Interferon-α2b

干扰素 - α 2b
  • 文章类型: Case Reports
    Erdheim-Chester病(ECD)是一种罕见的组织细胞增生症,其特征是受影响器官的黄瘤浸润。我们介绍了一例62岁的ECD患者,最初表现为缩窄性心包炎。综合影像学显示全身受累,包括骷髅,轨道,垂体,肺,肾,和腹膜后,尽管没有相关症状。通过CT引导活检的组织病理学证据最终证实了ECD的诊断。患者对干扰素-α2b治疗反应良好,在5个月的随访期内,症状逐渐改善,影像学和实验室检查结果也有所改善。该病例强调了在缩窄性心包炎的鉴别诊断中考虑ECD的重要性,以及多模态成像对这种罕见疾病的准确诊断和治疗的实用性。患者对治疗的积极反应也突出了有效管理ECD的潜力,特别是早期诊断和干预。
    Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by xanthomatous infiltration of affected organs. We present a case of a 62-year-old man with ECD initially presenting with constrictive pericarditis. Comprehensive imaging revealed systemic involvement, including the skeleton, orbit, pituitary, lung, kidney, and retroperitoneum, despite the absence of related symptoms. The diagnosis of ECD was eventually confirmed through histopathological evidence from a CT-guided biopsy. The patient responded well to interferon-α2b treatment, with gradual symptom amelioration and improvement in imaging and laboratory findings over a 5-month follow-up period. This case highlights the importance of considering ECD in the differential diagnosis of constrictive pericarditis and the utility of multimodal imaging for accurate diagnosis and management of this rare disease. The patient\'s positive response to treatment also highlights the potential for effective management of ECD, particularly with early diagnosis and intervention.
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  • 文章类型: Journal Article
    先前的研究表明,形状复杂的纳米粒子(NP)在毫米范围内具有固有的辐射热发射。本文介绍了一种基于检测其固有放射热发射的方法来控制纳米药物-免疫生物制剂(IBP)的质量。干扰素(IFN)药物的发射率,在不打开初级包装的情况下确定,如下(µW/m2):IFN-α2b-80±9(每包105IU),IFN-β1a-40±5(每包24×106IU),IFN-γ-30±4(每包105IU)。病毒样颗粒(VLP)的发射率,使用注射瓶(卷曲盖小瓶)中的疫苗Gam-VLP-multivac(120μg)测定,如下:12±1µW/m2,Gam-VLP-rota疫苗-9±1µW/m2。这项研究显示了一年内发射率的可重复性,免疫生物产品的储存条件。已经表明,加速老化和更长的保质期伴随着活性NP的凝结,导致发射率下降很多倍。辐射热发射对温度的依赖性很复杂,非单调性。发射强度取决于剂量的形式,但仍在大小为IFN-α2b的鼻内水溶液,软膏,和栓剂.已经在实验动物中证明了对VLP疫苗的鼻内施用的免疫应答的第一阶段(IFN的合成增加)的远程定量控制的可能性。
    Previous studies have shown that complexly shaped nanoparticles (NPs) have their intrinsic radiothermal emission in the millimeter range. This article presents a method for controlling the quality of nanodrugs-immunobiological preparations (IBPs)-based on the detection of their intrinsic radiothermal emissions. The emissivity of interferon (IFN) medicals, determined without opening the primary package, is as follows (µW/m2): IFN-α2b-80 ± 9 (105 IU per package), IFN-β1a-40 ± 5 (24 × 106 IU per package), IFN-γ-30 ± 4 (105 IU per package). The emissivity of virus-like particles (VLP), determined using vaccines Gam-VLP-multivac (120 μg) in an injection bottle (crimp cap vials), was as follows: 12 ± 1 µW/m2, Gam-VLP-rota vaccines-9 ± 1 µW/m2. This study shows the reproducibility of emissivity over the course of a year, subject to the storage conditions of the immunobiological products. It has been shown that accelerated aging and a longer shelf life are accompanied by the coagulation of active NPs, and lead to a manyfold drop in emissivity. The dependence of radiothermal emission on temperature has a complex, non-monotonic nature. The emission intensity depends on the form of dosage, but remains within the order of magnitude for IFN-α2b for intranasal aqueous solution, ointments, and suppositories. The possibility of the remote quantitative control of the first phases of the immune response (increased synthesis of IFNs) to the intranasal administration of VLP vaccines has been demonstrated in experimental animals.
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  • 文章类型: Journal Article
    目的:本研究旨在评估椎旁注射重组人干扰素-α2b与高压,DRG中的长期脉冲射频(PRF)缓解带状疱疹后神经痛(PHN)。
    方法:这项回顾性研究是对84例急性PHN患者进行的。参与者分为三组。H组:干扰素-α2b联合高电压长期PRF治疗;C组:高电压长期PRF治疗;I组:干扰素-α2b治疗。3组患者均在治疗过程中出现阵阵疼痛时口服盐酸吗啡速释片5mg。疼痛数字评分(NRS),在治疗之前和之后记录IL-6、Gal-3和PHN的发生率。
    结果:治疗后所有个体的疼痛强度均降低。与C组比较,H组NRS评分在治疗后4、8和12周时显著降低,PHN发生率明显较低。与之前的治疗相比,H组减少了加巴喷丁胶囊和盐酸吗啡速释片的推荐剂量。与C组相比,H组口服加巴喷丁胶囊和盐酸吗啡治疗后明显减少。三组患者均未出现严重不良反应。
    结论:在治疗急性PHN的背景下,干扰素-α2b的注射结合高电压,PRF的长期应用比PRF或单独注射干扰素-α2b更有效。
    This investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term, pulsed radiofrequency (PRF) in the dorsal root ganglion for the mitigation of postherpetic neuralgia (PHN).
    This retrospective study included 84 individuals with acute PHN. The participants were divided into 3 groups. Group H was treated with interferon-α2b combined with high-voltage long-term PRF. Group C was treated with a combination of high-voltage, long-term PRF and a paravertebral injection (without recombinant human interferon-α2b), and group I was treated with interferon-α2b only. All the patients in the 3 groups were orally administered a 5-mg morphine hydrochloride quick-release tablet when a burst of pain occurred during treatment. The numerical rating scale for pain score, the interleukin-6 and galectin-3 levels, and the incidence of PHN were documented before and after therapy.
    The pain intensity of all individuals decreased after therapy. Compared with group C, the numerical rating scale scores for group H were significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lower. Compared with prior treatment, the recommended dosage of gabapentin capsules and immediate-release morphine hydrochloride tablets was reduced for group H. Compared with group C, the requirement for orally administrated gabapentin capsules and morphine hydrochloride tablets in group H was reduced significantly after treatment. No serious adverse reactions occurred in any of the 3 groups.
    Within the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than PRF or the injection of interferon-α2b alone.
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  • 文章类型: Journal Article
    增生性瘢痕(HS)是一种严重的皮肤纤维化疾病,发病机制尚不清楚。干扰素-α2b(IFN-α2b)在体内和体外对HS具有抑制作用;然而,确切的机制尚不清楚。在这项研究中,我们旨在评估IFN-α2b对增生性瘢痕成纤维细胞(HSF)增殖和迁移的抑制作用,并进一步探讨相关的分子机制。细胞计数试剂盒-8和CyQUANT测定用于评估HSF的增殖;伤口愈合和Transwell测定用于评估HSF的迁移;实时定量聚合酶链反应和蛋白质印迹用于检测信使RNA和蛋白质水平,分别,相关基因;进行生物信息学分析以预测IFN-α2b的下游靶标。我们的发现如下:(1)IFN-α2b以剂量依赖性方式抑制HSF的增殖和迁移。(2)IFN-α2b通过抑制Wnt/β-catenin通路抑制HSF的增殖和迁移。(3)视黄酸受体应答者3(RARRES3)被预测为IFN-α2b的功能性下游分子,在HSF中很低。(4)IFN-α2b通过上调RARRES3表达抑制HSF表型和Wnt/β-catenin通路。(5)RARRES3通过抑制Wnt/β-catenin通路抑制HSF的增殖和迁移。总之,IFN-α2b诱导的RARRES3上调通过Wnt/β-catenin通路抑制抑制HSF增殖和迁移。
    Hypertrophic scar (HS) is a severe skin fibrotic disorder with unclear pathogenesis. Interferon-α2b (IFN-α2b) exerts inhibitory effects on HS in vivo and in vitro; however, the exact mechanism remains unclear. In this study, we aimed to evaluate the inhibitory effects of IFN-α2b on hypertrophic scar fibroblasts\' (HSFs) proliferation and migration, and to further investigate the associated molecular mechanism. Cell Counting Kit-8 and CyQUANT assays were used to assess HSFs\' proliferation; wound healing and Transwell assays were used to assess HSFs\' migration; real-time quantitative polymerase chain reaction and Western blotting were used to detect messenger RNA and protein levels, respectively, of related genes; bioinformatics analysis was performed to predict the downstream target of IFN-α2b. Our findings are as follows: (1) IFN-α2b inhibited HSFs\' proliferation and migration in a dose-dependent manner. (2) IFN-α2b inhibited HSFs\' proliferation and migration by suppressing the Wnt/β-catenin pathway. (3) Retinoic-acid receptor responder 3 (RARRES3) was predicted as a functional downstream molecule of IFN-α2b, which was low in HSFs. (4) IFN-α2b inhibited HSF phenotypes and the Wnt/β-catenin pathway by upregulating RARRES3 expression. (5) RARRES3 restrained HSFs\' proliferation and migration by repressing the Wnt/β-catenin pathway. In conclusion, IFN-α2b-induced RARRES3 upregulation inhibited HSFs\' proliferation and migration through Wnt/β-catenin pathway suppression.
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  • 文章类型: Journal Article
    当前2019年冠状病毒病(COVID-19)的爆发已在全球迅速蔓延。治疗期间,我们发现大多数患者的血红蛋白(Hb)下降.干扰素-α2b(IFN-α2b)是与Hb降低有关的主要可疑药物。因此,本研究旨在探讨IFN-α2b是否能诱导COVID-19重症患者Hb降低及其可能的机制。
    2月12日至24日,哈尔滨医科大学附属第一医院收治的50例COVID-19重症感染患者,2020年。人口统计,基线特征,临床资料,回顾性收集治疗方案。根据第14天IFN-α2b的使用减少,将患者分为两组。入院时的Hb水平,收集并分析第7天,第14天和第21天.主要终点是第21天的Hb水平。
    对IFN-停止组31例患者和非IFN-停止组19例患者进行了回顾。年龄,性别,合并症,临床症状,营养状况,疾病严重程度,并发症,和患者的其他因素进行比较,IFN停止组和非IFN停止组之间无差异.与入院时相比,所有患者的Hb水平在第7天显着降低(p<0.0001)。在IFN停止组中,Hb水平在IFN-α2b停止后7天增加(p=.0008),而在非IFN停止组的第14天和第21天之间没有发现差异(p=.3152)。
    在COVID-19重症患者的治疗中,IFN-α2b与Hb降低相关。临床医生应该意识到IFN-α2b治疗的患者Hb降低的高发生率。
    UNASSIGNED: The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism.
    UNASSIGNED: A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12th to 24th, 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21.
    UNASSIGNED: A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission (p < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped (p = .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group (p = .3152).
    UNASSIGNED: IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.
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  • 文章类型: Journal Article
    UNASSIGNED: The exhaustion and poor homing of activated lymphocytes are critical obstacles in adoptive cell immunotherapy for solid tumors. In order to effectively deliver immune cells into tumors, we encapsulated interferon-α2b (IFN-α2b) into macroporous hydrogels as an enhancement factor and utilized low-dose irradiation (LDI) as a tumoral attractor of T cells.
    UNASSIGNED: Hydroxypropyl cellulose hydrogels were prepared by irradiation techniques, and the cross-sectional microstructure was characterized by scanning electron microscopy. The synergistic antitumor mechanism of combination of IFN-α2b and CIK cells was evaluated by detecting the expression of activation marker CD69 on CIK cell surface and IFN-γ production by CIK cells. The in vivo antitumor activity of IFN-α2b-incorporated hydroxypropyl cellulose hydrogels combined with CIK and radiation was evaluated in an MKN-45 xenografted nude mice model.
    UNASSIGNED: The bioactivity of IFN-α2b was well maintained in ultraviolet-reactive, rapidly cross-linkable hydroxypropyl cellulose hydrogels. In vitro studies demonstrated IFN-α2b-activated T cells, as evidenced by upregulating early activation marker CD69 and secretion inflammatory cytokine IFN-γ. In vivo real-time image showed our hydrogels kept a higher amount of drug delivery at the tumor site for a long time compared with free drug injection. Low-dose irradiation promoted T cell accumulation and infiltration in subcutaneous tumors. Combination of IFN-α2b-loaded hydrogels (Gel-IFN) with T cells and LDI exhibited higher efficacy to eradicate human gastric cancer xenograted tumors with less proliferating cells and more necrotic regions compared with IFN-α2b or T cells alone.
    UNASSIGNED: HPC hydrogels kept the activity of IFN-α2b and stably release of IFN-α2b to stimulate T cells for a long time. At the same time, low-dose radiation recruits T cells into tumors. This innovative integration mode of IFN-α2b-loaded hydrogels and radiotherapy offers a potent strategy to improve the therapeutic outcome of T cell therapy.
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  • 文章类型: Journal Article
    Ocular surface squamous neoplasia is the most common tumour of the ocular surface. It is a spectrum of disease from intraepithelial dysplasia to invasive squamous cell carcinoma. Recent years have seen an increase in the use of topical chemotherapeutic agents to treat this condition, often as primary treatment without full-thickness biopsy. This practical approach provides a critical appraisal of the evidence base with the goal being to aid the clinician in the management of these patients.
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  • 文章类型: Journal Article
    BACKGROUND: Interferon-α2b is FDA approved drug for the treatment of chronic HCV and HBV, melanoma, AIDS-related KS, carcinomas, hairy cell leukemia and chronic myelogenous leukemia. However, administration of interferon-α2b to patients takes place thrice in a week due to short in vivo circulation half-life.
    OBJECTIVE: To extend the circulation half-life of IFN-α2b, it is conjugated with polyethylene glycol (PEG). However, PEGylation may results in reduction of its antiviral and antiproliferative activities but on the other side, it results in prolonged plasma half-life.
    METHODS: Human interferon-α2b was PEGylated with linear 20kDa methoxypolyethlene glycol (mPEG) Propionaldehyde (IFN-Ald20K), Y-Shaped 40kDa mPEG-Propionaldehyde (IFNAld40K), linear 20-kDa mPEG-Succinimidyl Succinate (IFN-NHS20K), and Y shaped 40kDa mPEG-Succinimidyl Succinate (IFN-NHS40K). Impact of PEG size, shape and PEGylation site was studied to establish their relationship with antiprolifetaive activities and serum retention time of PEGylated IFN-α2b.
    RESULTS: RP-HPLC studies showed that larger PEGs (40kDa) increased the hydrodynamic volume and increased the serum retention time while antiproliferative activity in HepG2 cell line was decreased with increase in PEGylated interferon-α2b size. Molecular docking results also dictated the same effect that increase in PEGylated interferon-α2b size results in steric shielding of the receptor-binding site on interferon-α2b. IFN-Ald20K showed highest (45%) biological activity with serum half-life 40 hours while IFN-NHS40K showed least (7%) biological activity with serum halflife 56 hours.
    CONCLUSIONS: Thus, IFN-Ald40K with 12% residual activity and 62 hours of serum half-life proved to be a potent candidate for anticancer and antiviral effect with enhanced serum retention time.
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  • 文章类型: Journal Article
    目的:本研究的目的是评估IFN-α2b直肠和局部剂型与抗氧化剂联合治疗急性呼吸道感染(ARIs)的临床和干扰素调节功效。
    方法:在发病后48小时内,共90名年龄为19.2±0.9岁的无复杂ARI军人住院。患者被随机分为3组,每组30人。在第一组中,患者接受含有IFN-α2b(1百万IU)和抗氧化剂(α-生育酚乙酸酯和抗坏血酸)的直肠栓剂,每日2次,共5天.在第二组中,除上述栓剂外,患者每天3次鼻内接受含有IFN-α2b(36000IU/1g)和抗氧化剂的凝胶制剂.在第三组中,患者接受200mg剂量的抗美非诺韦(参比药物),每日4次,共5天.不同组ARI临床表现消退的动态变化,血浆中IFN-α和IFN-γ浓度的变化,以及通过血细胞离体评价这些细胞因子的自发和诱导产生。之后,对患者再观察3个月,登记ARI住院的重复病例.
    结果:当鼻内剂型的IFN-α2b给予接受该细胞因子的直肠形式的患者时,观察到明显的加速中毒和发热症状消退的趋势。IFN-α2b的直肠和局部剂型与抗氧化剂的组合在预防ARI重复住院方面比直肠栓剂的单一疗法更有效。上述组合在其最初偏离标准时引起对离体血细胞诱导的IFN-α产生的最完全校正。
    结论:获得的数据表明使用IFN-α2b的直肠和局部剂型与抗氧化剂的组合治疗ARI的权宜之计。
    OBJECTIVE: The aim of the study was to evaluate the clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of IFN-α2b with antioxidants in the treatment of acute respiratory infections (ARIs) in comparison with other variants of antiviral therapy.
    METHODS: A total of 90 servicemen aged 19.2±0.9 years with uncomplicated forms of ARI were hospitalized not later than 48 hours after the onset of the disease. Patients were randomized into 3 groups of 30 people each. In the first group, patients received rectal suppositories containing IFN-α2b (1 million IU) and antioxidants (alpha-tocopherol acetate and ascorbic acid) twice a day for 5 days. In the second group, patients received intranasally a gel formulation containing IFN-α2b (36 000 IU/1 g) and antioxidants 3 times a day in addition to the above suppositories. In the third group, patients were prescribed umifenovir (reference drug) at dose of 200 mg 4 times a day for 5 days. The dynamics of regression of clinical manifestations of ARI in different groups, changes in concentrations of IFN-α and IFN-γ in blood plasma, as well as spontaneous and induced production of these cytokines by blood cells ex vivo were evaluated. After that, the patients were observed for another 3 months to register repeated cases of hospitalization for ARI.
    RESULTS: Marked tendency to accelerate the regression of symptoms of intoxication and fever was observed when intranasal dosage form of IFN-α2b was administered to patients receiving the rectal form of this cytokine. The combination of rectal and topical dosage forms of IFN-α2b with antioxidants was more effective than monotherapy with the rectal suppositories in preventing repeated hospitalization for ARI. The above combination caused the most complete correction of induced production of IFN-α by blood cells ex vivo at its initial deviation from the norm.
    CONCLUSIONS: The obtained data indicate the expediency of using the combination of rectal and topical dosage forms of IFN-α2b with antioxidants for treatment of ARI.
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  • 文章类型: Journal Article
    我们已经开发了用于体内生产O-糖基化蛋白质的大肠杆菌菌株。这是使用双重质粒方法实现的:一种编码治疗性蛋白质靶标,和第二个编码O-糖基化所需的酶机制。后一种质粒编码人多肽N-乙酰半乳糖胺基转移酶以及β1,3-半乳糖基转移酶和UDP-Glc(NAc)-4-差向异构酶,两者都来自空肠弯曲杆菌,和细菌或人类来源的二硫键异构酶。这种双质粒合成操纵子系统的有效性已在三种具有治疗潜力的蛋白质上进行了测试:天然O-糖基化人干扰素α-2b的天然和工程版本,以及具有一个糖基化工程位点的人类生长激素。已经建立了将核心1聚糖添加到蛋白质上的原理证明,我们现在正在开发该系统,作为在大肠杆菌中生产和修饰具有更复杂O-聚糖结构的人类蛋白质治疗剂的平台。
    We have developed an Escherichia coli strain for the in vivo production of O-glycosylated proteins. This was achieved using a dual plasmid approach: one encoding a therapeutic protein target, and a second encoding the enzymatic machinery required for O-glycosylation. The latter plasmid encodes human polypeptide N-acetylgalactosaminyl transferase as well as a β1,3-galactosyl transferase and UDP-Glc(NAc)-4-epimerase, both from Campylobacter jejuni, and a disulfide bond isomerase of bacterial or human origin. The effectiveness of this two-plasmid synthetic operon system has been tested on three proteins with therapeutic potential: the native and an engineered version of the naturally O-glycosylated human interferon α-2b, as well as human growth hormone with one engineered site of glycosylation. Having established proof of principle for the addition of the core-1 glycan onto proteins, we are now developing this system as a platform for producing and modifying human protein therapeutics with more complex O-glycan structures in E. coli.
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