Colorectal cancer (CRC), a malignancy characterized by high aggressiveness, metastatic propensity, frequent recurrence, and poor prognosis, underscores the critical need for identifying biomarkers to guide targeted therapeutic strategies. Solute carrier family 38 member 5 (SLC38A5) emerges as a promising target due to its pharmacological tractability and role in cancer progression. In this study, we demonstrate that SLC38A5 promoted CRC progression through both bioinformatic analysis and experimental validation. Knockdown of SLC38A5 significantly suppressed cell viability, colony formation, and migratory ability in DLD1 and HCT116 cells. Notably, SLC38A5 depletion sensitized CRC cells to RSL3-induced ferroptosis. Mechanistically, SLC38A5 inhibition down-regulated antioxidant-related genes Nrf2 and Heme Oxygenase 1 (HO-1) and key ferroptosis regulators GPX4 and SLC7A11, while modulating Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) and Stearoyl-CoA Desaturase 1 (SCD1) expression. Additionally, SLC38A5 knockdown impaired nuclear translocation of YAP, the core transcriptional co-activator in the Hippo signaling pathway. ‌Chromatin immunoprecipitation (ChIP) analysis demonstrated the binding of YAP to Nrf2. Our findings reveal a novel mechanism wherein SLC38A5 confers ferroptosis resistance in CRC via YAP nuclear translocation within the Hippo signaling pathway. Collectively, this study highlights SLC38A5 as a potential therapeutic target to enhance ferroptosis-based cancer therapy, offering new strategies to improve CRC treatment outcomes.

Colorectal cancer (CRC) has emerged as the third most prevalent and second deadliest cancer worldwide. Metabolic reprogramming is a key hallmark of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) is over-expressed in multiple cancers, including CRC. Although the role of PHGDH in metabolism has been extensively investigated, its effects on CRC development remains to be elucidated. In the present study, it was demonstrated that PHGDH expression was significantly up-regulated in colorectal cancer. PHGDH expression was positively correlated with that of the aryl hydrocarbon receptor (AhR) and its target genes, CYP1A1 and CYP1B1, in CRC cells. Knockdown of PHGDH reduced AhR levels and activity, as well as the ratio of reduced to oxidized glutathione. The selective AhR antagonist stemregenin 1 induced cell death through reactive oxygen species-dependent autophagy in CRC cells. PHGDH knockdown induced CRC cell sensitivity to stemregenin 1 via the autophagy pathway. Our findings suggest that PHGDH modulates AhR signaling and the redox-dependent autophagy pathway in CRC, and that the combination of inhibition of both PHGDH and AhR may be a novel therapeutic strategy for CRC.

Amino acids act as versatile nutrients driving cell growth and survival, especially in cancer cells. Amino acid metabolism comprises numerous metabolic networks and is closely linked with intracellular redox balance and epigenetic regulation. Reprogrammed amino acid metabolism has been recognized as a ubiquitous feature in tumour cells. This review outlines the metabolism of several primary amino acids in cancer cells and highlights the pivotal role of amino acid metabolism in sustaining redox homeostasis and regulating epigenetic modification in response to oxidative and genetic stress in cancer cells.

The solute carrier (SLC) family, with more than 400 membrane-bound proteins, facilitates the transport of a wide array of substrates such as nutrients, ions, metabolites, and drugs across biological membranes. Amino acid transporters (AATs) are membrane transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, redox regulation, and neurological regulation. Several AATs have been found to significantly impact the progression of human malignancies, and dysregulation of AATs results in metabolic reprogramming affecting tumor growth and progression. However, current clinical therapies that directly target AATs have not been developed. The purpose of this review is to highlight the structural and functional diversity of AATs, the molecular mechanisms in human diseases such as tumors, kidney diseases, and emerging therapeutic strategies for targeting AATs.

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death and has been implicated in the occurrence and development of various diseases, including heart disease, nervous system diseases and cancer. Ferroptosis induction recently emerged as an attractive strategy for cancer therapy. Ferroptosis has become a potential target for intervention in these diseases or injuries in relevant preclinical models. This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer, highlights redox status and metabolism's role in it. Combination therapy for ferroptosis has great potential in cancer treatment, especially malignant tumors that are resistant to conventional therapies. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy. A deeper understanding of the relationship between ferroptosis resistance and metabolism reprogramming may provide new strategies for tumor treatment and drug development based on ferroptosis.

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial–mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and major cause of cancer death in the world. Ferroptosis is a recently identified type of regulated cell death. Increasing evidence has shown that ferroptosis plays an important regulatory role in the occurrence and development of cancer. This study identified TIGAR as a potential regulator of ferroptosis resistance in the development of CRC. We showed that TIGAR expression in CRC tissues is significantly higher than that in adjacent normal tissues. Knockdown of TIGAR significantly caused an increase in erastin-induced ferroptosis in SW620 and HCT116 cells. Notably, knockdown of TIGAR significantly decreased GSH/GSSG ratio, increased lipid peroxidation production, and facilitated the accumulation of lipid peroxidation product malondialdehyde (MDA), and rendered CRC cells more sensitive to erastin induced ferroptosis. Furthermore, TIGAR inhibition repressed SCD1 expression in a redox and AMPK-dependent manner. Thus, these results suggest that TIGAR induces ferroptosis resistance in CRC cells via the ROS/AMPK/SCD1 signaling pathway.

Breast cancer has become the first rank cancer in the world,and the exploration of the pathogenesisand treatment of breast cancer deserves more and more attention.Lipid metabolism dysfunction is one of the mostprominent metabolic changes in cancer cells.It is very important to explore the changes of lipid metabolism inbreast cancer cells in order to find new diagnostic indicators and therapeutic targets.This paper introduces theresearch progress of lipid metabolism dysfunction in breast cancer from4aspects:(1)the expression of abnormalfatty acid metabolism in breast cancer from three aspects of fatty acid synthesis,oxidation and uptake and therelated research progress;(2)introduction to the abnormal expression of triglyceride metabolism in breast cancerfrom the aspects of triglyceride synthesis and degradation and the related research progress;(3)to introduce theabnormal expression of cholesterol synthase in breast cancer and the related research progress;(4)to introducethe abnormal expression of lipid metabolism signaling pathways in breast cancer from five signaling pathways,namely Notch,Hippo,Hedgehog,Wnt and mTOR,and the related research progress.The aim is to provide newideas and methods for targeting lipid metabolism in the treatment of breast cancer

Superhydrophobic surfaces are important in many applications owing to their special properties such as self-cleaning, anti-icing, antibacterial, and anti-fogging. In this paper, a micro/nano hierarchical superhydrophobic surface with a low roll-off angle was created on 304 stainless steel. The water contact angle was measured to be 152° with a roll-off angle of 7.3°. Firstly, microscale bumps were created by femtosecond laser irradiation. Secondly, zinc oxide (ZnO) nanowires were fabricated on the laser-induced bumps using a hydrothermal synthesis method. Results show that after laser treatment and ZnO nanostructuring, the stainless steel surface became superhydrophobic. However, the roll-off angle of this hierarchical structure surface was larger than 90°. To reduce the surface activity, trimethoxy silane hydrophobic coating was applied. A 7.3° roll-off angle was achieved on the coated surface. The underlying mechanism was discussed. The hydrophobic ZnO structured surface can help prevent bacterial contamination from water, which is important for implants. Thus, for biomedical applications, the antibacterial property of this hierarchical surface was examined. It was found that the antibacterial property of sample surfaces with ZnO nanowires were significantly increased. The optical density (OD) of Escherichia coli (E. coli) attached to the original surface was 0.93. For the micro-structured surface (with bumps), the OD was 0.9, and for the hierarchical surface (with bump & nanowires), it was 0.54. For nanostructured ZnO nanowire surface, the OD was only 0.09. It demonstrates good antibacterial properties of ZnO nanowires.

Background: Abnormal Cu(II) ions levels may affect many biological functions, and it is of great importance to detect Cu(II) ions in organisms. Methods: Herein, we report a near-infrared (NIR) fluorescent probe EtRh-N-NH𝟐 for the detection of Cu(II). In the probe structure, a rhodamine core was used, and a hydrazine group was employed as the responsive site. Results & Conlusions: EtRh-N-NH𝟐 displayed sensitive, specific and fast response upon Cu(II) with excellent linear relationship between the concentration and fluorescence emission intensity in 0–1 μM range. The releasing EtRh-COOH exhibited 762 nm of emission wavelength with a 75 nm of Stokes shift.

Cancer cells can metabolize glutamine to replenish TCA cycle intermediates for cell survival. Glutaminase (GLS1) is over-expressed in multiple cancers, including colorectal cancer (CRC). However, the role of GLS1 in colorectal cancer development has not yet fully elucidated. In this study, we found that GLS1 levels were significantly increased in CRC cells. Knockdown of GLS1 by shRNAs as well as GLS1 inhibitor BPTES decreased DLD1 and SW480 cell proliferation, colony formation and migration. Knockdown of GLS1 as well as BPTES induced reactive oxygen species (ROS) production, down-regulation of GSH/GSSG ratio, an decrease in Nrf2 protein expression and an increase in cytoplasmic Nrf2 protein expression in DLD1 and SW480 cells. Furthermore, Knockdown of GLS1 as well as BPTES inhibited autophagy pathway, antioxidant NAC and Nrf2 activator could reversed inhibition of GLS1-mediated an decrease in autophagic flux in DLD1 and SW480 cells. Depletion of GLS1-induced inhibition of DLD1 and SW480 CRC cell proliferation, colony formation and migration was reversed by autophagy inducer rapamycin. These results suggest that targeting GLS1 might be a new potential therapeutic target for the treatment of CRC.

课程思政是新时期高校教育新模式.如何充分发掘医学基础专业基础课程蕴含的课程思政元素,将其融入教学实践过程中,对实现三全育人,引导学生建立正确的人生观、价值观及职业观,具有重要的现实意义.通过对医学基础的课程思政元素和教案设计进行探索与实践,设计医学基础课程思政的切入点、思路.通过教学实践与教学反思,准确地把握思想政治教育的时机与方法.主要探索课程思政与医学基础课程的有效融合教学范式,发挥立德树人和三全育人的重要作用.

如何充分发掘药理学专业基础课程所蕴含的课程思政元素,将其融入日常教学,对实现三全育人,引导当代大学生建立正确人生观、价值观及职业观,具有重要的现实意义.本文主要从探索课程思政与药理学专业课程的有效融合教学范式,发挥立德树人和三全育人的重要作用.

线上线下混合式教学成为实现大学教育教学新形态.结合药理学线上教学与传统线下课堂教学的特点,探讨了基于慕课异步SPOC课程的特点及其与传统教学模式相融合的混合式教学模式的探索,包括教学平台的选择、教学的组织和特点、教学的考核等,分析了线上线下混合式教学模式的新特点,旨在促进线上教学与传统教学在药理学课堂中的应用,为传统教学提供了新的活力.

Breast cancer has the highest incidence and mortality in the female population. Forkhead box M1 (FOXM1) known as a transcription factor is upregulated and associated with poor prognosis in a variety of cancers. However, the molecular mechanisms of FOXM1 on breast cancer progression are poorly understood. In this study, we found that FOXM1 was up-regulated in breast cancer. FOXM1 promoted cell proliferation, clonal formation, and migration capacity in triple negative breast cancer by increasing transcriptional activity of YAP1. FOXM1 also maintained cell stemness via the Hippo pathway. The YAP1-TEAD binding inhibitor Verteporfin reduced the transcription level of OCT4 and NANOG but the Hippo pathway activator XMU-MP-1 could increase the transcription level of OCT4 and NANOG. In summary, our findings indicated that FOXM1 promoted breast cancer progression through the Hippo pathway, and it was suggested a new strategy to treat breast cancer.

培养学生自主学习与创新能力是高等教育的重要任务.药理学课程内容烦琐以及概念抽象成为教学难点.在药理学教学过程中,引入FDA最新批准的新药研讨式教学作为创新性教学方法,将"以学生为中心"的教育理念渗透到药理学教学的全过程,提出了自主学习理念下的药理学混合教学策略.该方法提高了教学效果,提高了学生学习药理学的积极性,培养了学生自主学习能力和创新性思维能力,增强了学生科研兴趣,培养了学生的团队协作意识.

AIMS:Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality worldwide. Over-expression of tetraspanin 8 (TSPAN8) is related to the development and progression of CRC. Whether TSPAN8 plays a role in the growth of colorectal cancer and its epigenetic mechanisms regulated by Lysine Specific Demethylase 1 (LSD1) are still unknown.MAIN METHODS:In this study, RT-PCR and western blotting were used to analyze the mRNA and protein expression, respectively; cell viability was assayed with MTS analysis; cell migration was measured with Trans-well analysis.KEY FINDINGS:In the present study, the results indicated that the mRNA levels of LSD1 and TSPAN8 in CRC were significantly higher than that in corresponding adjacent non-tumor tissue. Down-regulation of LSD1 or TSPAN8 as well as LSD1 inhibitor Tranylcypromine hemisulfate inhibited the proliferation and migration of CRC cells, while over-expression of LSD1 exhibited opposite effects. LSD1 up-regulated TSPAN8 expression and reduced H3K9me2 occupancy on the TSPAN8 promoter in CRC cells. TSPAN8 promoted epithelial-mesenchymal transition (EMT) in CRC cells in LSD1-dependent manner.SIGNIFICANCE:TSPAN8 may be considered as a promising biomarker for the diagnosis and prognosis in patients with CRC. Furthermore, TSPAN8 could be a novel therapeutic target and potent LSD1 inhibitors could be designed and developed in the treatment of CRC.

在肿瘤发生过程中,组蛋白赖氨酸去甲基化酶(LSD1)的表达失调是一个重要标志.LSD1能够于组蛋白H3的N端与H3K4me2/1和H3K9me2/1相互作用,并使其去甲基化,从而调控多种不同的生理过程.同时,LSD1表达水平变化还与多种基因如p53、DNMT1和EZH2等的表达水平相关联,在胚胎发育、细胞分化和肿瘤增殖转移过程中起重要作用.

Objective To observe the proliferation ability of NIH/3T3 cells after a long-term exposure to 1800 MHz electromagnetic radiation.Methods Cells were exposed to 1800 MHz electromagnetic radiation,at SAR of 2 W/kg,intermittently exposure mode (5 min on/10 min off),5 h/d.Then plate clone forming test and soft agar clone forming test of the exposed and sham exposed cells were cultured respectively after 60-day and 138-day exposure.Telomerase expressions of each group were detected by ELISA.Results In plate clone experiments,plate clone forming ratio was significantly lowcr than that of the sham group (P＜O.05) after 60-day exposure,however,there was no significant difference between the exposed cells and the sham after 138-day exposure.In soft agar clone experiments,soft agar clone forming was no significantly different from sham group after 60-day exposure,however,138-day exposure group formation was significantly higher than that of the sham group (P＜0.05).In telomerase experiments,after 60 days of exposure,the expression of telomerase was no significantly different from sham group,whereas 138-day exposure group was significantly higher than sham group (P ＜ 0.05).Conclusions 1800 MHz electromagnetic radiation could damage the proliferation of NIH/3T3 cells exposed for 60 days,whereas the ability of cell transformation and proliferation increased significantly after more long-term exposure (138 days).

转移侵袭是恶性肿瘤的基本特征和重要标志,也是导致患者死亡的最主要原因.研究表明,超过80％的恶性肿瘤患者最终死于肿瘤转移.本文综述了DNA甲基化、DNA羟甲基化、组蛋白修饰等表观遗传机制在上皮间质转化中的作用机制,以及肿瘤转移相关信号通路在上皮间质转化中的研究进展.其机制的阐明有可能为肿瘤治疗提供新的方向.