Nifuroxazide

硝呋嗪
  • 文章类型: Journal Article
    背景:研究人员已经研究了用于合成碳点的不同技术。这些技术包括电弧放电,激光烧蚀,氧化,水/溶剂热,和化学气相沉积。然而,这些技术受到一些限制,如气体带电粒子的利用,大电流,高温,强效氧化剂,非环保碳源,并产生不均匀的颗粒大小。因此,人们非常需要采用一种新技术,该技术结合了生物基碳采购和合成技术的环保方面。
    结果:紫花苜蓿(苜蓿)衍生的N,已经通过微波辐射成功合成了S-CD。N,S-CD表现出强荧光(λex/em为320/420nm),荧光量子产率为2.2%,水溶性高。产生的N,S-CD用TEM表征,EDX,Zeta电位分析,IR,UV-可见光,和荧光光谱。产生的N的平均直径,S-CD为4.01±1.2nm,Zeta电位为-24.5±6.63mv。所生产的纳米传感器的稳定性也在宽pH范围内得到证实,长时间,并且存在不同的离子。合成的N,S-CD被用来量化抗菌药物,Nifuroxazide(NFZ),通过内部滤波效应机制实现荧光猝灭。该方法与NFZ浓度在1.0至30.0μM范围内呈线性关系。LOD和LOQ分别为0.16和0.49μM,分别。该方法用于量化模拟胃液(SGJ)中的NFZ,回收率为99.59±1.4,除了药物剂型外,AntinalCapsules®的回收率为98.75±0.61,Antinalsuspension®的回收率为100.63±1.54。方法验证按照ICH概述的标准进行。
    建议的方法主要集中在首次使用苜蓿,一种生态上可持续的多普勒CD来源,和通过微波辐射的经济有效的合成技术,其特点是能耗低,最小化反应时间,以及控制生产的CD大小的能力。这与全球对实施绿色分析化学原理的日益认可是一致的。
    BACKGROUND: Researchers have investigated different techniques for synthesis of carbon dots. These techniques include Arc discharge, laser ablation, oxidation, water/solvothermal, and chemical vapor deposition. However, these techniques suffer from some limitations like the utilization of gaseous charged particles, high current, high temperature, potent oxidizing agents, non-environmentally friendly carbon sources, and the generation of uneven particle size. Therefore, there was a significant demand for the adoption of a new technology that combines the environmentally friendly aspects of both bio-based carbon sourcing and synthesis technique.
    RESULTS: Medicago sativa L (alfalfa)-derived N, S-CDs have been successfully synthesized via microwave irradiation. The N,S-CDs exhibit strong fluorescence (λex/em of 320/420 nm) with fluorescence quantum yield of 2.2 % and high-water solubility. The produced N,S-CDs were characterized using TEM, EDX, Zeta potential analysis, IR, UV-Visible, and fluorescence spectroscopy. The average diameter of the produced N, S-CDs was 4.01 ± 1.2 nm, and the Zeta potential was -24.5 ± 6.63 mv. The stability of the produced nano sensors was also confirmed over wide pH range, long time, and in presence of different ions. The synthesized N, S-CDs were employed to quantify the antibacterial drug, nifuroxazide (NFZ), by fluorescence quenching via inner filter effect mechanism. The method was linear with NFZ concentration ranging from 1.0 to 30.0 μM. LOD and LOQ were 0.16 and 0.49 μM, respectively. The method was applied to quantify NFZ in simulated gastric juice (SGJ) with % recovery 99.59 ± 1.4 in addition to pharmaceutical dosage forms with % recovery 98.75 ± 0.61 for Antinal Capsules® and 100.63 ± 1.54 for Antinal suspension®. The Method validation was performed in compliance with the criteria outlined by ICH.
    UNASSIGNED: The suggested approach primarily centers on the first-time use of alfalfa, an ecologically sustainable source of dopped-CDs, and a cost-effective synthesis technique via microwave irradiation, which is characterized by low energy consumption, minimized reaction time, and the ability to control the size of the produced CDs. This is in line with the growing global recognition of the implementation of green analytical chemistry principles.
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  • 文章类型: Journal Article
    癌细胞异质性和治疗抗性主要来自代谢和转录适应。但是人们对它们之间的联系知之甚少。这里,我们证明,在黑色素瘤中,癌症干细胞标记醛脱氢酶1A3(ALDH1A3)与细胞核中的乙酰辅酶A(CoA)合成酶2(ACSS2)形成酶促伙伴关系,以将高葡萄糖代谢通量与神经c(NC)谱系和葡萄糖代谢基因的乙酰组蛋白H3修饰偶联。重要的是,我们表明乙醛是乙酰组蛋白H3修饰的代谢物来源,为这种高挥发性和毒性的代谢物提供生理功能。在斑马鱼黑色素瘤残留病模型中,BRAF抑制剂治疗后出现ALDH1高亚群,用ALDH1自杀抑制剂靶向这些药物,硝呋嗪,延迟或防止BRAF抑制剂耐药复发。我们的工作表明,ALDH1A3-ACSS2偶联直接协调核乙醛-乙酰-CoA代谢与特定的基于染色质的基因调控,并代表了黑色素瘤的潜在治疗脆弱性。
    Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.
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  • 文章类型: Journal Article
    泛素特异性蛋白酶(USP),一种催化蛋白质去泛素化的酶,参与与代谢紊乱和癌症增殖相关的生物过程。我们专注于构建预测模型,以揭示具有USP21抑制属性的化合物。六个模型,额外的树木分类器,随机森林分类器,LightGBM分类器,XGBoost分类器,Bagging分类器,并从经验数据中选择了卷积神经网络进行筛选过程。这些模型指导我们从FDA批准的药物库中选择26种化合物用于进一步评估。值得注意的是,硝呋嗪是最有效的抑制剂,半最大抑制浓度为14.9±1.63μM。使用分子建模确认蛋白质-配体复合物的稳定性。此外,Nifuroxazide处理HepG2细胞不仅抑制USP21及其建立的底物ACLY,而且升高p-AMPKα,USP21的下游功能靶标。有趣的是,我们揭示了以前未知的尼呋草嗪增加miR-4458水平的能力,miR-4458被鉴定为下调USP21.这一发现通过操纵HepG2细胞中的miR-4458水平得到证实,导致USP21蛋白水平的相应变化与其预测的与ACLY的相互作用一致。最后,我们证实了在小鼠肝脏中抑制USP21的体内功效,观察ACLY和p-AMPKα水平的同时变化。总的来说,我们的研究表明,硝呋嗪是一种有前景的USP21抑制剂,对解决代谢紊乱和癌症增殖具有潜在意义.这项多维研究揭示了涉及USP21及其下游效应的复杂调节机制,为进一步探索和治疗发展铺平了道路。
    Ubiquitin-specific protease (USP), an enzyme catalyzing protein deubiquitination, is involved in biological processes related to metabolic disorders and cancer proliferation. We focused on constructing predictive models tailored to unveil compounds boasting USP21 inhibitory attributes. Six models, Extra Trees Classifier, Random Forest Classifier, LightGBM Classifier, XGBoost Classifier, Bagging Classifier, and a convolutional neural network harnessed from empirical data were selected for the screening process. These models guided our selection of 26 compounds from the FDA-approved drug library for further evaluation. Notably, nifuroxazide emerged as the most potent inhibitor, with a half-maximal inhibitory concentration of 14.9 ± 1.63 μM. The stability of protein-ligand complexes was confirmed using molecular modeling. Furthermore, nifuroxazide treatment of HepG2 cells not only inhibited USP21 and its established substrate ACLY but also elevated p-AMPKα, a downstream functional target of USP21. Intriguingly, we unveiled the previously unknown capacity of nifuroxazide to increase the levels of miR-4458, which was identified as downregulating USP21. This discovery was substantiated by manipulating miR-4458 levels in HepG2 cells, resulting in corresponding changes in USP21 protein levels in line with its predicted interaction with ACLY. Lastly, we confirmed the in vivo efficacy of nifuroxazide in inhibiting USP21 in mice livers, observing concurrent alterations in ACLY and p-AMPKα levels. Collectively, our study establishes nifuroxazide as a promising USP21 inhibitor with potential implications for addressing metabolic disorders and cancer proliferation. This multidimensional investigation sheds light on the intricate regulatory mechanisms involving USP21 and its downstream effects, paving the way for further exploration and therapeutic development.
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  • 文章类型: Journal Article
    甲氨蝶呤(MTX)长期以来在几种肿瘤和自身免疫性疾病中表现出治疗功效。然而,MTX相关的肠毒性限制了治疗的继续。Nifuroxazide(NIF)是一种口服抗生素,被批准用于胃肠道感染,是一种有效的止泻药,具有很高的安全性。本研究旨在探索NIF在减轻与MTX化疗相关的肠道毒性方面的潜在功效,并阐明拟议的分子机制。给大鼠施用NIF(50mg/kg;p.o.)10天。第五天,给予单次腹膜内注射MTX(20mg/kg)以诱导肠中毒。实验结束时,十二指肠组织样本进行生化分离,西方印迹,免疫组织化学(IHC),通过H&E进行组织病理学分析,PSA,和阿尔西亚的蓝色污渍。NIF通过增强PPAR-γ的氧化还原敏感信号表达,对MTX肠中毒具有抗氧化保护作用,IHC估计的SIRT1和Nrf2。此外,NIF下调促炎细胞因子(TNF-α,IL-1β,IL-6),NF-κB蛋白表达,和JAK1/STAT3蛋白的磷酸化,导致肠道炎症的缓解。InAccording,组织学研究表明,NIF改善了肠道病理变化,保存了杯状细胞,减少了炎症细胞的浸润.因此,NIF可能是MTX辅助治疗的有希望的候选药物,以减轻相关的肠道损伤并增加其耐受性。
    Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for gastrointestinal infections as an effective antidiarrheal agent with a high safety profile. The current study was designed to explore the potential efficacy of NIF in alleviating intestinal toxicity associated with MTX chemotherapy with the elucidation of the proposed molecular mechanisms. Rats were administered NIF (50 mg/kg; p.o.) for ten days. On day five, a single i.p. injection of MTX (20 mg/kg) was given to induce intestinal intoxication. At the end of the experiment, duodenal tissue samples were isolated for biochemical, Western blotting, immunohistochemical (IHC), and histopathological analysis via H&E, PSA, and Alcian blue stains. NIF showed antioxidant enteroprotective effects against MTX intestinal intoxication through enhanced expression of the redox-sensitive signals of PPAR-γ, SIRT1, and Nrf2 estimated by IHC. Moreover, NIF down-regulated the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), NF-κB protein expression, and the phosphorylation of JAK1/STAT3 proteins, leading to mitigation of intestinal inflammation. In accordance, the histological investigation revealed that NIF ameliorated the intestinal pathological changes, preserved the goblet cells, and reduced the inflammatory cells infiltration. Therefore, NIF could be a promising candidate for adjunctive therapy with MTX to mitigate the associated intestinal injury and increase its tolerability.
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  • 文章类型: Journal Article
    吲哚美辛(INDO)是一种NSAID,具有显着的功效并广泛用于减轻疼痛。然而,肾功能损害是与INDO使用相关的不良反应.硝呋嗪(NFX),口服硝基呋喃抗生素,经常用作肠道抗感染剂。我们的研究旨在研究NFX对INDO诱导的肾毒性的肾脏保护作用,并探讨其保护机制。将四组大鼠分为(I)正常对照组,(II)NFX处理(50mg/kg),(III)INDO控制(20mg/kg),和(IV)NFX+INDO。NFX减轻INDO诱导的肾损伤中的肾损害,通过降低血清尿素水平证明,肌酐,尿酸,和NGAL,而白蛋白升高。NFX通过降低MDA水平和恢复由上调Nrf2、HO-1和细胞球蛋白途径介导的抗氧化剂GSH和SOD水平来减轻肾脏氧化应激。NFX减轻肾脏炎症,有效降低MPO,IL-1β,NADPH氧化酶和NF-κB表达的显著下调以及JAK-1和STAT3磷酸化的抑制介导的大鼠肾脏中TNF-α水平。NFX通过降低裂解的caspase-3表达来减轻肾细胞凋亡。总之,NFX治疗通过调节Nrf2/HO-1,细胞球蛋白,NADPH-氧化酶,NF-κB,和JAK-1/STAT3信号。
    Indomethacin (INDO) is an NSAID with remarkable efficacy and widespread utilization for alleviating pain. Nevertheless, renal function impairment is an adverse reaction linked to INDO usage. Nifuroxazide (NFX), an oral nitrofuran antibiotic, is frequently employed as an intestinal anti-infective agent. Our study aimed to investigate the renoprotective effects of NFX against INDO-induced nephrotoxicity and explore the protection mechanisms. Four groups of rats were allocated to (I) the normal control, (II) the NFX-treated (50 mg/kg), (III) INDO control (20 mg/kg), and (IV) NFX + INDO. NFX attenuates renal impairment in INDO-induced renal injury, proved by decreasing serum levels of urea, creatinine, uric acid, and NGAL while the albumin was elevated. NFX mitigates renal oxidative stress by decreasing MDA levels and restoring the antioxidants\' GSH and SOD levels mediated by upregulating Nrf2, HO-1, and cytoglobin pathways. NFX mitigated renal inflammation and effectively decreased MPO, IL-1β, and TNF-α levels in the rat\'s kidney mediated by significant downregulation of NADPH-oxidase and NF-κB expression and suppression of JAK-1 and STAT3 phosphorylation. NFX mitigates renal apoptosis by decreasing the expression of cleaved caspase-3 expression. In conclusion, NFX treatment prevents INDO nephrotoxicity by regulating Nrf2/HO-1, cytoglobin, NADPH-oxidase, NF-κB, and JAK-1/STAT3 signals.
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  • 文章类型: Journal Article
    糖尿病(DM)的患病率在世界范围内惊人地增加。糖尿病视网膜病变(DR)是一种常见的DM微血管并发症,代表了劳动年龄人口失明的主要原因。炎症是DR发病机制中至关重要的参与者。JAK/STAT3轴为多向级联,其调节多种炎症事件。Nifuroxazide(Nifu)是一种常用的口服抗生素,据报道具有JAK/STAT3抑制活性。本研究调查了Nifu对糖尿病引起的视网膜损伤的潜在保护作用。Nifu对氧化应激的影响,还研究了JAK/STAT3轴和下游炎症介质。通过单次腹膜内注射链脲佐菌素(50mg/kg)在SpragueDawley大鼠中诱发糖尿病。将动物分为四组:正常,Nifu控制,DM,和DM+Nifu。Nifu以25mg/kg/天口服给药8周。尼复对氧化应激的影响,JAK/STAT3轴蛋白,炎症因子,紧密连接蛋白,组织学,和超微结构改变使用分光光度法进行评估,基因和蛋白质分析,和组织学研究。对糖尿病大鼠的Nifu给药减轻了组织病理学和视网膜损伤的迹象。此外,Nifu减弱了视网膜氧化应激,抑制JAK和STAT3磷酸化,上调STAT3信号抑制因子SOCS3的表达,抑制炎症因子NF-κB的表达,和炎性细胞因子TNF-α。总的来说,目前的研究表明,尼复减轻了糖尿病大鼠的DR进展,表明有益的视网膜保护作用。这可以归因于阻断视网膜组织中的JAK/STAT3轴,随后氧化应激和炎症的改善。
    The prevalence of diabetes mellitus (DM) is alarmingly increasing worldwide. Diabetic retinopathy (DR) is a prevailing DM microvascular complication, representing the major cause of blindness in working-age population. Inflammation is a crucial player in DR pathogenesis. JAK/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on oxidative stress, JAK/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM + Nifu. Nifu was orally administrated at 25 mg/kg/day for 8 weeks. The effects of Nifu on oxidative stress, JAK/STAT3 axis proteins, inflammatory factors, tight junction proteins, histological, and ultrastructural alterations were evaluated using spectrophotometry, gene and protein analyses, and histological studies. Nifu administration to diabetic rats attenuated histopathological and signs of retinal injury. Additionally, Nifu attenuated retinal oxidative stress, inhibited JAK and STAT3 phosphorylation, augmented the expression of STAT3 signaling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB, and inflammatory cytokine TNF-α. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK/STAT3 axis in retinal tissues with subsequent amelioration of oxidative stress and inflammation.
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  • 文章类型: Journal Article
    目的:首次评价硝呋嗪(NIF)在皮肤衰老大鼠模型中的抗衰老特性,以建立有效的预防措施和抗衰老皮肤疗法。
    方法:将30只老年雄性大鼠随机分为3组,治疗NIFI,老年大鼠用NIF(10mg/kg,每天口服一次,连续14天),并治疗了NIFII,老年大鼠用NIF(20mg/kg,每天口服一次,连续14天)。从老年雄性大鼠的背部皮肤获得皮肤样本,并进行组织生化MDA处理,组织学(Hx&E和Masson\'s三色染色),和免疫组织化学(IL-6,NF-κB,和caspase-3)分析。
    结果:第一组老年雄性白化病大鼠皮肤表现出明显的表皮和真皮变形,胶原纤维的解体,真皮中胶原纤维的多个空间明显丢失,表皮总厚度和胶原纤维平均面积百分比显著减少,升高的组织MDA水平和强阳性的IL-6,NF-κB,和caspase-3免疫反应。NIF对皮肤老化的抗衰老益处通过组织良好的表皮和真皮形式的组织学改变的显着改善来证明。真皮中的大多数胶原纤维看起来紧密堆积,表皮总厚度和胶原纤维平均面积百分比显著升高,组织MDA水平显著下降,和炎症标志物的免疫表达,IL-6和NF-κB,和凋亡标志物caspase-3。
    结论:这项研究发现第III组,接受20mg/kg的NIF,经历了比II组更明显和更明显的皮肤老化改善,其中接受了10mg/kg的NIF。
    OBJECTIVE: To evaluate nifuroxazide\'s (NIF\'s) anti-aging characteristics in a skin-aging rat model for the first time in order to create effective preventive measures and anti-aging skin therapies.
    METHODS: Thirty randomly selected aged male rats were assorted into three equal groups; aged control group, treated NIF I, aged rats were treated with NIF (10mg/kg, orally once daily for 14 consecutive days), and treated NIF II, aged rats were treated with NIF (20mg/kg, orally once daily for 14 consecutive days). Skin samples were obtained from the dorsal skin of the aged male rats and processed for tissue biochemical MDA, histological (Hx&E and Masson\'s Trichrome stains), and immunohistochemical (IL-6, NF-κB, and caspase-3) analysis.
    RESULTS: Group I aged male albino rat skin illustrated evident distorted epidermis and dermis, disorganization of collagen fibers with marked multiple spaces of collagen fibers loss in the dermis, marked reduction of total epidermal thickness and mean area percent of collagen fibers, elevated tissue MDA level and strong positive IL-6, NF-κB, and caspase-3 immune reaction. The anti-aging benefits of NIF on skin aging are demonstrated by a marked improvement in histological alterations in the form of a well-organized epidermis and dermis, most collagen fibers in the dermis appear closely packed, significant elevation of total epidermal thickness and mean area percent of collagen fibers, a significant decrease of tissue MDA level, and immunoexpression of the inflammatory markers, IL-6, and NF-κB, and the apoptotic marker caspase-3.
    CONCLUSIONS: This study found that group III, which received 20mg/kg of NIF, experienced more pronounced and noticeable improvements in skin aging than group II, which received 10mg/kg of NIF.
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  • 文章类型: Journal Article
    硝呋嗪(NFX)是一种安全的硝基呋喃抗菌药物,临床上用于治疗急性腹泻和传染性旅行者腹泻或结肠炎。最近的研究表明,NFX表现出多种药理作用,包括抗癌,抗氧化剂,和抗炎作用。NFX在抑制甲状腺,乳房,肺,膀胱,肝脏,结肠癌和骨肉瘤,黑色素瘤,和其他通过抑制STAT3以及ALDH1,MMP2,MMP9,Bcl2和上调Bax介导的。此外,它对脓毒症诱导的器官损伤有很好的效果,肝脏疾病,糖尿病肾病,溃疡性结肠炎,和免疫性疾病。这些有希望的作用似乎是通过抑制STAT3以及NF-κB介导的,TLR4和β-catenin表达并有效降低下游细胞因子TNF-α,IL-1β,IL-6我们的综述总结了有关NFX在癌症和其他疾病中的分子生物学机制的现有研究,建议将这些研究转化为实验动物和培养细胞,并在各种疾病中重新利用NFX,以获得基于人类研究的科学证据。
    Nifuroxazide (NFX) is a safe nitrofuran antibacterial drug used clinically to treat acute diarrhea and infectious traveler diarrhea or colitis. Recent studies revealed that NFX displays multiple pharmacological effects, including anticancer, antioxidant, and anti-inflammatory effects. NFX has potential roles in inhibiting thyroid, breast, lung, bladder, liver, and colon cancers and osteosarcoma, melanoma, and others mediated by suppressing STAT3 as well as ALDH1, MMP2, MMP9, Bcl2 and upregulating Bax. Moreover, it has promising effects against sepsis-induced organ injury, hepatic disorders, diabetic nephropathy, ulcerative colitis, and immune disorders. These promising effects appear to be mediated by suppressing STAT3 as well as NF-κB, TLR4, and β-catenin expressions and effectively decreasing downstream cytokines TNF-α, IL-1β, and IL-6. Our review summarizes the available studies on the molecular biological mechanisms of NFX in cancer and other diseases and it is recommended to translate the studies in experimental animals and cultured cells and repurpose NFX in various diseases for scientific evidence based on human studies.
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  • 文章类型: Journal Article
    背景:黑色素瘤,一种高度恶性的皮肤癌,是肿瘤治疗研究的热门话题。如今,肿瘤免疫治疗,特别是免疫疗法与其他疗法的结合,引起了越来越多的关注。吲哚胺2,3-双加氧酶2(IDO2),免疫抑制犬尿液中色氨酸代谢途径的一种酶,在黑色素瘤组织中高度表达。此外,IDO2显著抑制机体抗肿瘤免疫,已成为黑色素瘤治疗的新靶点。硝呋嗪,作为一种肠道抗菌剂,发现能够抑制Stat3表达并发挥抗肿瘤作用。因此,本研究旨在检查自行设计的IDO2-小干扰RNA(siRNA)通过减毒沙门氏菌联合硝呋嗪对黑素瘤小鼠的治疗效果,以及确定其潜在机制。
    方法:用流式细胞术检测硝呋嗪对黑色素瘤的影响,CCK-8和集落形成能力测定,分别,在体外。构建siRNA-IDO2质粒,建立小鼠黑素瘤模型。治疗后,监测肿瘤生长和存活率,HE染色检测肿瘤组织的形态学变化。Westernblotting检测相关蛋白的表达,IHC和IF检测肿瘤组织中CD4和CD8阳性T细胞的表达,流式细胞术检测脾脏中CD4和CD8阳性T细胞的比例。
    结果:结果表明,联合治疗可有效抑制黑色素瘤细胞中Stat3的磷酸化和IDO2的表达水平,能有效抑制肿瘤生长,延长荷瘤小鼠的生存时间。机械研究表明,与对照组和单药治疗组相比,联合治疗组减少了肿瘤细胞的异型性,增加了凋亡率,增强肿瘤组织中T淋巴细胞的浸润,增加脾脏中的CD4+和CD8+T淋巴细胞,提示其机制可能与抑制肿瘤细胞增殖有关,细胞凋亡的增加和细胞免疫的增强。
    结论:结论:IDO2-siRNA联合nifuroxazide治疗可在黑素瘤小鼠的治疗中发挥重要作用。提高肿瘤免疫力,为临床上寻找治疗黑色素瘤的新组合方法提供实验依据。
    Melanoma, a highly malignant skin cancer, is a hot topic in oncology treatment research. Nowadays, tumor immunotherapy, especially immunotherapy combined with other therapies, has attracted more and more attention. Indoleamine 2,3-dioxygenase 2 (IDO2), a ratelimiting enzyme of the tryptophan metabolism pathway in the urine of dogs with immunosuppression, is highly expressed in melanoma tissue. Additionally, IDO2 significantly inhibits the anti-tumor immunity of the body and has become a novel target of melanoma treatment. Nifuroxazide, as an intestinal antibacterial agent, was found to be able to inhibit Stat3 expression and exert an anti-tumor effect. Therefore, the present study aimed to examine the therapeutic effect of a self-designed IDO2-small interfering RNA (siRNA) delivered by attenuated Salmonella combined with nifuroxazide on melanoma- bearing mice, as well as determine its underlying mechanism.
    The effect of nifuroxazide on melanoma was detected by flow cytometry, CCK-8 and colony- forming ability assays, respectively, in vitro. The plasmid of siRNA-IDO2 was constructed, and the mice-bearing melanoma model was established. After the treatment, the tumor growth and survival rate were monitored, and the morphological changes of tumor tissue were detected by HE staining. The expression of related proteins was detected by Western blotting, and the expression of CD4 and CD8 positive T cells in tumor tissue was detected by IHC and IF, and the proportion of CD4 and CD8 positive T cells in spleen was detected by flow cytometry.
    The results demonstrated that the combination therapy effectively inhibited the phosphorylation of Stat3 and the expression level of IDO2 in melanoma cells, which effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. The mechanistic study revealed that, compared with control groups and monotherapy groups, the combination treatment group reduced the atypia of tumor cells, increased the apoptotic rate, enhanced the infiltration of T lymphocytes in tumor tissue and increased the CD4+ and CD8+ T lymphocytes in the spleen, suggesting that the mechanism may be associated with the inhibition of tumor cell proliferation, the increase of apoptosis and the enhancement of the cellular immunity.
    In conclusion, IDO2-siRNA combined with nifuroxazide therapy could serve a significant role in the treatment of melanoma-bearing mice, enhance the tumor immunity and provide an experimental basis for identifying a novel combination method for the treatment of melanoma clinically.
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  • 文章类型: Journal Article
    UNASSIGNED: Acute gastroenteritis remains an extremely common problem among the general population. In Western countries, an average person will probably face one or two episodes of gastrointestinal infections every year.
    UNASSIGNED: The aim of this study was to compare the efficacy of nifuroxazide and probiotic preparation containing lactic acid bacteria in the treatment of acute diarrheal syndrome.
    UNASSIGNED: The study was prospective, comparative study. Patients who suffered from acute infective diarrhoea for ≤72 hours and had ≥3 unformed stools per day, with no administration of antibiotics during 10 days before enrolment were divided into two groups: nifuroxazide group and the lactic acid probiotic group. All patients received therapies four times a day for three days. Data was collected at the baseline visit (before the initiation of the treatment) and two follow-up examinations on the third and seventh day from the treatment start.
    UNASSIGNED: The study included 61 patients, 36 in nifuroxazide group and 25 in probiotic group. Nifuroxazide group compared to probiotic group showed faster improvement of patients\' condition with lower number of stools three and seven days after therapy start (p=0.001 and p<0.001 respectively) and faster stool consistency normalization. On the seventh day from therapy start medium mushy stool consistency was observed in the majority of patients in nifuroxazide group (n=31, 86%) and only in small number of patients in probiotic group (n=5, 20%). Patients were feeling better and there was a trend of reporting better therapy efficacy in nifuroxazide group. Subjective assessment of therapy tolerability was also better in nifuroxazide group. Compliance to therapy and recommended dietary regime was similar between groups and there were no significant differences between groups regarding age, gender, elevated body temperature, abdominal pain, cramps, nausea and vomiting.
    UNASSIGNED: Although probiotics are sometimes used in the treatment of acute diarrheal syndrome, nifuroxazide has better efficacy and greater patients\' satisfaction. Nifuroxazide can be recommended as the first choice empirical treatment in adult patients with the acute diarrheal syndrome.
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