Minocycline

米诺环素
  • 文章类型: Journal Article
    甲型流感病毒(IAV)在全球范围内造成大流行,流行病,和季节性爆发。由于循环基因型的不断变化,疫苗的年度修改成本很高,导致印度等低收入和中等收入国家的覆盖率不足。此外,IAV正在发展对批准的抗病毒药物的抵抗力,需要寻找替代疗法。在这项研究中,通过qRT-PCR定量病毒基因表达,在体外和体内评估FDA批准的抗生素米诺环素对IAV菌株的抗病毒作用。通过蛋白质印迹法检测病毒蛋白水平,和病毒滴度。我们的发现表明,无毒性剂量的米诺环素有效抑制IAV复制,无论病毒株或细胞系。其抗病毒机制通过靶向MEK/ERK信号通路独立于干扰素信号,这对于病毒核糖核蛋白(vRNP)的出口至关重要。米诺环素通过引起核内vRNP的积累来防止感染性病毒颗粒的组装和释放。此外,米诺环素还抑制IAV诱导的晚期细胞凋亡,进一步抑制病毒繁殖。米诺环素对IAV的抗病毒活性可以在流感带来的挑战和当前治疗的局限性中提供有希望的解决方案。
    Influenza A virus (IAV) poses a global threat worldwide causing pandemics, epidemics, and seasonal outbreaks. Annual modification of vaccines is costly due to continual shifts in circulating genotypes, leading to inadequate coverage in low- and middle-income countries like India. Additionally, IAVs are evolving resistance to approved antivirals, necessitating a search for alternative treatments. In this study, the antiviral role of the FDA-approved antibiotic minocycline against IAV strains was evaluated in vitro and in vivo by quantifying viral gene expression by qRT-PCR, viral protein levels by Western blotting, and viral titers. Our findings demonstrate that minocycline at a non-toxic dose effectively inhibits IAV replication, regardless of viral strain or cell line. Its antiviral mechanism operates independently of interferon signaling by targeting the MEK/ERK signaling pathway, which is crucial for the export of viral ribonucleoproteins (vRNPs). Minocycline prevents the assembly and release of infectious viral particles by causing the accumulation of vRNPs within the nucleus. Moreover, minocycline also inhibits IAV-induced late-stage apoptosis, further suppressing viral propagation. The antiviral activity of minocycline against IAVs could offer a promising solution amidst the challenges posed by influenza and the limitations of current treatments.
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  • 文章类型: Journal Article
    具有显著环境毒性的抗生素,例如,四环素(TC),经常在世界范围内大量使用,与50-80%的应用剂量最终在环境中。本研究旨在探讨盐酸四环素(TC)和盐酸米诺环素(MIN)对L.minor的影响。我们的研究通过分析植物生长和生物量以及评估同化色素水平和荧光来评估TC的植物毒性。该研究扩展了浮萍作为从水/废水中去除TC的工具的潜力。结果表明,两个TC都影响了Ir,Iy,生物量,和光合效率。浮萍对TC和MIN的吸收与生长培养基中的浓度成正比。TC更容易吸收,在最高浓度(19.2mg×L-1)下达到8.09mg×g-1的干重(DW),而MIN达到DW的6.01mg×g-1。如所示,TC对植物影响的后果略小,与MIN相比,虽然植物可以生物吸收这种药物,即使在最低的测试浓度。这项研究表明,使用植物进行药物生物吸附可以是水和废水处理的有效独立或补充方法。
    Antibiotics with significant environmental toxicity, e.g., tetracyclines (TCs), are often used in large quantities worldwide, with 50-80% of the applied dose ending up in the environment. This study aimed to investigate the effects of exposure to tetracycline hydrochloride (TC) and minocycline hydrochloride (MIN) on L. minor. Our research evaluated the phytotoxicity of the TCs by analyzing plant growth and biomass and evaluating assimilation pigment levels and fluorescence. The research was extended with the ability potential of duckweed as a tool for removing TCs from water/wastewater. The results demonstrated that both TCs influenced Ir, Iy, biomass, and photosynthetic efficiency. The uptake of TC and MIN by duckweed was proportional to the concentration in the growth medium. The TC was absorbed more readily, reaching up to 8.09 mg × g-1 of dry weight (DW) at the highest concentration (19.2 mg × L-1), while MIN reached 6.01 mg × g-1 of DW. As indicated, the consequences of the influence of TC on plants were slightly smaller, in comparison to MIN, while the plants could biosorb this drug, even at the lowest tested concentration. This study has shown that using plants for drug biosorption can be an effective standalone or complementary method for water and wastewater treatment.
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  • 文章类型: Case Reports
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  • 文章类型: Case Reports
    米诺环素,抗生素四环素的合成衍生物,已被用于各种医疗。米诺环素的一种这样的用途是用于寻常痤疮。虽然广泛使用,米诺环素具有组织变色的常见副作用,包括骨头,皮肤,和粘膜。该病例报告介绍了一名19岁的女性患者,该患者有长期接受米诺环素治疗的寻常痤疮病史,曾接受牙周美学牙冠延长术。初步检查显示粘膜呈蓝灰色变色。在手术探查后,发现变色起源于牙槽骨,牙龈受累最少。手术切除和重塑骨性外生骨显示骨仍深染。虽然变色的骨头没有完全切除,患者能够获得可接受的美学结果。
    Minocycline, the synthetic derivative of the antibiotic tetracycline, has been used for a variety of medical treatments. One such use for minocycline is for acne vulgaris. Although widely used, minocycline has a common side effect of discoloration of tissues, including bone, skin, and mucosa. This case report presents a 19-year-old female patient with a history of long-term minocycline therapy for acne vulgaris who presented for periodontal esthetic crown lengthening. The initial exam revealed a blue-gray discoloration of the mucosa. Upon surgical exploration, it was discovered that the discoloration originated from the underlying alveolar bone with minimal gingival involvement. Surgical removal and recontouring of the bony exostoses revealed that the bone remained deeply stained. Although the discolored bone was not fully removed, the patient was able to obtain an acceptable esthetic result.
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  • 文章类型: Journal Article
    蜱传脑炎(TBE)是由蜱传脑炎病毒(TBEV)引起的人畜共患疾病,影响人类和动物的中枢神经系统。目前,没有针对TBE患者的特定疗法,对症治疗是主要方法。在这项研究中,米诺环素(MIN)的作用,这是一种四环素抗生素,对TBEV感染的细胞系中的TBEV增殖和细胞保护进行了评估。间接免疫荧光,病毒滴度,RT-qPCR结果表明,用MIN处理48h后,TBEV复制以剂量依赖性方式被显著抑制。此外,研究了MIN对Vero细胞中不同TBEV感染复数(MOIs)的抑制作用。此外,转录组学分析和RT-qPCR结果表明,与MIN孵育后,TBEV和CALML4的水平降低,而钙通道受体的水平,如RYR2和SNAP25,均显著升高。MIN还调节MAPK-ERK相关因子,包括FGF2,PDGFRA,PLCB2和p-ERK,并抑制炎症反应。这些数据表明,向TBEV感染的细胞施用MIN可以降低TBEV水平,调节钙信号通路相关蛋白,抑制MAPK-ERK信号通路和炎症反应。这项研究为抗TBEV治疗的发展提供了创新的策略。
    Tick-borne Encephalitis (TBE) is a zoonotic disease caused by the Tick-borne Encephalitis virus (TBEV), which affects the central nervous system of both humans and animals. Currently, there is no specific therapy for patients with TBE, with symptomatic treatment being the primary approach. In this study, the effects of minocycline (MIN), which is a kind of tetracycline antibiotic, on TBEV propagation and cellular protection in TBEV-infected cell lines were evaluated. Indirect immunofluorescence, virus titers, and RT-qPCR results showed that 48 h post-treatment with MIN, TBEV replication was significantly inhibited in a dose-dependent manner. In addition, the inhibitory effect of MIN on different TBEV multiplicities of infection (MOIs) in Vero cells was studied. Furthermore, the transcriptomic analysis and RT-qPCR results indicate that after incubation with MIN, the levels of TBEV and CALML4 were decreased, whereas the levels of calcium channel receptors, such as RYR2 and SNAP25, were significantly increased. MIN also regulated MAPK-ERK-related factors, including FGF2, PDGFRA, PLCB2, and p-ERK, and inhibited inflammatory responses. These data indicate that administering MIN to TBEV-infected cells can reduce the TBEV level, regulate calcium signaling pathway-associated proteins, and inhibit the MAPK-ERK signaling pathway and inflammatory responses. This research offers innovative strategies for the advancement of anti-TBEV therapy.
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  • 文章类型: Journal Article
    由耐药鲍曼不动杆菌引起的感染不断增加,并导致显著的发病率和死亡率,尤其是住院和危重病人。鲍曼不动杆菌对许多抗生素迅速产生耐药性,传统上用于这种致命病原体的抗生素近年来一直在失败,强调需要确定新的治疗策略。已显示出希望的治疗选择包括重新审视通常不用于鲍曼不动杆菌的常见抗生素,评估最近上市的新抗生素,并确定显示协同相互作用的抗生素组合。在这项研究中,我们表征了广泛(XDR)和泛耐药(PDR)鲍曼不动杆菌患者分离株的抗生素敏感性。我们检查了22种标准护理抗生素和较新的抗生素埃拉环素的效力,omadacycline,和普拉佐米星对抗这些菌株。此外,我们针对我们的集合检查了这些抗生素的组合,以确定协同作用.我们发现该系列对大多数或所有标准治疗抗生素具有高度抗性,除了米诺环素和利福平.我们表明,基于最低抑制浓度,埃拉环素和奥马环素对这些菌株有效。我们还确定了两种高效的组合,头孢吡肟和阿米卡星,头孢吡肟和氨苄西林-舒巴坦,对这个集合表现出很高的协同作用。这些信息在我们对抗高度耐药和几乎无法治愈的鲍曼不动杆菌感染的斗争中很有价值。
    Infections due to drug-resistant Acinetobacter baumannii strains are increasing and cause significant morbidity and mortality, especially in hospitalized and critically ill patients. A. baumannii rapidly develops resistance to numerous antibiotics, and antibiotics traditionally used against this deadly pathogen have been failing in recent years, highlighting the need to identify new treatment strategies. Treatment options that have shown promise include revisiting common antibiotics not typically used against A. baumannii, evaluating new antibiotics recently introduced to market, and identifying combinations of antibiotics that display synergistic interactions. In this study, we characterized the antibiotic susceptibility profiles of extensively (XDR) and pandrug-resistant (PDR) A. baumannii patient isolates. We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains. Furthermore, we examined combinations of these antibiotics against our collection to identify synergistic effects. We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin. We show that eravacycline and omadacycline are effective against these strains based on minimum inhibitory concentrations. We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections.
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  • 文章类型: Journal Article
    我们的研究探索了整合米诺环素或伊立替康的胶原蛋白膜的发育,组织工程和药物递送系统中的靶向应用。I型胶原蛋白,使用先进的原纤维形成技术从牛皮中提取,与戊二醛交联以产生膜。这些膜掺入了米诺环素,抗生素,或者伊立替康,化疗药物,在各种浓度。膜,药物浓度不同,通过吸水和酶降解试验进行了研究,表现出一定程度的渗透性。我们强调局部给药治疗高级别胶质瘤的优势,强调靶向方法在减少全身不良反应和提高肿瘤部位药物生物利用度方面的功效。提出了利用胶原膜作为局部药物递送的可行方法。伊立替康的机制,拓扑异构酶I抑制剂,讨论了米诺环素的广谱抗菌作用和抑制胶质细胞诱导的细胞膜降解的作用。我们严格地研究了化疗药物的全身给药所带来的挑战,主要是由于血脑屏障的限制性,提倡局部给药方法作为胶质母细胞瘤治疗的更有效替代方法。这些本地交付策略,包括胶原膜,被认为是提高胶质母细胞瘤患者治疗效果的重大进展。
    Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach\'s efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan\'s mechanism, a topoisomerase I inhibitor, and minocycline\'s broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier\'s restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.
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  • 文章类型: Journal Article
    紫杉醇作为化疗药物的用途受到剂量依赖性紫杉醇诱导的神经性疼痛(PINP)发展的限制。最近,我们观察到,吲哚美辛联合米诺环素(IPM)以大麻素(CB)受体依赖性方式减弱小鼠模型中的PINP.吲哚美辛抑制环氧合酶(COX)活性,二甲胺四环素抑制5-脂氧合酶(5-LOX)活性。用吲哚美辛治疗紫杉醇引起的机械性异常性疼痛的雄性SpragueDawley大鼠,米诺环素,IPM组合,licofelone(一种双重COX/LOX抑制剂),或他们的车辆。AM251,CB1受体拮抗剂,和AM630,一种CB2受体拮抗剂,在IPM组合或利科非酮之前给药。使用动态足底美学计测量机械异常性疼痛。使用CB-Dock2进行分子对接。Licofelone和IPM组合具有抗痛觉过敏作用,显着高于单独的吲哚美辛或米诺环素。AM251和AM630阻断了IPM组合和利科非酮的抗痛觉过敏作用。分子对接表明,与植物大麻素1-反式-δ-9-四氢大麻酚和合成大麻素WIN55,212-2相似,利科芬酮与CB1和CB2受体均具有高亲和力。Licofelone在PINP大鼠模型中抑制COX和LOX和/或直接与CB受体相互作用以产生抗痛觉异常作用。研究结果进一步表明,licofelone可能是管理PINP的治疗剂。
    The use of paclitaxel as a chemotherapeutic drug is limited by the development of dose-dependent paclitaxel-induced neuropathic pain (PINP). Recently, we observed that the combination of indomethacin plus minocycline (IPM) attenuates PINP in a mouse model in a cannabinoid (CB) receptor-dependent manner. Indomethacin inhibits cyclooxygenase (COX) activity, and minocycline inhibits 5-lipoxygenase (5-LOX) activity. Male Sprague Dawley rats with paclitaxel-induced mechanical allodynia were treated with indomethacin, minocycline, IPM combination, licofelone (a dual COX/LOX inhibitor), or their vehicles. AM251, a CB1 receptor antagonist, and AM630, a CB2 receptor antagonist, were administered before the IPM combination or licofelone. Mechanical allodynia was measured using a dynamic plantar aesthesiometer. Molecular docking was performed using CB-Dock2. Licofelone and IPM combination had antiallodynic effects, which were significantly higher than either indomethacin or minocycline alone. AM251 and AM630 blocked the antiallodynic effects of IPM combination and licofelone. Molecular docking showed that licofelone binds to both CB1 and CB2 receptors with a high affinity similar to the phytocannabinoid 1-trans-delta-9-tetrahydrocannabinol and the synthetic cannabinoid WIN 55,212-2. Licofelone inhibits COX and LOX and/or directly interacts with CB receptors to produce antiallodynic effects in a rat model of PINP. The findings further suggest that licofelone could be a therapeutic agent for managing PINP.
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  • 文章类型: Journal Article
    背景:由鲍曼不动杆菌引起的感染是医院环境中健康问题的主要原因。此外,鲍曼不动杆菌的极端耐药性的存在使得治疗方案变得更具挑战性,因为治疗方案有限,因此鼓励研究人员探索现有的抗菌药物来对抗由它们引起的感染.这项研究的重点是多药耐药鲍曼不动杆菌(MDR-AB)菌株对米诺环素和粘菌素的敏感性。
    方法:从2022年6月至2023年6月进行了横断面研究。从各种临床样本中获得的100株鲍曼不动杆菌被送往中央实验室,微生物学系,SreeBalaji医学院和医院,Chrompet,钦奈,印度。根据临床和实验室标准协会(CLSI)指南进行抗菌药物敏感性测试,2022年。对于标准抗生素,进行了圆盘扩散法。对于米诺环素和粘菌素,最小抑制浓度(MIC)采用ε-silometer试纸条(E-strip)测定.
    结果:在这项研究中,获得了100株鲍曼不动杆菌,83%的分离株具有多重耐药性。在MDR-AB中,50(60%)对米诺环素敏感,40(48%)对粘菌素敏感。在40株对粘菌素敏感的鲍曼不动杆菌菌株中,29例(73%)对米诺环素易感,P值<0.05具有统计学意义。在43株粘菌素抗性鲍曼不动杆菌中,21例(53%)对米诺环素易感,P值<0.05具有统计学意义。
    结论:当考虑到治疗产生碳青霉烯酶的革兰氏阴性菌的费用时,粘菌素和二甲胺四环素可以用作替代药物,因为它们副作用更少,更实惠。米诺环素可以用作粘菌素的替代品,因为它可以从可注射制剂转化为口服制剂。
    BACKGROUND: Infections caused by Acinetobacter baumannii are a major cause of health concerns in the hospital setting. Moreover, the presence of extreme drug resistance in A. baumannii has made the scenario more challenging due to limited treatment options thereby encouraging the researchers to explore the existing antimicrobial agents to combat the infections caused by them. This study focuses on the susceptibility of multi-drug-resistant A. baumannii (MDR-AB) strains to minocycline and also to colistin.
    METHODS: A cross-sectional study was conducted from June 2022 to June 2023. One hundred isolates of​​​​​​ A. baumannii ​​​obtained from various clinical samples were sent to Central Laboratory, Department of Microbiology, Sree Balaji Medical College and Hospital, Chrompet, Chennai, India. The antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, 2022. For the standard antibiotics, the disc diffusion method was performed. For minocycline and colistin, the minimum inhibitory concentration (MIC) was determined using an epsilometer strip (E-strip) test.
    RESULTS: In this study, 100 isolates of A. baumannii were obtained, and 83% of the isolates were multi-drug-resistant. Among the MDR-AB, 50 (60%) were susceptible to minocycline and 40 (48%) were susceptible to colistin. Out of the 40 colistin-susceptible A. baumannii strains, 29 (73%) were susceptible to minocycline with a statistically significant P-value of <0.05. Among the 43 colistin-resistant A. baumannii strains, 21 (53%) were susceptible to minocycline with a statistically significant P-value of <0.05.
    CONCLUSIONS: When taking into account the expense of treating carbapenemase-producing Gram-negative bacteria, colistin and minocycline can be used as an alternative drug as they have fewer side effects and are more affordable. Minocycline can be used as an alternative to colistin because it is feasible to convert from an injectable to an oral formulation.
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  • 文章类型: Journal Article
    肺炎克雷伯菌的生物膜形成可以保护细菌免受抗生素的侵害,并且难以根除。因此,抗生素亚抑制浓度对细菌的影响变得越来越重要。我们的研究表明,四环素类抗生素的亚最低抑制浓度(亚MIC)可以增加对米诺环素耐药的肺炎克雷伯菌临床菌株的生物膜形成。然而,在细菌粘附和侵袭实验中,粘附性和侵袭能力下降,海绵铁的存活率增加。在四环素抗生素治疗的亚MIC下,扫描电镜观察到细菌的异常拉伸。用四环素的亚MIC处理导致表面疏水性和eDNA含量增加以及外膜渗透性降低。FIMA的表达水平,luxS,qseB,qseC基因减少,mrkA的表达水平升高,不同四环素类抗生素处理下acrA的表达水平不一致。一起,我们的结果表明,四环素类抗生素亚MIC引起的肺炎克雷伯菌生物膜形成的增加可能是通过影响细菌的理化性质和相关基因表达而发生的.
    Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.
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