OBJECTIVE: To investigate the effect of chrysophanol, a phytochemical derived from Radix et Rhizoma Rhei on HepG2 liver cancer cells. METHODS: HepG2 cell line was treated with different concentrations chrysophanol (0-100 μmol/L) for 24 h. The cell counting kit 8 assay was employed to assess cell viability. Intracellular calcium levels were examined using Fluo-4 AM and Mag-fluo-4 AM staining, followed by flow cytometry analysis. Mitochondrial membrane potential was measured with JC-1 assay kit. Additionally, the expressions of key proteins such as p-JNK, Bax, cytochrome c (Cyt C), cleaved caspase-3 (cCaspase-3), and caspase-8 were analyzed by Western blot. The inhibitory effects of chrysophanol on the invasion of cells were determined using a Transwell assay. Analysis of invasiveness was conducted by wound healing assay. RESULTS: Chrysophanol significantly reduced the proliferation of HepG2 liver cancer cells by affecting intracellular calcium distribution, diminishing mitochondrial membrane potential, and enhancing the expressions of p-JNK, Bax, Cyt C, cCaspase-3, and caspase-8 in the groups treated with 75 or 100 μmol/L chrysophanol compared to the control group (P<0.05). Additionally, 75 and 100 μmol/L chrysophanol exhibited inhibitory effects on cell migration and wound healing. CONCLUSION Chrysophanol demonstrates potential against HepG2 liver cancer cells, suggesting its potential use as a therapeutic agent for liver cancer treatment.
Humans ; Calcium/metabolism* ; Hep G2 Cells ; Liver Neoplasms/metabolism* ; Neoplasm Invasiveness ; Membrane Potential, Mitochondrial/drug effects* ; Anthraquinones/pharmacology* ; Cell Proliferation/drug effects* ; Cell Death/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Cell Survival/drug effects*

Background/Aims:  Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods:  From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. RESULTS: Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. CONCLUSION: The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Acoustics ; Animals ; Motor Activity ; Prepulse Inhibition ; Rats ; Receptor, Serotonin, 5-HT1A ; Reflex, Startle ; Sensory Gating ; Serotonin ; Serotonin 5-HT1 Receptor Agonists ; Social Control, Formal