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To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 μg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.

AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin, and MTT assay used to evaluate the inhibition rate of the two compounds on cells. Then, the cell cycle distribution and apoptosis were detected by flow cytometry, and changes in apoptosis-related proteins such as death receptor 5 (DR5), a-caspase-3, and x-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. MUM-2B cells were transfected with si-DR5, which interfered with the expression of the DR5 gene. MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins. RESULTS: When TRAIL and oridonin were simultaneously administered to the MUM-2B cells, the apoptosis rate was significantly higher than that by the two drugs individually. However, the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone. Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells. The Western blot results showed that the protein expression levels of the DR5, a-caspase-3, and BAX increased, while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells. Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells. CONCLUSION: The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment, which may ascribe to up-regulation of DR5.

A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5‐hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice‐burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved‐caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1‐type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) disease has been considered as the main cause of low back pain (LBP), which is a very common symptom and the leading cause of disability worldwide today. The pathological mechanism of IDD remains quite complicated, and genetic, developmental, biochemical, and biomechanical factors all contribute to the development of the disease. There exists no effective, non‐surgical treatment for IDD nowadays, which is largely related to the lack of knowledge of the specific mechanisms of IDD, and the lack of effective specific targets. Recently, non‐coding RNA, including miRNA, has been recognized as an important regulator of gene expression. Current studies on the effects of miRNA in IDD have confirmed that a variety of miRNAs play a crucial role in the process of IDD via nucleus pulposus cells (NPC) apoptosis, abnormal proliferation, inflammatory factors, the extracellular matrix (ECM) degradation, and annulus fibrosus (AF) degeneration. In the past 10 years, research on miRNA has been quite active in IDD. This review summarizes the current research progression of miRNA in the IDD and puts forward some prospects and challenges on non‐surgical treatment for IDD. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) is one of the most common health problems in people's lives, which brings a massive burden to clinicians, and the leading cause of LBP is intervertebral disc degeneration (IDD). IDD is mainly caused by factors such as aging, mechanical stress, and lack of nutrition. The pathological mechanism of IDD is very complex, involving inflammatory response, cell metabolism disorder, and so on. Unfortunately, in the current treatment of IDD, only relieving symptoms as the primary means of relieving a patient's pain cannot effectively inhibit or reverse the progression of IDD. Tumor necrosis factor-α (TNF-α) is a multifunctional pro-inflammatory factor involved in many diseases' pathological processes. With the in-depth study of the pathological mechanism of IDD, more and more evidence has shown that TNF-α is an essential activator of IDD, which is related to the metabolic disorder, inflammatory responses, apoptosis, and other pathological processes of extracellular dissociation in the intervertebral disc. Therefore, anti-TNF-α therapy is an effective therapeutic target for alleviating IDD, especially in inhibiting extracellular matrix degradation and reducing inflammatory responses. This article reviews the pathological role of TNF-α in IDD and the latest research progress of TNF-α inhibitors in treating IDD. • Summary of TNF-α and pathological mechanisms of Intervertebral Disc Degeneration and new research. • Discuss the relationship between TNF-α in intervertebral disc degeneration, NP cell apoptosis, pyroptosis and autophagy. • The figures in the article should give scholars who are new to this field a direct understanding of the mechanism. • It may be helpful to treat intervertebral disc degeneration with TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

The Jian-Yan-Ling (JYL) capsule is a famous anti-aging Chinese patent medicine. It is applied mainly to delay senescence to improve cognition in aging individuals. However, the action mechanisms of JYL for improving cognition have not been determined. We will evaluate the effect of the JYL capsule at improving the cognition of aging mice by improving oxidative stress in the hippocampus and exploring its action mechanism. A senescence mouse model was developed via intraperitoneal injection of D-galactose. The effect of the JYL capsule at improving the learning and memory abilities of mice was evaluated using the Morris water maze and novel object recognition tests. The apotosis of model mice hippocampus' were determined by TUNEL analysis. The antioxidant capacity of the JYL capsule was evaluated by determining the activities of antioxidant enzymes and expressions of oxidative products. The regulation of the Nrf2/HO-1 signaling pathway of the JYL capsule was evaluated by determining the expressions of related proteins via western blotting analysis. In vitro , H 2 O 2 -treated mouse hippocampal HT22 cells were used to evaluate the antioxidant capacity of JYL-containing rat serum by determining the cell viability, apoptotic level and expressions of related proteins. JYL capsules enhanced the learning and memory abilities of model mice according to behavioral tests. The results of TUNEL analysis showed that the JYL capsule ameliorated hippocampal apoptosis in model mice. JYL capsules also exerted significant antioxidant capacity by increasing the activities of antioxidant enzymes while decreasing the levels of oxidative products both in the hippocampus and serum. The regulation of Nrf2/HO-1 pathway might contribute to the antioxidant function. In vitro , JYL-containing rat serum protected HT22 cells from H 2 O 2 induced oxidative stress. The apoptosis of HT22 cells was also attenuated by regulating the caspase and Nrf2/HO-1 signaling pathways. The amelioration of neuronal oxidative stress of hippocampus might contribute to the D-galactose-induced cognition impairment of senescence mice. These findings provide evidence for the application of JYL capsules to enhance cognition in aging individuals. [Display omitted] [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP) and disability in the elderly, imposing significant public health and economic burden worldwide. Meanwhile, the pathological mechanisms of IDD remain complicated, and treatment strategy to reverse IDD is primarily due to the unclear specific mechanisms of IDD and the lack of particular effective targets. Interleukin-1β (IL-1β), one of the most important members of the IL-1 family, can induce solid pro-inflammatory activity by stimulating the secretion of various pro-inflammatory mediators and is considered the key to IDD mediator. However, in recent years, IL-1β is considered to be able to regulate IVD cell death in many ways, such as apoptosis, pyroptosis, ferroptosis, and so on. At the same time, numerous studies on IL-1β inhibitors suggest that inhibition of IL-1β may be a promising biological therapy for IDD. Many IL-1β inhibitors have been investigated through various pathogenic biological mechanisms, including inhibiting inflammatory processes, regulating ECM degradation, and more. Therefore, anti-IL-1β therapy may have the effect of alleviating disc degeneration. This article mainly reviews the mechanisms and functions of IL-1β in IDD and investigates advances in IL-1β inhibition as a promising biotherapeutic approach for disc degeneration. • The current article reviews the mechanisms and functions of IL-1β in IDD and investigates advances in IL-1β inhibition as a promising biotherapeutic approach for disc degeneration. We demonstrate function of IL-1β from different aspects, such as inflammatory responses, ECM metabolism, cell senescence, cell apoptosis, pyroptosis, and ferroptosis, oxidative stress, angiogenesis and neoinnervation in IDD. It is suitable for the audience of Experimental Gerontology, as IDD is a condition affecting the elderly. • This article could provide a valuable resource for researchers and clinicians seeking to better understand the role of IL-1β in IDD and explore potential therapeutic targets. • We provide a comprehensive review of the involvement of IL-1β in intervertebral disc degeneration (IVDD) and its potential as a therapeutic target. However, the article would benefit from a more detailed discussion on the differences between animal models and human in vivo experiments, as well as the potential limitations and challenges in translating these findings to human subjects. • We have presented several studies that show the promising effects of IL-1β inhibition in vitro and in animal models. However, the safety, reliability, and effectiveness of such treatments in humans remain uncertain. The article would benefit from a discussion of the challenges in conducting clinical trials for these treatments and the need for more extensive clinical studies in the future. • While we acknowledge the difficulty of studying intervertebral disc (IVD) tissue homeostasis, the review would benefit from a more in-depth exploration of the inflammatory process during IDD and its implications for the development of IL-1β-centered therapies. This may include a discussion of the role of inflammation in maintaining homeostasis and the potential risks of completely suppressing IL-1β-induced inflammation. • The article discusses the potential for IL-1β-centered therapy to restore homeostasis in the intervertebral disc. However, it would be beneficial for researchers and clinicians to provide more information on the current state of research in this area, including any promising drug candidates or novel approaches to treatment. [ABSTRACT FROM AUTHOR]

• The development of new therapeutic drug for SS treatment is urgent medical need. • Apoptosis, cycle arrest, intracellular ROS, mitochondria and autophagy were detected to identify effect of DATS on SS. • High-throughput RNA-sequencing analysis was performed to clarify a comprehensive molecular portrait for DATS-induced transcriptional regulation. • Go and KEGG analysis were performed to reveal the related molecular events induced by DATS pharmacological properties. • PPI network was conducted to identify hub genes and protein feature. Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein–protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS. [ABSTRACT FROM AUTHOR]