Biochemistry and Biophysics Reports最新文献_第9页

Hibiscus sabdariffa calyx aqueous extract mitigates alcohol withdrawal-induced anxiety and oxidative stress in mice 芙蓉花萼水提物减轻小鼠酒精戒断诱导的焦虑和氧化应激

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.bbrep.2025.102423

Nadège Emégam Kouémou , Louis Aimé Sepi , Mireille Sylviane Nguepi Dongmo , Ndzweng Linda Tamanji , Franklin Savo Mbeboh , Stephanie Jacqueline Kameni Ndjapdounke , Paul Aimé Noubissi , Bernard Tiencheu , Elisabeth Ngo Bum

Background

Alcohol withdrawal syndrome (AWS) happens following a sudden interruption of chronic alcohol intake. AWS is a severe condition, often leading to anxiety and seizures. Current treatments against AWS do not target all the features of the disease. This study aimed to evaluate Hibiscus sabdariffa aqueous extract on AWS in mice.

Methods

Thirty-five male mice were grouped into seven sets of 5 animals. Each set (except the sham control) received alcohol (5 %) as drinking water and, in addition, alcohol at increasing concentrations (5 %–35 %, 0.4 g/kg to 2.8 g/kg) once every 24 h for 28 days. After alcohol weaning on day 29, anxiety was evaluated (days 29–31). Following behavioural recording, animals were euthanised. Brain and liver homogenates were used for biochemical evaluation of oxidative stress parameters. Alanine aminotransferase and Aspartate aminotransferase were assessed in the serum.

Results

Alcohol withdrawal led to a significant (P < 0.001) decrease in open arm activities in the elevated plus maze. Hibiscus sabdariffa administration reversed the ethanol effect and increased open arms stay and exploration. Hibiscus sabdariffa also significantly (P < 0.05) increased center exploration of the open field, which was reduced by alcohol withdrawal. A treatment with Hibiscus sabdariffa significantly (P < 0.01) reduced the increase of brain and liver oxidation induced by alcohol withdrawal. Serum Alanine aminotransferase level was also significantly (P < 0.001) decreased by Hibiscus sabdariffa extract.

Conclusion

This study's results justify the traditional utilisation of the drinks prepared from Hibiscus sabdariffa cayxes in treating patients suffering from AWS.

背景：酒精戒断综合征（AWS）发生在慢性酒精摄入突然中断后。AWS是一种严重的疾病，通常会导致焦虑和癫痫发作。目前针对AWS的治疗方法并没有针对该疾病的所有特征。本研究旨在评价芙蓉水提物对小鼠AWS的影响。方法35只雄性小鼠分为7组，每组5只。每组（假对照组除外）均以酒精（5 %）作为饮用水，此外，每24 h增加一次浓度的酒精（5 % -35 %，0.4 g/kg至2.8 g/kg），持续28天。第29天戒酒后，评估焦虑（第29 - 31天）。在行为记录之后，对动物实施安乐死。用脑和肝脏匀浆进行氧化应激参数的生化评价。测定血清丙氨酸转氨酶和天冬氨酸转氨酶。结果酒精戒断导致高架+迷宫中张开臂活动显著降低（P <； 0.001）。芙蓉提取物逆转了乙醇效应，增加了张开的手臂停留和探索。芙蓉也显著（P <； 0.05）增加了裸地的中心探索，酒精戒断降低了中心探索。木槿提取物显著（P <； 0.01）降低了酒精戒断引起的脑和肝脏氧化的增加。木槿提取物也显著降低了血清丙氨酸转氨酶水平（P <； 0.001）。结论本研究的结果证明了传统的利用芙蓉饮料治疗AWS患者是合理的。

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引用次数: 0

Accumulation of prosaposin and progranulin around the subfornical organ induces polydipsia in SAP-D-deficient mice 磷酸腺苷和颗粒前蛋白在皮质下器官周围的积累引起了sap -d缺乏小鼠的烦渴

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI: 10.1016/j.bbrep.2025.102388

Harumi Hisaki , Takao Susa , Noriyuki Okudaira , Miho Akimoto , Masayoshi Iizuka , Junko Matsuda , Shunya Uchida , Hiroko Okinaga , Tomoki Okazaki , Mimi Tamamori-Adachi

Prosaposin (PSAP), a precursor of saposins, is essential for lysosomal hydrolysis of sphingolipids. It binds with progranulin (PGRN) and transports from the Golgi to lysosomes, where it is processed into saposins. PSAP is also secreted and functions on various cells, including neurons. We found that PSAP is highly expressed in the subfornical organ (SFO), a thirst center, in SAP-D-deficient (SAP-D^−/−) mice, which develop primary polydipsia. As polyuria progresses, CD68-positive active microglia infiltrate the SFO and strongly express PSAP and PGRN. Lysosomal marker LAMP1 analysis in the SFO of mice with advanced polydipsia showed increased LAMP1 expression and decreased co-localization of PSAP and LAMP1 in microglia and neurons. This suggests that SAP-D-deficient PSAP struggles to reach lysosomes, causing intracellular accumulation. c-Fos-positive cell counts in the SFO remained significantly higher in SAP-D^−/− mice, reflecting altered drinking behavior. These findings imply that PSAP may drive polydipsia progression.

丙皂苷（PSAP）是皂苷的前体，是溶酶体水解鞘脂所必需的。它与颗粒前蛋白（PGRN）结合，从高尔基体转运到溶酶体，在那里加工成皂苷。PSAP也在包括神经元在内的多种细胞上分泌并起作用。我们发现PSAP在SAP-D缺乏（sap - / -）小鼠的皮层下器官（SFO）中高度表达，这是一个口渴中心，会发生原发性多饮。随着多尿的进展，cd68阳性的活性小胶质细胞浸润SFO并强烈表达PSAP和PGRN。晚期多饮小鼠SFO溶酶体标记物LAMP1分析显示，LAMP1表达增加，PSAP和LAMP1在小胶质细胞和神经元中的共定位减少。这表明缺乏sap -d的PSAP难以到达溶酶体，导致细胞内积聚。在SAP-D - / -小鼠中，SFO中c- fos阳性细胞计数仍显着升高，反映了饮酒行为的改变。这些发现暗示PSAP可能推动烦渴的进展。

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引用次数: 0

Neuroprotective potential of polyherbal formulation: Evidence from preliminary in-vitro and in-vivo studies 多草药配方的神经保护潜力：来自体外和体内初步研究的证据

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI: 10.1016/j.bbrep.2025.102381

Kundlik Rathod, Aswar Urmila

The objective of the study is to develop and evaluate a polyherbal formulation (PHF) for Parkinson's disease (PD). The present research provides preliminary studies which includes exhaustive literature survey leading to the selection of seven medicinal plants. Hydroalcoholic extracts of these plants were subsequently evaluated for their efficacy using haloperidol catalepsy and antioxidant assay. Based on results, four potent extracts, Asparagus racemosus, Convolvulus prostratus, Bacopa monnieri, and Nigella sativa, were chosen for further research. A PHF containing the above extracts was prepared and assessed for physicochemical properties, microbial load, and bioactive constituents. HPTLC analysis confirmed the presence of quercetin, kaempferol, rutin, and β-sitosterol. Molecular docking was performed for the promising actives present in the above extracts, such as kaempferol, quercetin, rutin, and β-sitosterol, highlighting their potential interactions with the PD-related targets. Antioxidant activity was evaluated using DPPH, ABTS, and FRAP assays, confirming potent free radical scavenging properties. Anti-inflammatory effects were demonstrated via heat-induced hemolysis, albumin denaturation, and proteinase inhibition assays. Additionally, the MAO-B enzyme inhibition assay indicated significant antiparkinsonian potential. PHF, combined with antioxidant, anti-inflammatory, and MAO-B inhibitory activities, supports its therapeutic application in neuronal protection. Acute oral toxicity was assessed as per OECD 425 guidelines, confirming its safety.

该研究的目的是开发和评估一种治疗帕金森病（PD）的多草药配方（PHF）。本研究提供了初步研究，包括详尽的文献调查，从而选择了七种药用植物。这些植物的水酒精提取物随后用氟哌啶醇麻醉和抗氧化试验评估其功效。在此基础上，选择总状芦笋、旋花、假马齿苋和黑草四种有效提取物进行进一步研究。制备了含有上述提取物的PHF，并对其理化性质、微生物负荷和生物活性成分进行了评估。hplc分析证实含有槲皮素、山奈酚、芦丁和β-谷甾醇。对上述提取物中存在的有希望的活性物质，如山奈酚、槲皮素、芦丁和β-谷甾醇进行了分子对接，突出了它们与pd相关靶点的潜在相互作用。使用DPPH， ABTS和FRAP测定评估抗氧化活性，证实了有效的自由基清除特性。通过热诱导溶血、白蛋白变性和蛋白酶抑制实验证明了抗炎作用。此外，MAO-B酶抑制试验显示了显著的抗帕金森病潜力。PHF具有抗氧化、抗炎和MAO-B抑制活性，支持其在神经元保护方面的治疗应用。急性口服毒性根据OECD 425指南进行评估，确认其安全性。

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引用次数: 0

Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications 肝细胞癌（HCC）转移和侵袭的信号通路：分子机制和治疗意义

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-09 DOI: 10.1016/j.bbrep.2025.102403

Jayanta Das , Bhupen Barman , Phulen Sarma , Bipul Kumar Das , Rajiv Chetia , Partha Pratim Kalita

HCC is one of the deadliest malignancies with a rising global occurrence and poor prognosis. Metastasis and invasion are essential processes in the HCC progression, and have a profound bearing on clinical outcome. This review explores the key signalling pathways involved in HCC metastasis and invasion, focusing on their molecular mechanisms, crosstalk, and therapeutic implications. Alongside the discussion of the Wnt/β-catenin, TGF-β, PI3K/AKT/mTOR, MAPK/ERK, HGF/c-MET, Notch and Hippo-YAP/TAZ pathways, are known to contribute to promoting aggressive HCC behaviour. Stromal interactions, extracellular matrix remodelling, hypoxia and angiogenesis as well as the tumour microenvironment are also highlighted. These pathways are subject to current therapeutic treatments in the form of tyrosine kinase inhibitors and monoclonal antibodies, and research prospective of the Wnt/β-catenin blocker, TGF-β inhibitors, etc. The variations in tumours and resistance patterns to treatment and their existing problems in treating HCC are addressed. The review evaluates new therapeutic targets offering a foundation for further research and clinical advancements in this challenging field.

HCC是最致命的恶性肿瘤之一，全球发病率不断上升，预后不良。转移和侵袭是HCC发展的重要过程，对临床预后有着深远的影响。本文综述了参与HCC转移和侵袭的关键信号通路，重点讨论了它们的分子机制、串扰和治疗意义。除了讨论Wnt/β-catenin外，TGF-β、PI3K/AKT/mTOR、MAPK/ERK、HGF/c-MET、Notch和Hippo-YAP/TAZ通路也有助于促进HCC的侵袭性行为。间质相互作用，细胞外基质重塑，缺氧和血管生成以及肿瘤微环境也被强调。这些途径受到当前以酪氨酸激酶抑制剂和单克隆抗体形式的治疗，以及Wnt/β-catenin阻断剂、TGF-β抑制剂等的研究前景。讨论了肝癌治疗中肿瘤和耐药模式的变化及其存在的问题。该综述评估了新的治疗靶点，为这一具有挑战性的领域的进一步研究和临床进展提供了基础。

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引用次数: 0

How do vibration stimulation frequencies affect the nonlinear dynamics and mechanical characterization of breast cancer cells? 振动刺激频率如何影响乳腺癌细胞的非线性动力学和力学特性？

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-15 DOI: 10.1016/j.bbrep.2025.102414

Ashkan Heydarian , Dornaz Milani , Hamidreza Mortazavy Beni , Mehrafarin Babaee , Hamid Reza Goudarzi

Introduction

Understanding the mechanical properties of cells is crucial for gaining insights into their physiological and pathological states. This study focuses on the mechanical behavior of human mammary epithelial cells (MCF-10) and human breast cancer cells (MCF-7), emphasizing mechanical frequencies, finite element modeling (FEM), and nonlinear dynamics of the cells.

Methods

Cells were cultured and subjected to mechanical testing using Atomic Force Microscopy (AFM) and Magnetic Tweezer Cytometry (MTC). The elastic and viscoelastic properties were analyzed, and FEMs were developed to simulate cell behavior under various mechanical stimuli. The nonlinear dynamic behavior was examined using the Duffing model, and chaos was assessed using the Largest Lyapunov exponent (LLE).

Results

MCF-10 cells exhibited higher stiffness than MCF-7 cells. The mechanical frequencies of both cell types were determined, and significant differences were observed at higher frequencies. FEM simulations provided detailed insights into the stress distribution and deformation patterns within cells. The nonlinear analysis revealed chaotic behavior at specific frequencies, particularly in the range of 22–36 kHz.

Conclusion

Identifying the mechanical frequencies and responses of cancer cells, including their nonlinear and chaotic behaviors, can inform the development of noninvasive therapeutic strategies. Further research is required to refine these models and explore the potential of mechanical forces in cancer treatment.

了解细胞的力学特性对于深入了解其生理和病理状态至关重要。本研究的重点是人乳腺上皮细胞（MCF-10）和人乳腺癌细胞（MCF-7）的力学行为，强调细胞的力学频率、有限元建模（FEM）和非线性动力学。方法采用原子力显微镜（AFM）和磁钳细胞术（MTC）对细胞进行力学检测。分析了材料的弹性和粘弹性特性，并开发了有限元模型来模拟各种机械刺激下的细胞行为。采用Duffing模型分析了系统的非线性动力学行为，采用最大李雅普诺夫指数（LLE）评价了系统的混沌性。结果smcf -10 细胞比MCF-7 细胞具有更高的刚度。测定了两种细胞类型的机械频率，在较高频率处观察到显著差异。有限元模拟提供了细胞内应力分布和变形模式的详细见解。非线性分析揭示了在特定频率下的混沌行为，特别是在22-36 kHz范围内。结论识别癌细胞的力学频率和反应，包括它们的非线性和混沌行为，可以为无创治疗策略的制定提供信息。需要进一步的研究来完善这些模型，并探索机械力在癌症治疗中的潜力。

{"title":"How do vibration stimulation frequencies affect the nonlinear dynamics and mechanical characterization of breast cancer cells?","authors":"Ashkan Heydarian , Dornaz Milani , Hamidreza Mortazavy Beni , Mehrafarin Babaee , Hamid Reza Goudarzi","doi":"10.1016/j.bbrep.2025.102414","DOIUrl":"10.1016/j.bbrep.2025.102414","url":null,"abstract":"<div><h3>Introduction</h3><div>Understanding the mechanical properties of cells is crucial for gaining insights into their physiological and pathological states. This study focuses on the mechanical behavior of human mammary epithelial cells (MCF-10) and human breast cancer cells (MCF-7), emphasizing mechanical frequencies, finite element modeling (FEM), and nonlinear dynamics of the cells.</div></div><div><h3>Methods</h3><div>Cells were cultured and subjected to mechanical testing using Atomic Force Microscopy (AFM) and Magnetic Tweezer Cytometry (MTC). The elastic and viscoelastic properties were analyzed, and FEMs were developed to simulate cell behavior under various mechanical stimuli. The nonlinear dynamic behavior was examined using the Duffing model, and chaos was assessed using the Largest Lyapunov exponent (LLE).</div></div><div><h3>Results</h3><div>MCF-10 cells exhibited higher stiffness than MCF-7 cells. The mechanical frequencies of both cell types were determined, and significant differences were observed at higher frequencies. FEM simulations provided detailed insights into the stress distribution and deformation patterns within cells. The nonlinear analysis revealed chaotic behavior at specific frequencies, particularly in the range of 22–36 kHz.</div></div><div><h3>Conclusion</h3><div>Identifying the mechanical frequencies and responses of cancer cells, including their nonlinear and chaotic behaviors, can inform the development of noninvasive therapeutic strategies. Further research is required to refine these models and explore the potential of mechanical forces in cancer treatment<strong>.</strong></div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102414"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the inflammatory response to exposure of ultrafine TiO2 particulate matter to HUVECs 研究超细TiO2颗粒物质暴露于HUVECs的炎症反应

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.bbrep.2025.102426

Laura A.E. Brunmaier, Travis W. Walker

Epidemiological studies have indicated that strong causal evidence exists to link the inhalation of particulate matter to the exacerbation of pathology in the cardiovascular system, ranging from myocardial infarction and atherosclerosis to direct cytotoxicity and inflammation. Ultrafine particles are ubiquitous in ambient air, in industrial sites, and in air pollution. When particles are inhaled, deposition can occur in the lungs, and the mechanisms of pathology have been well-studied. However, ultrafine particulate matter can translocate from the lungs into the bloodstream to circulate throughout the body (Choi et al. 2010).Contradictory evidence exists of inflammation and cytotoxicity that is caused from nanoparticle exposure to the endothelium.

When endothelial cells (ECs) are adversely stimulated, they have been shown to secrete cytokines that mediate an inflammatory response. Currently, studies that quantitatively evaluated the secretion of pro-inflammatory cytokines from ECs upon nanoparticle exposure are not accounting for the aggregation that can occur between particles over time and, therefore, are likely exposing cells to a wider range of aggregated sizes. This study evaluates the inflammatory response from ECs after particle exposure, with acute attention devoted to controlling particle aggregation. Specifically, we introduce a protocol that exposes ECs to the particles in a transwell system, where we take advantage of the effects of gravitational settling to expose the ECs only to the smallest fraction of the particles that are in suspension. After 72 h in the transwell assay, we found that the inflammatory response between varying concentrations of particles mirrored the inflammatory response of the positive control of lipopolysaccharide (LPS). These results indicate that the inflammatory response may have a stronger relationship to the particle size than to the concentration of the particles in mass per volume.

流行病学研究表明，有强有力的因果证据表明，颗粒物质的吸入与心血管系统的病理恶化有关，从心肌梗死和动脉粥样硬化到直接的细胞毒性和炎症。超细颗粒在环境空气、工业场所和空气污染中无处不在。当颗粒被吸入，沉积可发生在肺部，病理机制已被充分研究。然而，超细颗粒物可以从肺部转移到血液中，在全身循环（Choi et al. 2010）。存在相互矛盾的证据表明，炎症和细胞毒性是由纳米颗粒暴露于内皮细胞引起的。当内皮细胞（ECs）受到不良刺激时，它们已被证明会分泌介导炎症反应的细胞因子。目前，定量评估纳米颗粒暴露后内皮细胞促炎细胞因子分泌的研究并没有考虑颗粒之间随着时间的推移可能发生的聚集，因此，可能会使细胞暴露于更大范围的聚集大小。本研究评估颗粒暴露后ECs的炎症反应，重点关注控制颗粒聚集。具体来说，我们引入了一种将ec暴露于transwell系统中的粒子的协议，在该协议中，我们利用重力沉降的影响，使ec仅暴露于悬浮粒子的最小部分。在transwell实验72小时后，我们发现不同浓度颗粒之间的炎症反应反映了脂多糖（LPS）阳性对照的炎症反应。这些结果表明，炎症反应可能与颗粒大小的关系比与每体积颗粒的质量浓度的关系更强。

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引用次数: 0

A simple and rapid method for generating antibodies against bovine alphaherpesvirus 1 viral proteins through immunization with virus-infected murine cells 用病毒感染的小鼠细胞免疫产生牛甲疱疹病毒1型病毒蛋白抗体的一种简单快速的方法

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI: 10.1016/j.bbrep.2026.102450

Jiayu Lin , Xiaozhen Ma , Naifan Zhang , Yue Pang , Filomena Fiorito , Xiuyan Ding , Liqian Zhu

Bovine alphaherpesvirus 1 (BoAHV-1) infects cattle and typically results in significant economic losses for the cattle industry worldwide. Currently, antibodies targeting only a limited number of viral proteins are commercially available. It has been reported that BoAHV-1 is capable of infecting numerous tumor cell lines. Based on the rationale of immune tolerance, we hypothesized that virus-infected murine cells could be directly used to immunize mice, thereby generating antibodies against viral proteins. In this study, we found that BoAHV-1 can infect murine cell lines including LA795 and MC38, as determined using both Western blot and immunofluorescence analyses. Immunizing mice with virus-infected cells, either through subcutaneous or intraperitoneal injection, stimulates the production of high levels of antibodies that specifically recognize the viral proteins synthesized in bovine kidney (MDBK) cells, as characterized by both Western blot and/or immunofluorescence. Furthermore, our findings suggest that intraperitoneal immunization could more effectively elicit antibodies against a wider array of viral proteins. As a homemade antibody generation method, this approach bypasses the complex and time-consuming steps of producing and purifying recombinant proteins as antigen, which are typically performed in conventional methods for antibody generation. Thus, we present a simple, rapid, and cost-effective method for generating virus-specific antibodies.

牛甲疱疹病毒1型（BoAHV-1）感染牛，通常给全世界的养牛业造成重大经济损失。目前，仅针对有限数量的病毒蛋白的抗体在商业上可用。据报道，BoAHV-1能够感染多种肿瘤细胞系。基于免疫耐受的原理，我们假设病毒感染的小鼠细胞可以直接用于免疫小鼠，从而产生针对病毒蛋白的抗体。在这项研究中，我们发现BoAHV-1可以感染小鼠细胞系，包括LA795和MC38，通过Western blot和免疫荧光分析确定。通过皮下或腹腔注射，用病毒感染的细胞免疫小鼠，刺激产生高水平的抗体，特异性识别牛肾（MDBK）细胞中合成的病毒蛋白，其特征是Western blot和/或免疫荧光。此外，我们的研究结果表明，腹腔免疫可以更有效地引发针对更广泛病毒蛋白的抗体。作为一种自制抗体生成方法，该方法绕过了生产和纯化重组蛋白作为抗原的复杂而耗时的步骤，而传统的抗体生成方法通常需要进行这些步骤。因此，我们提出了一种简单、快速、经济的方法来产生病毒特异性抗体。

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引用次数: 0

Anti-cancer effect of palmitic acid against the endometrial cancer progression via inducing ferroptosis 棕榈酸通过诱导铁下垂对子宫内膜癌进展的抗癌作用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI: 10.1016/j.bbrep.2026.102499

Shuting Lan , Xiaomei Sun , Qiyuan Bo , Suriguga Wang , Yifan Qin , Jianying Mao

Background

The critical role of metabolic reprogramming as a potential therapeutic target in the management of endometrial cancer (EC) progression requires further investigation. This study investigated the anti-cancer effect of palmitic acid (PA) on EC progression using cellular and xenograft models, combined with integrated transcriptomic and metabolomic analyses to elucidate the molecular pathways through which PA induces ferroptosis and inhibits tumor growth.

Methods

The anti-cancer effects of PA were assessed through comprehensive in vitro assays, including cell viability, proliferation, migration, invasion, adhesion, clonogenicity, cell-cycle distribution, apoptosis, and epithelial-mesenchymal transition (EMT). In vivo, the therapeutic efficacy of PA was evaluated using a xenograft mouse model. Transcriptomic and metabolomic profiling identified differentially expressed genes (DEGs) and metabolites, with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses further exploring PA's mechanistic impact.

Results

PA significantly reduced the viability, migration, invasion, clonogenic potential, and EMT of EC cells, while inducing cell-cycle arrest and apoptosis. In xenograft models, PA effectively suppressed tumor growth. Mechanistically, transcriptomic and metabolomic analyses, together with changes in ferroptosis-related markers, indicated that PA exerts its anti-cancer effects at least in part through ferroptosis activation. This conclusion was further supported by multiple ferroptosis hallmarks and ferrostatin-1 rescue, which substantially attenuated PA-induced phenotypic and biochemical alterations.

Conclusion

PA suppressed EC progression by inducing ferroptosis, providing novel mechanistic insights into PA's anti-cancer properties and underscoring its potential as a therapeutic candidate for EC treatment.

代谢重编程作为子宫内膜癌（EC）进展管理的潜在治疗靶点的关键作用需要进一步研究。本研究利用细胞和异种移植模型，结合整合转录组学和代谢组学分析，研究棕榈酸（PA）对EC进展的抗癌作用，以阐明PA诱导铁下垂和抑制肿瘤生长的分子途径。方法通过细胞活力、增殖、迁移、侵袭、粘附、克隆性、细胞周期分布、细胞凋亡、上皮-间质转化（EMT）等综合体外实验，评价PA的抗癌作用。在体内，采用异种移植小鼠模型评估PA的治疗效果。转录组学和代谢组学分析鉴定了差异表达基因（DEGs）和代谢物，通过基因本体（GO）和京都基因与基因组百科全书（KEGG）途径富集分析进一步探索了PA的机制影响。结果spa显著降低EC细胞的活力、迁移、侵袭、克隆潜能和EMT，诱导细胞周期阻滞和凋亡。在异种移植物模型中，PA有效抑制肿瘤生长。从机制上讲，转录组学和代谢组学分析以及与铁下垂相关的标志物的变化表明，PA至少部分通过铁下垂激活发挥其抗癌作用。这一结论进一步得到了多个铁下垂标志和铁抑素-1拯救的支持，铁抑素-1大大减轻了pa诱导的表型和生化改变。结论PA通过诱导铁下垂抑制EC进展，为PA抗癌特性提供了新的机制见解，并强调了其作为EC治疗候选药物的潜力。

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引用次数: 0

Influence of fluid shear stress on human limbal epithelial cells 流体剪切应力对人角膜缘上皮细胞的影响

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-17 DOI: 10.1016/j.bbrep.2026.102453

Sophia Masterton , Mark Ahearne

Background/aims

Limbal epithelial cells (LECs) have a crucial role in the maintenance of the corneal surface by migrating from the limbus to the cornea and replacing corneal epithelial cells. These cells are subjected to shear stress via blinking and tear film movement but the influence this stress has on the cells is poorly understood. The aim of this study was to examine how fluidic shear stress can affect the behaviour of LECs from different donors.

Methods

A commercial fluid flow system (ibidi) was used to apply fluid shear at two different flow rates, with no flow being used as a control. Cells from three different donors were examined for phenotype, stratification, TRPV4 activation, cell adhesion and barrier function.

Results

Both low and high shear stresses resulted in changes to the cell phenotype and these changes were highly donor dependent. Expression of TRPV4, a mechanosensitive ion-channel, was up-regulated for all donors exposed to shear stress. Stratification of cells only occurred with cells exposed to shear stress.

Conclusion

This study show the importance of shear stress on modulating the behaviour of LECs and how donor to donor variations and the heterogeneity of cell populations need to be considered when conducting cell based studies.

背景/目的角膜缘上皮细胞（lec）通过从角膜缘向角膜迁移并替代角膜上皮细胞，在维持角膜表面中起着至关重要的作用。这些细胞通过眨眼和撕裂膜运动受到剪切应力，但这种应力对细胞的影响尚不清楚。本研究的目的是研究流体剪切应力如何影响来自不同供体的LECs的行为。方法采用商业流体流动系统（ibidi）在两种不同流速下施加流体剪切，不使用流量作为对照。对来自三种不同供体的细胞进行表型、分层、TRPV4活化、细胞粘附和屏障功能检测。结果低剪应力和高剪应力均可引起细胞表型的变化，且这些变化高度依赖于供体。TRPV4（一种机械敏感离子通道）的表达在所有暴露于剪切应力的供体中均上调。细胞分层只发生在细胞受到剪切应力时。本研究显示了剪切应力对调节LECs行为的重要性，以及在进行基于细胞的研究时，如何考虑供体之间的差异和细胞群体的异质性。

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引用次数: 0

Identification of PI3K/AKT/mTOR-related genes as diagnostic biomarkers for cutaneous squamous cell carcinoma PI3K/AKT/ mtor相关基因在皮肤鳞状细胞癌诊断中的应用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI: 10.1016/j.bbrep.2025.102355

Bingyan Yang, Hongyang Zhang, Lingdi Dong, Jianjun Wang, Nan Yu

Background

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer. Considering the substantial improvement in prognosis when detected at an early stage, identifying biomarkers for an early diagnosis of cSCC is crucial. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in cSCC progression; This study aimed to identify PI3K/AKT/mTOR-related genes that may serve as diagnostic indicators for cSCC, thereby providing a diagnostic framework for this disease.

Methods/results

A total of 33 PI3K/AKT/mTOR-related differentially expressed genes (DEGs) in cSCC were acquired by intersecting the DEGs from the Gene Expression Omnibus database between normal and cSCC groups and genes reported to be associated with the PI3K/AKT/mTOR pathway in the literature. LASSO regression identified 11 hub genes (AKT1, AKT3, EIF4EBP1, GFRA1, GRSF1, HIF1A, IGF1, IL11, IL24, KRT75, and MMP3), which were used to construct the diagnostic model. Receiver operating curve analysis revealed that these hub genes displayed strong diagnostic capacity. Quantitative polymerase chain reaction validation confirmed significant differences in mRNA expression of HIF1A, MMP3, IL11, GRSF1, and EIF4EBP1 between cSCC and normal cell lines.

Conclusion

These five PI3K/AKT/mTOR-related genes have the potential to serve as clinical biomarkers for the diagnosis of cSCC and as candidate therapeutic targets. This study offers valuable insights for further research to elucidate the specific pathological mechanisms and establish innovative treatment approaches for cSCC.

皮肤鳞状细胞癌（cSCC）是一种常见的皮肤癌。考虑到早期发现可显著改善预后，确定cSCC早期诊断的生物标志物至关重要。磷酸肌肽3-激酶(PI3K)/蛋白激酶B (AKT)/哺乳动物雷帕霉素靶蛋白（mTOR）通路在cSCC进展中起关键作用；本研究旨在鉴定可作为cSCC诊断指标的PI3K/AKT/ mtor相关基因，从而为cSCC提供诊断框架。方法/结果将基因表达综合数据库中正常组和cSCC组之间的差异表达基因（deg）和文献中报道的与PI3K/AKT/mTOR通路相关的基因相交，获得cSCC中33个PI3K/AKT/mTOR相关的差异表达基因（deg）。LASSO回归鉴定出11个中心基因（AKT1、AKT3、EIF4EBP1、GFRA1、GRSF1、HIF1A、IGF1、IL11、IL24、KRT75和MMP3），用于构建诊断模型。接受者工作曲线分析显示这些枢纽基因具有较强的诊断能力。定量聚合酶链反应验证证实，在cSCC和正常细胞系中，HIF1A、MMP3、IL11、GRSF1和EIF4EBP1 mRNA的表达存在显著差异。结论这5个PI3K/AKT/ mtor相关基因有潜力作为cSCC的临床生物标志物和候选治疗靶点。本研究为进一步阐明cSCC的具体病理机制和建立创新的治疗方法提供了有价值的见解。

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