Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein.

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.

In vitro antimetastatic potential of pseudolaric acid B in HSC-3 human tongue squamous carcinoma cell line.

OBJECTIVE: Pseudolaric acid B (PAB) is a novel diterpenoid derived from the traditional Chinese medicinal herb Cortex pseudolaricis that exerts anticancer, anti-inflammatory, and immunomodulatory properties. While the anticancer potential of PAB has been studied, its effects on metastasis have not been well-studied. This study aims to determine the inhibitory effects of PAB on HSC-3 human tongue squamous cell carcinoma (TSCC) cell line. DESIGN: Cell viability and soft agar colony formation assays were conducted to assess cellular proliferation and in vitro tumorigenic capacity of TSCC cells, respectively. Additionally, wound healing, transwell migration, and invasion assays were conducted to monitor the aggressive behavior of TSCC cells. Furthermore, Western blotting analysis was conducted to reveal the signaling pathways involved in the modulation of epithelial-mesenchymal transition (EMT). RESULTS: The migratory and invasive capacities of HSC-3 cells were suppressed by PAB irrespective of their proliferation states. PAB's effects on EMT involved upregulation of E-cadherin expression and downregulation of Twist; these were concomitantly accompanied by downregulated phosphorylation of epidermal growth factor receptor (EGFR). CONCLUSIONS: PAB suppresses human TSCC in vitro by regulating Twist/E-cadherin through the EGFR signaling pathway. PAB may have potential as a candidate antimetastatic drug for TSCC treatment.

Are there effects of light exposure on daytime sleep for rotating shift nurses after night shift?: an EEG power analysis.

Introduction: Night-shift workers often face various health issues stemming from circadian rhythm shift and the consequent poor sleep quality. We aimed to study nurses working night shifts, evaluate the electroencephalogram (EEG) pattern of daytime sleep, and explore possible pattern changes due to ambient light exposure (30 lux) compared to dim conditions (<5 lux) during daytime sleep. Moethods: The study involved 31 participants who worked night shifts and 24 healthy adults who had never worked night shifts. The sleep macro and microstructures were analyzed, and electrophysiological activity was compared (1) between nighttime sleep and daytime sleep with dim light and (2) between daytime sleep with dim and 30 lux light conditions. Results: The daytime sleep group showed lower slow or delta wave power during non-rapid eye movement (NREM) sleep than the nighttime sleep group. During daytime sleep, lower sigma wave power in N2 sleep was observed under light exposure compared to no light exposure. Moreover, during daytime sleep, lower slow wave power in N3 sleep in the last cycle was observed under light exposure compared to no light exposure. Discussion: Our study demonstrated that night shift work and subsequent circadian misalignment strongly affect sleep quality and decrease slow and delta wave activities in NREM sleep. We also observed that light exposure during daytime sleep could additionally decrease N2 sleep spindle activity and N3 waves in the last sleep cycle.

Long-term night-shift work is associated with accelerates brain aging and worsens N3 sleep in female nurses.

BACKGROUND: Shift work disrupts circadian rhythms and alters sleep patterns, resulting in various health problems. To quantitatively assess the impact of shift work on brain health, we evaluated the brain age index (BAI) derived from sleep electroencephalography (EEG) results in night-shift workers and compared it with that in daytime workers. METHODS: We studied 45 female night shift nurses (mean age: 28.2 ± 3.3 years) and 44 female daytime workers (30.5 ± 4.7 years). Sleep EEG data were analyzed to calculate BAI. The BAI of night shift workers who were asleep during the daytime with those of daytime workers who were asleep at night were statistically compared to explore associations between BAI, duration of shift work, and sleep quality. RESULTS: Night-shift workers exhibited significantly higher BAI (2.14 ± 6.04 vs. 0 ± 5.35), suggesting accelerated brain aging and altered sleep architecture, including reduced delta and sigma wave frequency activity during non-rapid eye movement sleep than daytime workers. Furthermore, poor deep sleep quality, indicated by a higher percentage of N1, lower percentage of N3, and higher arousal index, was associated with increased BAI among shift workers. Additionally, a longer duration of night-shift work was correlated with increased BAI, particularly in older shift workers. CONCLUSION: Night-shift work, especially over extended periods, may be associated with accelerated brain aging, as indicated by higher BAI and alterations in sleep architecture. Interventions are necessary to mitigate the health impacts of shift work. Further research on the long-term effects and potential strategies for sleep improvement and mitigating brain aging in shift workers is warranted.

Caffeic acid phenethyl ester: Unveiling its potential as a potent apoptosis inducer for combating hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare form of head and neck cancer that is notorious for its poor prognosis and low overall survival rate. This highlights the need for new therapeutic options for this malignancy. The objective of the present study was to examine the ability of caffeic acid phenethyl ester (CAPE), which is an active compound found in propolis, to combat HSCC tumor growth. CAPE exerted its tumor­suppressive activity in HSCC cell lines through the induction of apoptosis. Mechanistically, the CAPE­mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase­9. CAPE also modulated survivin and X­linked inhibitor of apoptosis, which are potent members of the inhibitors of apoptosis protein family, either through transcriptional or post­translational regulation, leading to HSCC cell line death. Therefore, the findings of the present study suggested that CAPE is an effective treatment alternative for HSCC via the stimulation of mitochondria­dependent apoptosis.

Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis.

PURPOSE: This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer. METHODS: We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib's anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4'-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model. RESULTS: Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights. CONCLUSION: Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.