International Journal of Biochemistry & Cell Biology最新文献_第5页

SPDYE3 promotes cell cycle and LUSC progression by regulating the CDC25C/CDK1 pathway SPDYE3通过调节CDC25C/CDK1通路促进细胞周期和LUSC进展

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-26 DOI: 10.1016/j.biocel.2025.106825

Zhuowei Shao , Jiankui Ye , Yili Wu , Yu Chen , Rong Wang , Shuai Fang , Shibo Wu

Background

Lung cancer is the primary reason for global cancer-related deaths. Targeted therapy is currently absent for lung squamous cell carcinoma (LUSC), a significant pathological subtype of lung cancer. The gene SPDYE3, a member of the Speedy/Ringo gene family, is highly expressed in different cancer tissues and functions as a cell cycle regulator. However, the potential mechanisms and clinical significance of SPDYE3 in LUSC remain unknown.

Method

Gene chip technology was used to detect the expression profiles of RNA in saliva, plasma, and normal controls of LUSC patients. Real-time quantitative polymerase chain reaction(qRT-PCR) was utilized to examine the expression and significance of SPDYE3 in the early diagnosis of LUSC. Furthermore, additional experiments were performed in vitro and in vivo to further assess the impact of SPDYE3 on the proliferation and cell cycle of LUSC. Further investigations were performed using IP, mass spectrometry analysis, and Western blotting to explore the interaction between SPDYE3 and cell division cycle 25 C (CDC25C).

Result

Our data showed that SPDYE3 is upregulated in LUSC tissues, plasma, and cells. SPDYE3 exhibited diagnostic usefulness, achieving an Area Under the Curve (AUC) of 0.7288. Experiments conducted in vitro and in vivo revealed that SPDYE3 enhances the growth and advancement of the cell cycle in LUSC cells. SPDYE3 mechanistically stimulates the activation of cyclin-dependent kinase 1 (CDK1) and controls the advancement of the cell cycle by interacting with CDC25C.

Conclusion

Overall, our results support the novel regulatory role of SPDYE3 in LUSC cell cycle progression mechanisms by influencing the CDC25C/CDK1 signaling pathway.

肺癌是全球癌症相关死亡的主要原因。肺鳞状细胞癌（LUSC）是一种重要的肺癌病理亚型，目前缺乏靶向治疗。spdye基因是Speedy/Ringo基因家族的一员，在不同的癌症组织中高度表达，并具有细胞周期调节作用。然而，SPDYE3在LUSC中的潜在机制和临床意义尚不清楚。方法采用基因芯片技术检测LUSC患者唾液、血浆及正常对照中RNA的表达谱。采用实时定量聚合酶链反应（Real-time quantitative polymerase chain reaction, qRT-PCR）检测SPDYE3在LUSC早期诊断中的表达及意义。此外，我们还进行了体外和体内实验，进一步评估SPDYE3对LUSC增殖和细胞周期的影响。利用IP、质谱分析和Western blotting进一步研究SPDYE3与细胞分裂周期25 C （CDC25C）之间的相互作用。结果SPDYE3在LUSC组织、血浆和细胞中表达上调。SPDYE3具有诊断价值，曲线下面积（AUC）为0.7288。体外和体内实验表明SPDYE3能促进LUSC细胞的生长和细胞周期的推进。SPDYE3通过与CDC25C相互作用，刺激细胞周期蛋白依赖性激酶1 （cyclin-dependent kinase 1, CDK1）的活化，控制细胞周期的推进。总之，我们的研究结果支持SPDYE3通过影响CDC25C/CDK1信号通路在LUSC细胞周期进程机制中的新调控作用。

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引用次数: 0

27P silk bioactive peptides mediate multifaceted regulation of collagen and support balance in fibroblast subpopulations p丝生物活性肽介导成纤维细胞亚群胶原蛋白和支持平衡的多方面调节。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-19 DOI: 10.1016/j.biocel.2025.106821

SaiLavanyaa Sundar, Marios Frantzeskos Sardis, Lior Artzi, Aneesha Polisety, Setu Vora, Greg Altman, Svetlana Marukian

Fibroblasts play a key role in maintaining skin structure and immune balance, but factors like aging, stress, and chronic inflammation can weaken their function, leading to collagen loss, thinning skin, and increased inflammation. Traditional collagen boosters like retinoic acid (RA), vitamin C (VC), hyaluronic acid (HA), and transforming growth factor beta (TGFβ) have drawbacks, including poor absorption, instability, and irritation.

Studies reveal that Silk Bioactive Peptide (27 P peptide) binds to epidermis and dermal fibroblasts, enhancing prolonged pro-collagen 1 (pro-C1) secretion in 3D and 2D models. De-novo collagen synthesis by 27 P peptide, likely regulated at the translational level, resulted in elevated collagen deposition and matrix remodeling up to 120 h. Combination of VC and 27 P peptide rescues VC-induced intracellular collagen depletion. Unlike TGFβ and RA, 27 P peptide maintains balance between fibroblast subpopulations, without inducing markers of fibrosis or inflammation. Together, 27 P peptide presents as a promising alternative to effectively promote collagen production, fibroblast homeostasis and skin health.

成纤维细胞在维持皮肤结构和免疫平衡方面发挥着关键作用，但衰老、压力和慢性炎症等因素会削弱它们的功能，导致胶原蛋白流失、皮肤变薄和炎症增加。传统的胶原蛋白促进剂，如维甲酸（RA）、维生素C （VC）、透明质酸（HA）和转化生长因子β (TGFβ)都有缺点，包括吸收差、不稳定和刺激。研究发现，在3D和2D模型中，丝绸生物活性肽（27P肽）与表皮和真皮成纤维细胞结合，延长了原胶原1 （pro-C1）的分泌。27P肽的De-novo胶原合成可能在翻译水平受到调节，导致胶原沉积和基质重塑升高至120h。VC和27P肽联合使用可挽救VC诱导的细胞内胶原耗竭。与TGFβ和RA不同，27P肽维持成纤维细胞亚群之间的平衡，不诱导纤维化或炎症标志物。总之，27P肽是有效促进胶原蛋白生成、成纤维细胞稳态和皮肤健康的一种有前景的替代方法。

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引用次数: 0

Sepsis impairs immunocompetent plasmacytoid dendritic cell reconstitution from hematopoietic stem/progenitor cell through altered bone marrow environment 脓毒症通过改变骨髓环境损害造血干细胞/祖细胞的免疫能力浆细胞样树突状细胞重建。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-19 DOI: 10.1016/j.biocel.2025.106823

Jie Lu , Zhuo Lv , Meizhu xue , Dan Fan , Huiping Yang , Yi Hong , Yichen Wang , Zhangqiang Guo , Jiajun Ma , Jie Huang , Lijun Meng , Shuiyan Wu , Zhenjiang Bai

Plasmacytoid dendritic cells (pDCs) are crucial components of the immune response during viral infections, yet their function and development in the late phase of sepsis remain poorly understood. In this study, we investigated the impact of prolonged sepsis on pDCs and their progenitors in cecal ligation and puncture (CLP)-induced septic mice. We observed a significant reduction in both pDCs and their progenitors, alongside the presence of mature and regulatory pDCs. These mature and regulatory pDCs exhibited impaired type I interferon (IFN) secretion and antigen presentation capacity. In a Flt3L culture system of hematopoietic stem/progenitor cells (HSPCs) from CLP and Sham mice, we found that CLP-derived HSPCs exhibited an impaired ability to generate immunocompetent pDCs, as evidenced by lower IFN-α expression and reduced pDC recovery. Further investigation revealed downregulation of the key transcription factor TCF4 during pDC differentiation in these progenitor cells. Ectopic expression of TCF4 in these progenitors restored pDC generation. Additionally, we observed elevated levels of granulocyte colony-stimulating factor (G-CSF) in the bone marrow supernatant of septic mice. The addition of G-CSF to the culture system significantly impaired the generation of immunocompetent pDCs from HSPCs of normal mice. These findings suggest that sepsis may impair the production of immunocompetent pDCs from HSPCs by modulating key genes involved in pDC differentiation, potentially contributing to immune suppression and increased susceptibility to opportunistic infections in the later stages of sepsis.

浆细胞样树突状细胞（pDCs）是病毒感染期间免疫反应的重要组成部分，但其在败血症晚期的功能和发育尚不清楚。在这项研究中，我们研究了长期脓毒症对盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠pDCs及其祖细胞的影响。我们观察到pDCs及其祖细胞的显著减少，以及成熟和调节性pDCs的存在。这些成熟的调节性pDCs表现出I型干扰素（IFN）分泌和抗原递呈能力受损。在CLP和Sham小鼠造血干细胞/祖细胞（HSPCs）的Flt3L培养系统中，我们发现CLP衍生的HSPCs产生免疫活性pDCs的能力受损，IFN-α表达降低，pDC恢复减少。进一步的研究发现，在这些祖细胞的pDC分化过程中，关键转录因子TCF4下调。TCF4在这些祖细胞中的异位表达恢复了pDC的生成。此外，我们观察到脓毒症小鼠骨髓上清液中粒细胞集落刺激因子（G-CSF）水平升高。在培养系统中加入G-CSF可显著抑制正常小鼠HSPCs产生具有免疫能力的pDCs。这些发现表明，脓毒症可能通过调节参与pDC分化的关键基因，损害HSPCs产生具有免疫能力的pDC，可能导致脓毒症后期免疫抑制和增加对机会性感染的易感性。

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引用次数: 0

Retraction notice to "Activation-induced internalization differs for the tetraspanins CD9 and Tspan8: Impact on tumor cell motility" [Intern. J. Biochem. Cell Biol., 43/1 (2011) 106–119] 对“激活诱导的四跨蛋白CD9和Tspan8的内化不同：对肿瘤细胞运动的影响”的撤回通知[实习生]。学生物化学j。细胞生物。， 43/1(2011) 106-119]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-16 DOI: 10.1016/j.biocel.2025.106818

Sanyukta Rana , Christoph Claas , Cosima C. Kretz , Irina Nazarenko , Margot Zoeller

引用次数: 0

METTL5-mediated m6A modification of SLC7A11 promotes cervical cancer by inhibiting ferroptosis mettl5介导的m6A修饰SLC7A11通过抑制铁下垂促进宫颈癌。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-15 DOI: 10.1016/j.biocel.2025.106822

Yujin Dong, Wei Chang, Bei Lu, Yuanyuan Li, Yuanhua Liu

Ferroptosis could suppress the viability of cervical cancer cells and trigger their death, thereby offering a unique perspective for exploring novel therapeutic approach for cervical cancer. Here, this study tried to explore the role of N⁶-methyladenosine (m⁶A) methyltransferase methyltransferase-like 5 (METTL5) on cervical cancer ferroptosis. Elevated METTL5 functioned as an oncogene in cervical cancer tumorigenesis by inhibiting the ferroptosis. Mechanistically, METTL5 was verified to target SLC7A11 and installed the m⁶A methylation on SLC7A11 mRNA. Moreover, YTHDF3 bound with the m⁶A site of SLC7A11 mRNA to enhance SLC7A11 mRNA stability. Rescue assays confirmed that METTL5/YTHDF3/SLC7A11 axis inhibited the ferroptosis of cervical cancer cells. In vivo, METTL5 silencing repressed the tumor growth of cervical cancer cells, as well as reducing the SLC7A11. In conclusion, these data inspired that METTL5-mediated m⁶A modification of SLC7A11 promoted cervical cancer by inhibiting ferroptosis, providing a novel insight for cervical cancer.

铁下垂可以抑制宫颈癌细胞的活力并引发其死亡，从而为探索宫颈癌的新治疗方法提供了独特的视角。本研究试图探讨n6 -甲基腺苷（m6A）甲基转移酶-甲基转移酶样5 （METTL5）在宫颈癌铁下垂中的作用。升高的METTL5通过抑制铁下垂在宫颈癌的肿瘤发生中发挥致癌基因的作用。在机制上，METTL5被证实靶向SLC7A11，并将m6A甲基化安装在SLC7A11 mRNA上。此外，YTHDF3结合SLC7A11 mRNA的m6A位点，增强SLC7A11 mRNA的稳定性。挽救实验证实METTL5/YTHDF3/SLC7A11轴抑制子宫颈癌细胞铁下垂。在体内，METTL5沉默抑制了宫颈癌细胞的肿瘤生长，并降低了SLC7A11。综上所述，这些数据启发了mettl5介导的m6A修饰SLC7A11通过抑制铁下垂促进宫颈癌，为宫颈癌提供了新的见解。

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引用次数: 0

Maternal high-fat diet-induced obesity in offspring: Unraveling adipose tissue dysfunction mediated by increased heat shock proteins 母亲高脂肪饮食诱导的后代肥胖：通过增加热休克蛋白介导的脂肪组织功能障碍

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-11 DOI: 10.1016/j.biocel.2025.106812

Henry A. Paz , Lasya Buddha , Tianfu Lam , Ying Zhong , James D. Sikes , Kartik Shankar , Aline Andres , Umesh D. Wankhade

Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring. In established adipocyte cell lines independent of experimental animals, the expression of HSPs during differentiation was higher in white than in brown adipocytes. Also, expression of Hsp90ab1 in human umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male, but not in female infants. This finding was generated independently of the animal model and were intended to strengthen the translational perspective of our work. Together, these results suggest a potential link between maternal diet, HSPs, and adipose tissue function.

孕妇孕前和怀孕期间的体重和饮食对后代的代谢健康有重大影响，尽管对孕妇营养过剩在代谢和脂肪组织适应方面的性别差异仍未充分了解。本研究利用母体高脂肪饮食诱导肥胖小鼠模型，评估了性别二态性对后代肥胖、生理和脂肪组织功能的影响。与雌性后代相比，HF饲粮喂养的雄性后代表现出更大的体重增加和肥胖，葡萄糖稳态受损，血清胰岛素、瘦素和胆固醇水平升高，白色脂肪组织中脂肪生成和热休克蛋白（HSPs）基因表达增加。在独立于实验动物的已建立的脂肪细胞系中，在分化过程中，白色脂肪细胞的热休克蛋白表达高于棕色脂肪细胞。此外，Hsp90ab1在人脐带间质干细胞中的表达倾向于在男性婴儿中与母亲体重指数呈正相关，而在女性婴儿中则没有。这一发现是独立于动物模型产生的，旨在加强我们工作的翻译视角。总之，这些结果表明母亲的饮食、热蛋白和脂肪组织功能之间存在潜在的联系。

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引用次数: 0

Cofilin is a key regulator of oxidative stress-induced intercellular tunneling nanotubes formation Cofilin是氧化应激诱导的细胞间隧道纳米管形成的关键调节因子

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-09 DOI: 10.1016/j.biocel.2025.106820

Hongce Chen , Zhirui Wu , Lingyu Wang, Jingyao Zeng, Tongsheng Chen

Tunneling nanotubes (TNTs) are open membranous channels between connected cells, TNTs-mediated substance transfer between tumor cells plays an important role in drug resistance, metastasis and recurrence of tumors. This study aims to explore the composition of TNTs between tumor cells and the function of cofilin in TNTs formation. Oxidative stress induces the formation of TNTs between tumor cells. The components of TNTs include microfilaments and cell membranes, some of which contain microtubules, as well as mitochondria, endoplasmic reticulum, lysosomes, lipid droplets, ions, etc. Förster resonance energy transfer (FRET) analysis of living cells showed that cofilin and actin only interact in TNTs, and inhibition of cofilin can suppress oxidative stress-induced TNTs production. Doxorubicin (DOX) induced senescent tumor cells (STC) can form TNTs, and TNTs mediated material transfer between STC can promote tumor cell survival, while inhibition of cofilin can promote STC death. In summary, our data suggests that cofilin plays an important role in the formation of TNTs, and targeted inhibition of TNTs mediated intercellular communication and material exchange holds significant potential as a novel cancer treatment strategy.

隧道纳米管（TNTs）是细胞间开放的膜通道，其介导的肿瘤细胞间物质转移在肿瘤的耐药、转移和复发中起着重要作用。本研究旨在探讨肿瘤细胞间TNTs的组成及cofilin在TNTs形成中的作用。氧化应激诱导肿瘤细胞间形成tnt。tnt的成分包括微丝和细胞膜，其中一些含有微管，还有线粒体、内质网、溶酶体、脂滴、离子等。Förster活细胞的共振能量转移（FRET）分析表明，cofilin和actin仅在tnt中相互作用，抑制cofilin可以抑制氧化应激诱导的tnt的产生。多柔比星（DOX）诱导的衰老肿瘤细胞（STC）可形成tnt， tnt介导的STC间物质转移可促进肿瘤细胞存活，抑制cofilin可促进STC死亡。总之，我们的数据表明，cofilin在TNTs的形成中起着重要作用，靶向抑制TNTs介导的细胞间通讯和物质交换具有作为一种新的癌症治疗策略的巨大潜力。

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引用次数: 0

Cannabigerol – A potent regulator of insulin sensitivity in rat’s skeletal muscle via targeting the sphingolipid metabolism and PI3K/Akt/mTOR pathway? 大麻酚-通过靶向鞘脂代谢和PI3K/Akt/mTOR通路有效调节大鼠骨骼肌胰岛素敏感性？

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-06 DOI: 10.1016/j.biocel.2025.106819

Patrycja Bielawiec , Lara Swierkot , Karolina Konstantynowicz-Nowicka , Adrian Chabowski , Agnieszka Błachnio-Zabielska , Ewa Harasim-Symbor

Despite the great advances in medicine, there is a compelling need to develop alternative strategies to effectively treat obesity with the use of plant-origin therapeutics. Cannabigerol (CBG) appears to be a novel promising compound for managing this increasingly prevalent disease requiring multifaceted pharmacotherapy. Therefore, the herein study aimed to evaluate the potential therapeutic properties of 2-week CBG administration on the muscular metabolism of sphingolipids as well as insulin signal transduction pathway in a rat model of obesity and insulin resistance (IR) induced by high-fat, high-sucrose (HFHS) diet. The high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) were used to determine the sphingolipids content, while the multiplex assay kit was applied to measure the level of the phosphorylated form of proteins from the PI3K/Akt/mTOR pathway. The expression of various proteins engaged in the sphingolipid metabolism and insulin signaling was assessed using Western blotting. Our results showed that 2-week CBG treatment decreased the muscular content of most deleterious C16:0-Cer and C18:0-Cer ceramide species and reduced the intramuscular concentrations of sphinganine (SFA) and sphingosine (SFO), redirecting their metabolism toward phosphorylated derivatives, sphinganine-1-phosphate (SFA1P), and sphingosine-1-phosphate (S1P), respectively. Simultaneously, CBG counteracted S1P efflux in skeletal muscle, inhibiting the tissue-specific S1P/S1PR3 signaling. CBG also activated the PI3K/Akt/mTOR pathway, which increased the phosphorylation of protein kinase B (Akt) and its downstream targets in the myocytes of obese rats. These results suggest that CBG may play an essential homeostatic role in skeletal muscles and can protect from the development of obesity-associated metabolic derangements.

尽管医学取得了巨大的进步，但迫切需要开发替代策略，利用植物来源的疗法来有效治疗肥胖。大麻酚（CBG）似乎是一种新的有前途的化合物，用于管理这种日益普遍的疾病，需要多方面的药物治疗。因此，本研究旨在评估2周CBG对高脂高糖饮食诱导的肥胖和胰岛素抵抗（IR）大鼠肌肉鞘脂代谢和胰岛素信号转导通路的潜在治疗作用。采用高效液相色谱法（HPLC）和超高效液相色谱-串联质谱法（UHPLC/MS/MS）检测鞘脂含量，采用多重检测试剂盒检测PI3K/Akt/mTOR通路磷酸化蛋白的水平。Western blotting检测参与鞘脂代谢和胰岛素信号传导的各种蛋白的表达。我们的研究结果表明，2周的CBG处理降低了肌肉中最有害的C16:0-Cer和C18:0-Cer神经酰胺种类的含量，降低了肌内鞘氨酸（SFA）和鞘氨醇（SFO）的浓度，使它们的代谢分别转向磷酸化衍生物鞘氨氨酸-1-磷酸（SFA1P）和鞘氨醇-1-磷酸（S1P）。同时，CBG抵消骨骼肌中的S1P外排，抑制组织特异性S1P/S1PR3信号。CBG还激活了PI3K/Akt/mTOR通路，增加了肥胖大鼠肌细胞中蛋白激酶B （Akt）及其下游靶点的磷酸化。这些结果表明CBG可能在骨骼肌中发挥重要的体内平衡作用，并可以防止肥胖相关代谢紊乱的发生。

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引用次数: 0

Bifidobacterium apoptosis induction by measuring bax and caspases on SW948 human colon cancer cell line 双歧杆菌诱导SW948人结肠癌细胞凋亡的Bax和caspase测定

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-03 DOI: 10.1016/j.biocel.2025.106813

Maryam Soraya , Elham Moazamian , Seyedeh Azra Shamsdin , Mehdi Dehghani

Background

Nowadays, probiotic bacteria have been considered as a factor in the prevention and treatment of cancer, especially by induction of apoptosis. The aim of study, the isolation and identification of Bifidobacterium SPP, and to investigate the effects of bacterial cell extract and cell free supernatants (CFS) was on normal cell line and colon cancer cell line through measuring caspases.

Material and method

In this study, dairy products were collected and After isolation and identification of Bifidobacterium via PCR method, the cytotoxicity effects of cell free supernatants (CFS) (B.Bifidum S2 and B.Bifidum S3) and bacterial cell extract (B.Bifidum P6 and B.Bifidum P17) on colon cancer cell line (SW948) and normal cell line (HEK-293) were evaluated using MTT assay. The effect of isolated bacterial strains on apoptotic cells was determined by measuring caspases 1, 3, 9 and Bax by using ELISA kit.

Result

The results showed that the cytotoxicity effect of CFS was higher than bacterial cell extract. CFS showed the highest cytotoxicity effect (about 95 %) on colon cancer cell line. Quantitative analysis of Caspase-1, −3, 9, and Bax expression demonstrated that CFS may exert anticancer effects through induced apoptosis.

Conclusion

The results of the present research indicate that probably B.Bifidum S2 and B.Bifidum S3 isolates may be prevent colon cancer by inducing apoptosis.

背景：目前，益生菌已被认为是预防和治疗癌症的一个因素，特别是通过诱导细胞凋亡。目的：分离鉴定双歧杆菌SPP，并通过检测半胱天冬酶，探讨细菌细胞提取物和无细胞上清液（CFS）对正常细胞株和结肠癌细胞株的影响。材料与方法：本研究收集乳制品，采用PCR法分离鉴定双歧杆菌，采用MTT法评价无细胞上清（CFS）（b.b hibifidum S2和b.b bifidum S3）和细菌细胞提取物（b.b hibifum P6和b.b bifidum P17）对结肠癌细胞株SW948和正常细胞株HEK-293的细胞毒性作用。采用ELISA试剂盒检测caspase 1、3、9和Bax，观察分离菌株对凋亡细胞的影响。结果：CFS的细胞毒作用明显高于细菌细胞提取物。CFS对结肠癌细胞系的细胞毒作用最高（约95%）。Caspase-1、-3、9、Bax表达的定量分析表明，CFS可能通过诱导细胞凋亡发挥抗癌作用。结论：本研究结果提示双歧杆菌S2和双歧杆菌S3分离株可能通过诱导细胞凋亡来预防结肠癌。

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引用次数: 0

Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic resilience to cytotoxic stress 中剂量照射损害造血干细胞的长期功能和造血对细胞毒性应激的恢复能力

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-06-03 DOI: 10.1016/j.biocel.2025.106814

Qinyu Zhang , Anna Rydström , Isabel Hidalgo , Jörg Cammenga , Alexandra Rundberg Nilsson

Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system’s resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II^- HSCs – a subset characterized by high self-renewal potential and hypersensitivity to irradiation-induced ROS production. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by substantially reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.

照射和5-氟尿嘧啶（5-FU）是造血研究中广泛使用的工具，用于产生骨髓消融和评估血液恢复动力学。全面了解它们对造血系统的影响对于优化治疗策略、完善实验模型以调节血液毒性和解释研究结果至关重要。尽管其广泛应用，但辐射和5-FU的长期造血影响，特别是对造血干细胞（hsc）的影响仍未完全表征。因此，在本研究中，我们研究了2 Gy中剂量电离辐射（MDIR）和150 mg/kg 5-FU对小鼠造血干细胞和造血系统对随后细胞毒性应激的恢复能力的长期影响。我们的研究结果表明，MDIR，而不是5-FU，诱导HSC功能的持续损伤，并导致MHC II类- HSC的选择性消耗，MHC II类- HSC是一种具有高自我更新潜力和对辐射诱导的ROS产生超敏感的亚群。此外，MDIR显著损害了5-FU刺激后的造血恢复，在关键恢复阶段血小板和红细胞（RBC）计数显著减少。这些发现强调了MDIR和5-FU对造血干细胞和造血功能的独特而持久的影响，揭示了它们在作用机制和对造血系统的长期影响方面的关键差异。

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