%,241/319)and meningitis(41.1%,131/319).The mortality rate among neonatal patients was 27.1%(76/280).In patients in the non-perinatal period,meningitis(70.1%,148/211)and sepsis(43.6%,92/211)were the main clinical manifestations,and the average patient age was 47.2 years.Among patients of known age,the highest prevalence was observed in the 40-64 year age group,which accounted for 44.9%(44/98).Sixty-one cases had no other underlying diseases before infection.Reported cases of listeriosis occurred in 27 provinces(municipalities,and autonomous region)in China,and Beijing reported the most cases,accounting for 23.7%(164/693).L.monocytogenes was sensitive to β-lactam drug treatment but showed differing degrees of drug resistance.Among 145 cases,12 were resistant to penicillin,and 16 were resistant to oxacillin.Listeriosis is a foodborne disease with a high mortality rate,particularly among neonates.With the continuing emergence of drug-resistant strains,standardizing and strengthening prevention and treatment measures for this disease as early as possible are essential.

Objective To investigate the influence of the liver failing to convey and disperse on space navigation aging.Methods High and low neuroticism subjects screened by Eysenck personality questionnaire were included in liver failing to convey and disperse group and liver controlling conveyance and dispersion group,respectively.The two groups were then divided into youth and elderly groups based on age.Finally,spatial navigation task was conducted to record and analyze behavioral(reaction time and accuracy)and EEG data(amplitude and latency of P2 and N2 components)of all the four groups(30 subjects each group).Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.001)and reaction time was prolonged significantly(P<0.05).The interaction effect between age and liver regulation status showed a marginal significant difference(P=0.078).The accuracy of elderly people was lower than that of youth people(P=0.002)for liver failing to convey and disperse subjects,while there was no significant difference between the two groups for subjects with liver controlling conveyance and dispersion.The P2 amplitude in the elderly group was significantly smaller than that in the youth group(P=0.027).The amplitude of P2 in group of liver failing to convey and disperse was significantly smaller than that in group of liver controlling conveyance and dispersion(P=0.042).The interaction effect of P2 amplitude between age and liver regulation status showed a marginal significance(P=0.073).For youth subjects,the P2 amplitude in group of liver controlling conveyance and dispersion was significantly larger than that in group of liver failing to convey and disperse(P=0.007),while there was no significant difference in P2 amplitude between the two groups for the elderly subjects.The N2 amplitude for tasks of allocentric frames of reference was significantly greater than that of egocentric frames of reference(P=0.024).Conclusion Liver failing to convey and disperse caused by long-term emotional disturbance accelerates spatial navigation aging,and selective attention feature inhibition disorder may be the underlying ERPs neuroelectrophysiological mechanism.

Objective To investigate the influence of the and mechanism of liver failing to convey and disperse on age-related changes in attentional search based on ERPs.Methods oddball attention search task was administrated to record and analyze behavioral and EEG data(N2pc、SPCN、N2pc-Ptc components)of 120 subjects.Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.05).The elderly group had a lower accuracy(P<0.001)and a longer reaction time(P<0.001)compared to the young group.The N2pc amplitude in subjects with liver failing to convey and disperse was significantly greater than that in subjects with liver controlling conveyance and dispersion(P<0.05).The interaction effect of SPCN amplitude between age and liver failing to convey and disperse status was significant(P=0.024).And in the elderly group,SPCN amplitude in subjects with liver dysregulation was significantly smaller than that of liver controlling conveyance and dispersion(P=0.042).The N2pc-Ptc peak to peak amplitude interaction effect between age and liver regulation status was marginal significant(P=0.087),and in liver failing to convey and disperse group,N2pc-Ptc peak to peak amplitude of the elderly was significantly smaller than that of the young(P=0.008).Conclusion Attention search ability is impaired in the elderly with liver failing to convey and disperse,and the electrophysiological abnormalities,such as directed attention allocation,spatiotemporal dynamic cohesion and short-term memory maintenance,may be part of the mechanism.