Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT. HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting. The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100-5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations. This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent.

Oxidative stress plays a critical role in the pathogenesis of hearing loss, and 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) exerts antioxidant effects by inhibiting reactive oxygen species (ROS) generation. With the aim of developing new therapeutic strategies for oxidative stress, this study investigated the protective mechanism of THSG in vitro using a normal mouse cochlear cell line (UB/OC-2). The THSG and ascorbic acid have similar free radical scavenger capacities. H₂O₂, but not THSG, reduced the UB/OC-2 cell viability. Moreover, H₂O₂ might induce apoptosis and autophagy by inducing morphological changes, as visualized by microscopy. As evidenced by Western blot analysis and monodansylcadaverine (MDC) staining, THSG might decrease H₂O₂-induced autophagy. According to a Western blotting analysis and Annexin V/PI and JC-1 staining, THSG might protect cells from H₂O₂-induced apoptosis and stabilize the mitochondrial membrane potential. Furthermore, THSG enhanced the translocation of nucleus factor erythroid 2-related factor 2 (Nrf2) into the nucleus and increased the mRNA and protein expression of antioxidant/detoxifying enzymes under H₂O₂-induced oxidative stress conditions. Collectively, our findings demonstrate that THSG, as a scavenging agent, can directly attenuate free radicals and upregulate antioxidant/detoxifying enzymes to protect against oxidative damage and show that THSG protects UB/OC-2 cells from H₂O₂-induced autophagy and apoptosis in vitro.

Background: Hepatitis B virus carriers who receive systemic cancer chemotherapy have been found to be at a higher risk of hepatitis B virus reactivation. However, lack of standard prophylaxis protocol resulted in life-threatening adverse events. Objective: This retrospective study is to investigate prevalence and chemotherapy drug-induced hepatitis B virus reactivation in all types of cancer patients and establish an institutional clinical practice protocol. Methodology: This retrospective cohort study evaluated the incidence of hepatitis B virus infection, the pre-chemotherapy screening rate of hepatitis B surface antigen (HBsAg), and the severity of hepatitis B virus reactivation of cancer patients receiving intravenous chemotherapy between 2013 and 2014. Patients receiving local chemotherapy with intra-cavity instillation, drug- or alcohol-related hepatitis, or chemotherapy for immune diseases were excluded. Results: In total 784 patients, 404 patients (51.53%) underwent hepatitis B virus serum antigen (HBsAg) testing before chemotherapy, and 61 patients (7.78%) tested positive. Only 32 patients (4.08%) received prophylactic hepatitis B virus antiviral therapy. Patients receiving prophylactic antiviral drugs were significantly lower risk of hepatitis B virus reactivation than nonprophylaxis (relative risk, RR: 0.53, number needed to treat, NNT: 12). Moreover, our study found specific single or combined chemotherapy that may cause hepatitis B virus reactivation different from those of other studies conducted in Western countries. The differences may refer to enzymes, proteins and immune response of patients. Conclusions: Our findings indicate that cancer patients receiving prophylactic antiviral drugs remain at risk of hepatitis B virus reactivation during chemotherapy. Therefore, the hepatitis B virus screen and chemotherapy control system was established in 2017 to reduce the risk of hepatitis B virus reactivation and improve patient safety.

The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population‐based retrospective cohort study using the Longitudinal Health Insurance Database 2000 available in Taiwan. This large, observational study included 46,201 patients with depression and a 1 : 1 age‐ and sex‐matched nondepression cohort enrolled between January 1, 2000, and December 31, 2013, and the newly diagnosed T2DM incidence rates were determined. We estimated the effects of depression on T2DM and the cumulative incidence curves by Cox proportional regression hazard models and Kaplan‐Meier methods, respectively. We found that 47.97% of the patients with depression did not receive ADM. Among patients with depression who received ADM, 29.71%, 6.29%, 0.05%, 9.65%, and 6.32% received selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), heterocyclic antidepressants, and other medications, respectively. Patients without ADM treatment had a 39% higher risk of developing T2DM. However, those who received ADM treatment had a significantly lower risk of T2DM development in every treatment category. Depressive disorder treated with ADMs, especially with long‐term use, was associated with an 11–48% decrease in the risk of T2DM in all ADM groups; however, heterocyclic antidepressant treatment for shorter periods (<80 days) was not significantly associated with a decreased risk of T2DM. The incidence of T2DM in Taiwan was found to be associated with an a priori history of depression and was inversely correlated with ADM treatment.