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Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.

This study aimed to explore the underlying mechanism of linc01014 in oesophagus cancer gefitinib resistance. Gefitinib‐resistant oesophagus squamous cell carcinoma (ESCC gefitinibR) cell lines were constructed by using different gefitinib treatment in FLO‐1, KYAE‐1, TE‐8 and TE‐5 cell lines and confirmed by MTS50 and proliferation assays. Expression of linc01014 was overexpressed/silenced in FLO‐1 cells followed by gefitinib treatment, and then, the apoptosis‐associated markers Bax and Bcl‐2, and PI3KCA in PI3K signalling pathway were determined using Western blotting. MST50 and morphology analyses showed that ESCC gefitinibR cell lines presented obvious gefitinib resistance than their parental ESCC cell lines. ESCC gefitinibR cell lines showed significantly higher proliferation abilities than their parental ESCC cell lines after treating with gefitinib. Overexpression of linc01014 significantly inhibited the apoptosis of FLO‐1 cells induced by gefitinib and silencing linc01014 obviously promoted the apoptosis of FLO‐1 cells induced by gefitinib. Silencing linc01014 could significantly increase the gefitinib chemotherapy sensitivity of oesophagus cancer via PI3K‐AKT‐mTOR signalling pathway.

Objectives The purpose of this study was to investigate the treatment effect and molecular mechanism of tetrahedral framework nucleic acids (tFNAs), novel self‐assembled nucleic acid nanomaterials, in diffuse BMEC injury after SAH. Materials and Methods tFNAs were synthesized from four ssDNAs. The effects of tFNAs on SAH‐induced diffuse BMEC injury were explored by a cytotoxicity model induced by hemin, a breakdown product of hemoglobin, in vitro and a mouse model of SAH via internal carotid artery puncture in vivo. Cell viability assays, wound healing assays, transwell assays, and tube formation assays were performed to explore cellular function like angiogenesis. Results In vitro cellular function assays demonstrated that tFNAs could alleviate hemin‐induced injury, promote angiogenesis, and inhibit apoptosis in hemin cytotoxicity model. In vivo study using H&E and TEM results jointly indicated that the tFNAs attenuate the damage caused by SAH in situ, showing restored number of BMECs in the endothelium layer and more tight intercellular connectivity. Histological examination of SAH model animals confirmed the results of the in vitro study, as tFNAs exhibited treatment effects against diffuse BMEC injury in the cerebral microvascular bed. Conclusions Our study suggests the potential of tFNAs in ameliorating diffuse injury to BMECs after SAH, which laid theoretical foundation for the further study and use of these nucleic acid nanomaterials for tissue engineering vascularization. The potential of tFNAs in ameliorating diffuse injury to BMECs after SAH, laying a theoretical foundation for the further study and the use of these nucleic acid nanomaterials.

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI 3 K Ser294 /T-PI 3 K, P-Akt Ser473 /T-Akt, and P-mTOR Ser2448 /T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI 3 K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI 3 K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.

Ozone injection is generally used for the management of pain in diseases such as osteoarthritis (OA). Recent studies have shown that reduced autophagy in chondrocytes plays an important role in the development of OA. The purpose of this study was to determine whether ozone treats OA by inducing autophagy in OA chondrocytes. In this study, primary chondrocytes were stimulated with IL-1β for 24 hours to simulate an OA chondrocyte model, followed by treatment with ozone (30 µg/ mL) or pretreatment with 3-methyladenine or compound C before ozone treatment. Then, cell viability was detected by a CCK-8 kit, and the AMPK/mTOR signaling pathway and autophagy were detected by Western blotting and immunofluorescence. The mRNA expression levels of IL-6, TNF-α, MMP-13 and TIMP-1 were measured by quantitative real-time PCR. Finally, autophagosomes in chondrocytes were observed by transmission electron microscopy. Ozone improved cell viability in chondrocytes stimulated by IL-1β. The decreased level of autophagy in IL-1β-stimulated chondrocytes improved with ozone treatment through activation of the AMPK/mTOR signaling pathway. In addition, the mRNA expression levels of IL-6 and TNF-α were suppressed by ozone treatment in chondrocytes stimulated with IL-1β. Ozone increased the mRNA level of TIMP-1 and decreased the mRNA level of MMP-13 in chondrocytes stimulated with IL-1β. These results suggested that ozone improved the decreased level of autophagy in chondrocytes stimulated with IL-1β through activation of the AMPK/mTOR signaling pathway. Moreover, ozone treatment suppressed inflammation and helped maintain metabolic balance in chondrocytes stimulated with IL-1β.

Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs. This study demonstrates a multimodal mechanism of spider toxin Lycosin‐I, which exhibits selective and effective treatment of leukemia. Lycosin‐I exhibits membrane lysis, particularly at high concentrations and triggers apoptosis, cell cycle arrest and ferroptosis by suppressing PI3K‐AKT‐mTOR signaling pathway. These findings deepen the understanding of the inhibitory mechanisms of anticancer peptides and Lycosin‐I can be a promising lead for leukemia therapy.

MicroRNAs (miRNAs) are strongly associated to the progression of hepatocellular carcinoma (HCC), which presents a high potential for diagnosis and treatment; however, the role of miRNAs is still largely unknown. The aim of the present study was to examine the expression and the biological role of miRNA (miR)-206 in the development of HCC, and to identify the underlying molecular mechanism. Results from this study show that miR-206 was significantly downregulated in HCC tissues and cell lines. It was observed that low expression of miR-206 was linked to advanced TNM stage, tumor nodularity and venous infiltration in patients with HCC; low miR-206 expression was associated with shorter survival times. miR-206 overexpression using miR-206 mimics notably decreased the proliferative ability and increased apoptosis of MHCC97-H and HCCLM3 HCC cell lines. Overexpression of miR-206 suppressed invasiveness associated with reduced epithelial-mesenchymal transition. Moreover, the c-Met oncogene, which is upregulated in HCC tissues, was negatively associated with the expression of miR-206. Notably, it was shown that miR-206 may exert its antitumor effect through suppressing c-Met/Akt/mTOR signaling. Low expression of miR-206 was shown to be regulated by lncRNA MALAT1 in HCC. Collectively, this study presented evidence that miR-206 was controlled by lncRNA MALAT1 and partially suppressed the proliferation and invasion of HCC through the c-Met/Akt/mTOR signaling pathway. According to these results, understanding MALAT1/miR-206-dependent regulation may lead to potential approaches for diagnosis and prospective treatment of HCC.

Objective Stearoyl‐coenzyme A desaturase 1 (SCD1) is a key enzyme in fatty acid metabolism and has been implicated in cancer progression, including head and neck squamous cell carcinoma (HNSCC). The phosphoinositide 3‐kinase (PI3K)‐AKT‐mammalian target of rapamycin (mTOR) signaling pathway is a critical regulator of cellular metabolism and survival in cancer. This study investigates the crosstalk between SCD1 inhibition and the PI3K‐AKT‐mTOR pathway, highlighting the therapeutic potential of targeting SCD1 in HNSCC. Study Design Basic science. Setting Laboratory. Methods Four HNSCC cell lines were utilized to evaluate the relationship between SCD1 and the mTOR signaling pathway. Cell viability was assessed following treatment with various mTOR inhibitors. The effect of AKT‐mTOR signaling on SCD1 expression was examined through pharmacological inhibition and gene silencing approaches. Additionally, the impact of SCD1 knockdown on cell proliferation and survival was analyzed. Results mTOR inhibitors significantly reduced HNSCC cell viability and downregulated SCD1 expression in a dose‐dependent manner. Inhibition of AKT, a key upstream effector of mTOR, also suppressed SCD1 expression, suggesting that SCD1 is regulated through the PI3K‐AKT‐mTOR axis. Silencing SCD1 independently impaired cancer cell growth and enhanced the cytotoxic effects of mTOR inhibitors, indicating a synergistic anticancer effect. Conclusion SCD1 is a downstream target of the PI3K‐AKT‐mTOR pathway and contributes to HNSCC cell survival. Dual targeting of SCD1 and the mTOR signaling pathway represents a promising therapeutic strategy for HNSCC treatment. Further investigation is warranted to explore the clinical potential of SCD1 inhibitors in combination with mTOR‐targeted therapies.

Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPK-mTOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1. In this study, we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-mTOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. Rats were intraperitoneally injected with puerarin, 50 or 100 mg/kg, daily for 7 days. Then, 30 minutes after the final administration, rats were subjected to transient middle cerebral artery occlusion for 90 minutes. Then, after 24 hours of reperfusion, the Longa score and infarct volume were evaluated in each group. Autophagosome formation was observed by transmission electron microscopy. LC3, Beclin-1 p62, AMPK, mTOR and ULK1 protein expression levels were examined by immunofluorescence and western blot assay. Puerarin substantially reduced the Longa score and infarct volume, and it lessened autophagosome formation in the hippocampal CA1 area following cerebral ischemia/reperfusion injury in a dose-dependent manner. Pretreatment with puerarin (50 or 100 mg/kg) reduced Beclin-1 expression and the LC3-II/LC3-I ratio, as well as p-AMPK and pS317-ULK1 levels. In comparison, it increased p62 expression. Furthermore, puerarin at 100 mg/kg dramatically increased the levels of p-mTOR and pS757-ULK1 in the hippocampus on the ischemic side. Our findings suggest that puerarin alleviates autophagy by activating the APMK-mTOR-ULK1 signaling pathway. Thus, puerarin might have therapeutic potential for treating cerebral ischemia/reperfusion injury.