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Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study 非典型抗精神病药物稳定的精神分裂症患者服用α -硫辛酸的代谢和临床效果:一项为期12周的开放对照研究
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100116
Fiammetta Iannuzzo , Gianpaolo Antonio Basile , Domenica Campolo , Giovanni Genovese , Gianluca Pandolfo , Loretta Giunta , Domenica Ruggeri , Antonino Di Benedetto , Antonio Bruno

Background

Many of the atypical antipsychotics induce metabolic side effects, limiting their use in clinical practice. Alpha-lipoic acid (ALA) was proposed as a new approach in schizophrenia to improve metabolic effects of atypical antipsychotics. The aim of the study is to evaluate the effect of ALA on metabolic and clinical parameters among schizophrenic subjects.

Methods

15 schizophrenic subjects, in stable atypical antipsychotic monotherapy were included in the study. ALA was administrated at the oral daily dose of 600 ​mg/d in addition to antipsychotic therapy. Metabolic, clinical, and psychopathological parameters were measured at typical antipsychotics. e initial screening, and after 12 weeks.

Results

ALA produced a statistically significant reduction in QTc (p ​= ​0.012), blood glucose (p ​= 0.005), AST (p ​= ​0.021), γGT (p ​= ​0.035), CPK (p ​= ​0.005) and prolactinaemia (p ​= ​0.026). In contrast, there was a significant increase in HbA1c (p ​= ​0.026). No effects on body weight and blood lipid levels (triglycerides, total cholesterol, HDL, LDL) emerged.

Conclusions

ALA treatment appeared to be effective for reducing diabetes risk, liver functionality parameters, hyperprolactinaemia and QTC interval. ALA appears to be safe as adjunctive components in schizophrenia.

背景:许多非典型抗精神病药物引起代谢副作用,限制了它们在临床实践中的应用。α -硫辛酸(ALA)被认为是改善非典型抗精神病药物代谢作用的新途径。本研究的目的是评估ALA对精神分裂症患者代谢和临床参数的影响。方法选取稳定非典型抗精神病药单药治疗的精神分裂症患者15例。除抗精神病治疗外,ALA每日口服剂量为600 mg/d。在典型抗精神病药物组测量代谢、临床和精神病理参数。E初始筛查,12周后。结果sala降低QTc (p = 0.012)、血糖(p = 0.005)、AST (p = 0.021)、γ - gt (p = 0.035)、CPK (p = 0.005)、催乳素血症(p = 0.026)均有统计学意义。相比之下,HbA1c显著升高(p = 0.026)。对体重和血脂水平(甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白)没有影响。结论sala治疗对降低糖尿病风险、肝功能指标、高泌乳素血症和QTC间期均有显著疗效。ALA作为精神分裂症的辅助成分似乎是安全的。
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引用次数: 2
When disease extent is not always a key parameter: Management of refractory ulcerative proctitis 当疾病程度不总是一个关键参数:难治性溃疡性直肠炎的处理
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2021.100071
Georgios Michalopoulos , Konstantinos Karmiris

Background

Patients with ulcerative proctitis represent a sub-group of ulcerative colitis patients with specific characteristics. Disease-related symptoms, endoscopic findings and patient's personality perspectives create a difficult-to-assess condition in certain cases.

Objectives

To summarize available evidence on the management of refractory ulcerative proctitis and provide insights in treatment options.

Results

/Conclusion: Topical therapy plays a central role due to the location of the disease. However, well-established treatment options may become exhausted in a considerable proportion of ulcerative proctitis patients, indicating the need to advance to more potent therapies in order to induce and maintain clinical response and remission in these refractory cases. Systemic corticosteroids, thiopurines, calcineurin inhibitors, biologic agents and small molecules have all been tested with variable success rates. Investigational interventions as well as surgical procedures are kept as the ultimate resort in multi-treatment resistant cases. Identifying early prognostic factors that herald a disabling disease progression will help in optimizing treatment and avoiding surgery.

背景溃疡性直肠炎患者是溃疡性结肠炎患者的一个亚组,具有特定的特征。在某些情况下,疾病相关症状、内窥镜检查结果和患者的个性观点造成了难以评估的状况。目的总结难治性溃疡性直肠炎治疗的现有证据,为治疗方案提供参考。结果/结论:局部治疗因其病变部位而起核心作用。然而,在相当一部分溃疡性直肠炎患者中,完善的治疗方案可能会耗尽,这表明需要推进更有效的治疗,以诱导和维持这些难治性病例的临床反应和缓解。全身皮质类固醇、硫嘌呤、钙调磷酸酶抑制剂、生物制剂和小分子药物都进行了测试,成功率各不相同。调查干预和外科手术仍然是多重治疗耐药病例的最终手段。识别预示致残疾病进展的早期预后因素将有助于优化治疗和避免手术。
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引用次数: 1
Examination of central nervous system by functional observation battery after massive intravenous infusion of carbon monoxide-bound and oxygen-bound hemoglobin vesicles in rats 大鼠大量静脉输注一氧化碳和氧结合血红蛋白囊泡后中枢神经系统功能观察电池的观察
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100135
Hiromi Sakai , Shunichi Yasuda , Chie Okuda , Tetsuya Yamada , Keita Owaki , Yoji Miwa

Carbon monoxide (CO) is known as a toxic gas inducing “CO poisoning”, which acutely affects the central nervous system (CNS) and which persistently affects brain functions depending on the exposure time and CO concentration. By contrast, in pathological rodent models, intravenous infusion of CO-bound hemoglobin vesicles (CO-HbV) has shown various beneficial effects such as anti-oxidative and anti-inflammatory reactions. This study assessed effects of CO-HbV infusion on CNS using a functional observation battery, sensory reflexes, grip strength, and landing foot splay measurements. The test fluids were CO-HbV and O2-bound HbV (O2-HbV) suspended in saline ([Hb] ​= ​10 ​g/dL), and saline alone for comparison. The rats received either 16 or 32 ​mL/kg of fluid intravenously at 1.5 ​mL/min/kg. Observations were made before infusion, and at 5 ​min, 4, 8, 24, 48 and 72 ​h after infusion. Massive doses of 16 and 32 ​mL/kg respectively corresponded to about 29 and 57% of the whole circulating blood volume (56 ​mL/kg). No toxicological effect was observed in any measurement item for any group in comparison to the control saline infusion group. Histopathological examination of hippocampal tissue at 14 days after infusion showed the number of necrotic cells to be minimal. Results obtained from rats in this experiment suggest that the massive intravenous infusion of CO-HbV yields beneficial anti-oxidative and anti-inflammatory effects without showing CO-poisoning-related symptoms of CNS damage.

一氧化碳(CO)是一种引起“一氧化碳中毒”的有毒气体,它会严重影响中枢神经系统(CNS),并根据暴露时间和CO浓度持续影响大脑功能。相比之下,在病理啮齿类动物模型中,静脉输注co结合血红蛋白囊泡(CO-HbV)显示出抗氧化和抗炎反应等多种有益作用。本研究通过功能观察电池、感觉反射、握力和落地脚张开测量来评估CO-HbV输注对中枢神经系统的影响。试验液体为CO-HbV和o2结合的HbV (O2-HbV)悬浮在生理盐水中([Hb] = 10 g/dL),和单独生理盐水进行比较。大鼠以1.5 mL/min/kg的速度静脉注射16或32 mL/kg的液体。分别于注射前、注射后5 min、4、8、24、48、72 h进行观察。大剂量剂量分别为16和32 mL/kg,约占全循环血容量(56 mL/kg)的29%和57%。与生理盐水对照组相比,各组各测量项目均未见毒理学效应。注射后第14天海马组织病理检查显示坏死细胞数量极少。本实验大鼠实验结果表明,大量静脉输注CO-HbV可产生有益的抗氧化和抗炎作用,而不会出现CO-HbV中毒相关的中枢神经系统损伤症状。
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引用次数: 2
Plant metabolite diosmin as the therapeutic agent in human diseases 植物代谢物薯蓣皂苷作为人类疾病的治疗剂
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100122
Saad Mustafa , Mahmood Akbar , Mohammad Aasif Khan , Kumari Sunita , Shabana Parveen , Jogendra Singh Pawar , Sheersh Massey , Nupur Rani Agarwal , Syed Akhtar Husain

Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.

植物源性黄酮类化合物近年来一直是研究的热点,主要是近十年来由于其治疗特性。迄今为止,已从植物中鉴定出约4000种黄酮类化合物,薯蓣皂苷(一种黄酮类苷)就是其中之一。在线数据库、先前的研究和综述已被用于收集薯蓣皂苷的抗氧化、免疫调节、抗癌、抗寄生虫和抗微生物特性的信息。综述了薯蓣皂苷与其他类黄酮的联用作用,并对其给药途径进行了综述。此外,我们还研究了薯蓣皂苷对关键蛋白质网络的影响。它对糖尿病及其相关并发症如神经病变和血脂异常有治疗作用。地奥司明与橙皮苷联合治疗慢性静脉功能不全和痔疮是非常有效的。薯蓣皂苷是一种精美的治疗剂单独以及与其他类黄酮的组合。
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引用次数: 10
Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases mirna在心血管疾病相关Wnt信号通路中的调节作用
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100133
Jiban Kumar Behera , Manojit Bhattacharya , Pabitra Mishra , Akansha Mishra , Adya Anindita Dash , Niladri Bhusan Kar , Bhaskar Behera , Bidhan Chandra Patra

MicroRNAs (miRNAs) are discovered in science about 23 years ago. These are short, a series of non-coding, single-stranded and evolutionary conserved RNA molecules found in eukaryotic cells. It involved post-transcriptional fine-tune protein expression and repressing the target of mRNA in different biological processes. These miRNAs binds with the 3′-UTR region of specific mRNAs to phosphorylate the mRNA degradation and inhibit the translation process in various tissues. Therefore, aberrant expression in miRNAs induces numerous cardiovascular diseases and developmental defects. Subsequently, the miRNAs and Wnt singling pathway are regulating a cellular process in cardiac development and regeneration, maintain the homeostasis and associated heart diseases. In Wnt signaling pathway majority of the signaling components are expressed and regulated by miRNAs, whereas the inhibition or dysfunction of the Wnt signaling pathway induces cardiovascular diseases. Moreover, inadequate studies about the important role of miRNAs in heart development and diseases through Wnt signaling pathway has been exist still now. For this reason in present review we summarize and update the involvement of miRNAs and the role of Wnt signaling in cardiovascular diseases. We have discussed the mechanism of miRNA functions which regulates the Wnt components in cellular signaling pathway. The fundamental understanding of Wnt signaling regulation and mechanisms of miRNAs is quite essential for study of heart development and related diseases. This approach definitely enlighten the future research to provide a new strategy for formulation of novel therapeutic approaches against cardiovascular diseases.

MicroRNAs (miRNAs)是在大约23年前被科学发现的。这些是真核细胞中发现的一系列短的、非编码的、单链的、进化保守的RNA分子。它涉及转录后微调蛋白表达和抑制mRNA在不同生物过程中的靶标。这些mirna与特定mRNA的3 ' -UTR区结合,使mRNA降解磷酸化,抑制各种组织的翻译过程。因此,miRNAs的异常表达诱导了许多心血管疾病和发育缺陷。随后,mirna和Wnt单链通路调节心脏发育和再生的细胞过程,维持体内平衡和相关心脏病。在Wnt信号通路中,大部分信号组分由mirna表达和调控,而Wnt信号通路的抑制或功能障碍可诱发心血管疾病。此外,目前关于mirna通过Wnt信号通路在心脏发育和疾病中的重要作用的研究仍然不足。因此,在本综述中,我们总结和更新了mirna的参与和Wnt信号在心血管疾病中的作用。我们讨论了miRNA在细胞信号通路中调控Wnt组分的作用机制。了解Wnt信号调控及mirna的作用机制对心脏发育及相关疾病的研究至关重要。该方法对今后的研究具有一定的启发意义,为制定心血管疾病的新治疗方法提供了新的策略。
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引用次数: 0
miRNA nanoencapsulation to regulate the programming of the blood-brain barrier permeability by hypoxia miRNA纳米包封调节缺氧对血脑屏障通透性的编程
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100129
Esteban G. Figueroa , Aitor Caballero-Román , Josep R. Ticó , Montserrat Miñarro , Anna Nardi-Ricart , Alejandro González-Candia

Central nervous system (CNS)-related diseases are difficult to treat as most therapeutic agents they cannot reach the brain tissue, mainly due to the blood-brain barrier (BBB), arguably the tightest barrier between the human body and cerebral parenchyma, which routinely excludes most xenobiotic therapeutics compounds. The BBB is a multicellular complex that structurally forms the neurovascular unit (NVU) and is organized by neuro-endothelial and glial cells. BBB breakdown and dysfunction from the cerebrovascular cells lead to leakages of systemic components from the blood into the CNS, contributing to neurological deficits. Understanding the molecular mechanisms that regulate BBB permeability and disruption is essential for establishing future therapeutic strategies to restore permeability and improve cerebrovascular health. MicroRNAs (miRNAs), a type of small non-coding RNAs, are emerging as an important regulator of BBB integrity by modulating gene expression by targeting mRNA transcripts. miRNAs is implicated in the development and progression of various illnesses. Conversely, nanoparticle carriers offer unprecedented opportunities for cell-specific controlled delivery of miRNAs for therapeutic purposes. In this sense, we present in this graphical review critical evidence in the regulation of cell junction expression mediated by miRNAs induced by hypoxia and for the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of BBB permeability.

中枢神经系统(CNS)相关疾病很难治疗,因为大多数治疗药物无法到达脑组织,这主要是由于血脑屏障(BBB),可以说是人体和脑实质之间最紧密的屏障,通常排除了大多数外源治疗化合物。血脑屏障是一种多细胞复合物,在结构上形成神经血管单位(NVU),由神经内皮细胞和神经胶质细胞组织。血脑屏障的破坏和脑血管细胞的功能障碍导致血液中的系统成分渗漏到中枢神经系统,导致神经功能障碍。了解调节血脑屏障通透性和破坏的分子机制对于建立未来恢复通透性和改善脑血管健康的治疗策略至关重要。MicroRNAs (miRNAs)是一种小的非编码rna,通过靶向mRNA转录物调节基因表达,成为血脑屏障完整性的重要调节剂。mirna与各种疾病的发生和发展有关。相反,纳米颗粒载体为治疗目的的细胞特异性控制递送mirna提供了前所未有的机会。从这个意义上说,我们在这篇图表综述中提出了缺氧诱导的mirna介导的细胞连接表达调节的关键证据,以及使用纳米颗粒递送基于mirna的治疗方法来治疗血脑屏障通透性。
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引用次数: 2
Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications emoxypine及其琥珀酸盐衍生物在各种疾病治疗中的有希望的作用-对最近专利申请的见解
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100121
Dhruv Sanjay Gupta, Siddhi Bagwe Parab, Ginpreet Kaur

Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.

艾莫西平及其琥珀酸衍生物具有与吡哆醇相似的羟基吡啶结构。由于具有广泛的特性,这些化合物已被用于治疗和工业上。这包括抗缺氧,神经保护和心脏保护作用,以及药代动力学方面的好处,如通过血脑屏障(BBB)的能力,由于其相对较小的尺寸和低分子量。据观察,emoxypine在体外表现出铁螯合特性,表明其在治疗神经退行性疾病(如阿尔茨海默病(AD))以及血液系统疾病(如地中海贫血和血色素沉着症)方面的应用前景良好。除此之外,它还被观察到具有强大的抗氧化作用,因此,它可能被认为可以改善自由基损伤引起的疾病。对其作用机制及其在细胞和分子水平上的意义的研究将有助于进一步了解其益处,以及申请新专利的前景。本综述的主要重点是阐明emoxypine及其琥珀酸衍生物提供的广泛药理学特性,并强调增加临床前和临床试验的范围,以评估其安全性和有效性。除此之外,本文的重点还包括这些药物最近申请的专利和新应用的范围。
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引用次数: 6
Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state 脯氨酰羟化酶抑制剂去西杜司他改善红细胞生成素低反应状态下的贫血
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100102
Amit A. Joharapurkar, Vishal J. Patel, Samadhan G. Kshirsagar, Maulik S. Patel, Hardikkumar H. Savsani, Chetan Kajavadara, Darshan Valani, Mukul R. Jain

Many anemic chronic kidney disease (CKD) patients are refractory to erythropoietin (EPO) effects due to inflammation, deranged iron utilization, and generation of EPO antibodies. This work assessed the effect of desidustat, an inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase (PHD), on EPO-refractory renal anemia. Sprague Dawley rats were made anemic by cisplatin (5 ​mg/kg, IP, single dose) and turpentine oil (5 ​mL/kg, SC, once a week). These rats were given recombinant human EPO (rhEPO, 1 ​μg/kg) and desidustat (15 or 30 ​mg/kg) for eight weeks. Separately, rhEPO (1–5 ​μg/kg) was given to anemic rats to sustain the normal hemoglobin levels and desidustat (15 ​mg/kg) for eight weeks. In another experiment, the anemic rats were treated rhEPO (5 ​μg/kg) for two weeks and then desidustat (15 ​mg/kg) for the next two weeks. Dosing of rhEPO was thrice a week, and for desidustat, it was on alternate days. Desidustat inhibited EPO-resistance caused by rhEPO treatment, decreased hepcidin, IL-6, IL-1β, and increased iron and liver ferroportin. Desidustat reduced EPO requirement and anti-EPO antibodies. Desidustat also maintained normal hemoglobin levels after cessation of rhEPO treatment. Thus, novel prolyl hydroxylase inhibitor desidustat can treat EPO resistance via improved iron utilization and decreased inflammation.

许多贫血性慢性肾脏疾病(CKD)患者由于炎症、铁利用紊乱和EPO抗体的产生而对促红细胞生成素(EPO)的作用难治性。本研究评估了缺氧诱导因子(HIF)脯酰羟化酶(PHD)抑制剂德西杜司他对epo难治性肾性贫血的作用。用顺铂(5mg /kg,单次给药)和松节油(5ml /kg,单次给药,每周1次)致sd大鼠贫血。给予重组人促红细胞生成素(rhEPO, 1 μg/kg)和去西杜司他(15或30 mg/kg) 8周。分别给予贫血大鼠rhEPO (1-5 μg/kg)和去西杜司他(15 mg/kg)维持血红蛋白正常水平8周。在另一个实验中,贫血大鼠先给予rhEPO (5 μg/kg)治疗2周,再给予去西杜司他(15 mg/kg)治疗2周。rhEPO每周给药3次,desidustat隔天给药。去西杜司他抑制rhEPO处理引起的epo耐药,降低hepcidin、IL-6、IL-1β,增加铁和肝铁转运蛋白。Desidustat降低EPO需求和抗EPO抗体。停用rhEPO治疗后,Desidustat也能维持正常的血红蛋白水平。因此,新型脯氨酰羟化酶抑制剂去西杜司他可以通过改善铁利用率和减少炎症来治疗EPO抵抗。
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引用次数: 2
Myrtenal mitigates streptozotocin-induced spatial memory deficit via improving oxido inflammatory, cholinergic and neurotransmitter functions in mice 桃金娘醛通过改善小鼠氧化炎症、胆碱能和神经递质功能减轻链脲佐菌素诱导的空间记忆缺陷
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100106
Isaac Oluwatobi Akefe , Victoria Aderonke Adegoke , Ibrahim Yusuf Lamidi , Matthew Phillip Ameh , Enokela Shaibu Idoga , Simon Azubuike Ubah , Itopa Etudaye Ajayi

The occurrence of chronic neurodegenerative disorders is on the rise, but with no effective treatment due to the paucity of information on the pathological mechanism underlying these disorders. Thus, this study investigated the role of oral administration of myrtenal in mitigating memory deficits and neuro-biochemical alterations in streptozotocin-demented mice model. Mice (n ​= ​35) were randomly allocated into five cohorts consisting of 7 mice each; Group I: Control mice received vehicle alone; Group II: streptozotocin; Group III: streptozotocin + 100 ​mg/kg myrtenal; Group IV: streptozotocin +200 ​mg/kg myrtenal; and Group V: streptozotocin ​+ ​donepezil 0.5 ​mg/kg. Data from this study demonstrated that the administration of streptozotocin (STZ) impaired spatial memory and induced alterations in markers of oxido-inflammatory response, cholinergic function, cytoarchitecture, and neurotransmitter levels in mice hippocampus. Notably, administration of myrtenal enhanced spatial memory performance in STZ-demented mice by improving the activities of endogenous antioxidant enzymes to protect the brain from oxido-inflammatory stress. Treatment with myrtenal also restored cholinergic function and stabilized the homeostasis of neurotransmitters in STZ-demented mice. The authors infer that fruits rich in myrtenal may be beneficial for treating patients living with dementia associated with Alzheimer's disease.

慢性神经退行性疾病的发病率正在上升,但由于缺乏这些疾病的病理机制的信息,没有有效的治疗。因此,本研究探讨了口服桃金娘酸对减轻链脲佐菌素痴呆小鼠模型的记忆缺陷和神经生化改变的作用。将35只小鼠随机分为5组,每组7只;第一组:对照组小鼠单独给药;第二组:链脲佐菌素;第三组:链脲佐菌素+桃金娘醛100 mg/kg;IV组:链脲佐菌素+桃金娘醛200 mg/kg;V组:链脲佐菌素+多奈哌齐0.5 mg/kg。本研究的数据表明,链脲佐菌素(STZ)的使用损害了小鼠的空间记忆,并诱导了小鼠海马氧化炎症反应、胆碱能功能、细胞结构和神经递质水平的改变。值得注意的是,桃金娘酸通过提高内源性抗氧化酶的活性来保护大脑免受氧化炎症应激,从而增强了stz痴呆小鼠的空间记忆表现。用桃金酸酯治疗也能恢复stz痴呆小鼠的胆碱能功能,稳定神经递质稳态。作者推断,富含桃金娘酸的水果可能对治疗与阿尔茨海默病相关的痴呆症患者有益。
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引用次数: 3
Managing complex perianal disease after anti-TNF failure: Where to go next? 抗肿瘤坏死因子失败后复杂肛周疾病的处理:下一步该何去何从?
Q2 Agricultural and Biological Sciences Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100081
Clare Yzet , Franck Brazier , Charles Sabbagh , Mathurin Fumery

Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.

克罗恩病是一种慢性炎症性肠病,可累及各个肠段,并可累及肛周区域。尽管抗肿瘤坏死因子(TNF)药物已经彻底改变了克罗恩病的治疗方法,改善了肛周克罗恩病(pCD)患者的预后,但其长期疗效有限:超过60%的患者在维持治疗一年后复发。近年来,在抗肿瘤坏死因子失败后治疗复杂肛周瘘管方面取得了重大进展。同时使用抗生素和免疫抑制剂可提高抗肿瘤坏死因子的有效性。治疗药物监测和剂量调整抗肿瘤坏死因子治疗(靶向更高的谷水平)也可能改善治疗反应。新的治疗策略可能为pCD的治疗提供新的机会;例如,ustekinumab可能在抗tnf治疗失败后有效,尽管需要更多的研究。根据最近的国际指南,间充质干细胞注射可能是一种有效、安全的治疗复杂pCD的方法。
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Current Research in Pharmacology and Drug Discovery
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