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Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review. 诊断和治疗 COVID-19 的新方法:非系统综述。
Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2105-45
Şebnem Garip Ustaoğlu, Hakan Kaygusuz, Mehmet Dinçer Bilgin, Feride Severcan

Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.

自 COVID-19 大流行持续升温和蔓延以来,文献中开始出现一些关于 COVID-19 的原创文章和综述文章。这些综述文章主要关注该流行病的现状以及电晕诊断和治疗过程的现状。由于目前使用的方法存在一些弊端,因此改进有前景的新型电晕病毒诊断和治疗方法是非常重要的问题。在这篇综述中,我们在简要讨论了当前诊断和治疗方法的现状之后,向科学界介绍了诊断和治疗 COVID-19 的有前途的新方法。与其他新型方法一样,首先,我们将根据相关文献,讨论质谱和光学光谱方法(如紫外/可见光、红外和拉曼光谱)结合化学计量学对电晕病毒感染样本的诊断潜力。在振动光谱研究中,由于数据的复杂性,也会对数据采用多元分析方法。多变量分析工具可用于从数据中提取有用信息,以达到诊断和表征的目的。审查的方法包括分层聚类分析、主成分分析、线性和二次判别分析、支持向量机算法以及一种神经网络形式,即深度学习方法。其次,将讨论新型治疗方法,如光动力疗法和在电晕内病毒疗法中使用纳米粒子。最后,还将讨论 COVID-19 中有前景的新型诊断和治疗方法相对于标准方法的优势。本文的主要目的之一是鼓励科学界探索这种新型工具在电晕病毒特征描述、诊断和治疗中的应用潜力。
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引用次数: 0
Binary-QSAR guided virtual screening of FDA approved drugs and compounds in clinical investigation against SARS-CoV-2 main protease. 基于二元qsar的FDA批准的抗SARS-CoV-2主要蛋白酶药物和化合物的虚拟筛选
Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2106-61
Lalehan Oktay, Ece Erdemoğlu, İlayda Tolu, Yeşim Yumak, Ayşenur Özcan, Elif Acar, Şehriban Büyükkiliç, Alpsu Olkan, Serdar Durdaği

With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (Mpro). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 Mpro.

随着新型SARS-CoV-2病毒的出现,药物再利用研究变得非常重要。结合最近基于配体和靶标的虚拟筛选方法的改进,虚拟筛选变得比以往任何时候都更快、更高效。在目前的研究中,使用MetaCore/ metdrug平台的抗病毒治疗活性二元QSAR模型筛选FDA批准的临床研究药物和化合物库的抗病毒活性。在6733种化合物中,我们发现370种化合物的标准化治疗活性值大于0.75。只有这些选定的化合物被用于针对SARS-CoV-2主要蛋白酶(Mpro)的分子对接研究。在最初的短时间(10 ns)分子动力学(MD)模拟和分子力学广义出生表面积(MM/GBSA)计算后,前10名化合物进行了更长的(100 ns) MD模拟和终点MM/GBSA估计。我们的虚拟筛选方案产生了头孢呋辛酯,这是第二代头孢菌素类抗生素头孢呋辛的酯前药,是一种用于药物再利用的相当大的分子,可用于对抗SARS-CoV-2 Mpro。
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引用次数: 2
Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial. 槲皮素治疗COVID-19患者:一项前瞻性、单中心、随机对照试验
Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2104-16
Hasan Önal, Bengü Arslan, Nurcan Üçüncü Ergun, Şeyma Topuz, Seda Yilmaz Semerci, Mehmet Eren Kurnaz, Yulet Miray Molu, Mehmet Abdussamet Bozkurt, Nurettin Süner, Ali Kocataş

Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.

针对严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)的新预防和治疗策略的科学研究仍在继续。到目前为止,还没有有效的治疗方法,需要开发一种有效的替代治疗方法。本研究旨在评价槲皮素治疗COVID-19的效果。这是一项单中心、前瞻性随机对照队列研究。在429例至少有一种慢性疾病和中重度呼吸道症状的患者中,比较了常规护理与补充QCB(槲皮素、维生素C、菠萝蛋白酶)。记录患者的人口学特征、体征、化验结果及给药资料。终点是在从研究基线到出院、插管或死亡的整个随访期间继续补充QCB。入院时最常见的主诉是疲劳(62.4%)、咳嗽(61.1%)、厌食(57%)、口渴(53.7%)、呼吸窘迫(51%)和寒战(48.3%)。QCB组CRP和铁蛋白水平下降幅度较大(p值均< 0.05)。QCB组血小板和淋巴细胞计数升高较高(p均< 0.05)。QCB并没有降低随访期间发生事件的风险。调整具有统计学意义的参数,包括肺分期、favipiravir的使用和合并症的存在并没有改变结果。虽然两组之间在事件频率方面没有差异,但QCB组有更晚期的肺部发现。QCB补充剂被证明对实验室恢复有积极作用。虽然在事件频率方面各组之间没有差异,但QCB补充组有更晚期的肺部发现,并且QCB补充被证明对实验室恢复/结果有积极影响。因此,我们得出结论,需要进一步开展涉及不同剂量和血浆水平测量的研究,以揭示QCB的剂量/反应关系和生物利用度,以便更好地了解QCB在治疗SARS CoV-2中的作用。
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引用次数: 21
Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy? 大麻素对SARS-CoV-2的治疗效果是否有证据?
Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2105-73
Ahmet Onay, Abdulselam Ertaş, Veysel Süzerer, İsmail Yener, Mustafa Abdullah Yilmaz, Emine Ayaz-Tilkat, Remzi Ekinci, Nesrin Bozhan, Sevgi Irtegün-Kandemir

To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARS-CoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.

为了对抗冠状病毒及其新变种,迫切需要治疗药物和开发在人类一生中有效的疫苗。内源性大麻素系统(ECS)在微循环、免疫系统和自主神经系统的激活中发挥调节剂的作用,同时控制情绪反应、稳态、运动功能、认知和动机等药理功能。ECS含有内源性大麻素、大麻素受体(CBRs)和调节其生物合成、运输和降解的酶。此外,植物大麻素和模拟内源性大麻素作用的合成大麻素在ECS的调节中也发挥着重要作用。大麻素是大麻(cannabis sativa L.)的主要成分,由于其治疗特性,在健康领域受到了国际关注。最近,由于其抗病毒特性,它们已被测试用于治疗新冠肺炎。事实上,大麻素型化合物,特别是大麻素二醇(CBD),从大麻花的花瓣中发现的腺毛中分离,具有报道的抗病毒特性,被假设是与新冠肺炎疾病合并的SARS-CoV-2的治疗选择。相关文章是根据疫情期间主要发表在Web of Science、Google scholar、PubMed、Crossref和ClinicalTrials.gov数据库中的数据库搜索确定的。这些文章评估了大麻素的治疗潜力、作用机制、ECS在免疫系统中的作用、大麻素在严重急性呼吸系统综合征冠状病毒2型败血症中的影响,特别是如果它们涉及大麻素作为治疗和管理严重急性呼吸系统冠状病毒2型及其新变种的药物的应用。尽管需要考虑使用大麻素控制和治疗病毒性疾病的证据目前尚处于起步阶段,但由于它们在缓解疼痛、改善食欲和改善儿童癫痫方面的作用,特别是在癌症和人类免疫缺陷病毒(艾滋病毒/艾滋病)患者中,它们已经为临床医生提供了机会。除此之外,最新的科学证据强调了它们在治疗冠状病毒感染患者中的用途。简言之,所有已报道的临床前和临床研究都表明,通过大麻素系统,大麻素,特别是CBD,具有许多有效治疗严重急性呼吸系统综合征冠状病毒2型感染患者的机制。因此,有必要在这一领域进行更广泛的研究,以充分确定大麻素对严重急性呼吸系统综合征冠状病毒2型的影响。
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引用次数: 4
Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy. 鉴定正乙酰-L-半胱氨酸和异丙肾上腺素诱导心脏肥大重塑的血清预测因子。
Pub Date : 2021-06-23 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2101-56
Dharaniyambigai Kuberapandian, Victor Arokia Doss

Cardiac hypertrophy (CH), leading to cardiac failure is due to chronic metabolic alterations occurring during cellular stress. Besides the already known relationship between oxidative stress and CH, there are implications of reductive stress leading to CH. This study attempted to develop reductive stress-based CH rat model using n-acetyl-L-cysteine (NAC), a glutathione agonist that was compared with typical isoproterenol (ISO) induced CH model. The main objective was to identify serum metabolites that can serve as potent predictors for seven routine clinical and diagnostic parameters in CH: 3-hydroxybutyrate (3-HB), lactic acid (LA), urea, and ECG-CH parameters (QRS complex, R-amplitude, R-R interval, heart rate) that were hypothesized to underlie metabolic remodelling in this study. CH was assessed using electrocardiography, hypertrophic index and histopathological analysis (H&E stain) in both ventricles after 2 weeks. Gas chromatography mass spectroscopy analysis (GC-MS) identified unique metabolite finger-prints. Correlation and pattern analysis revealed strong relationships between specific metabolites and parameters (Pearson's score > 0.7) of this study. Multiple regression analysis (MRA) for the strongly related metabolites (independent variables) with each of the seven parameters (dependent variables) identified significant predictors for the latter namely fructose, valine, butanoic acid in NAC and cholesterol, erythrose, isoleucine in ISO models, with proline and succinic acid as common for both models. Metabolite set enrichment analysis (MSEA) of those significant predictors (p < 0.05) mapped butyrate metabolism as highly influential pathway in NAC, with arginine-proline metabolism and branched chain amino acid (BCAA) degradation as common pathways in both models, thus providing new insights towards initial metabolic remodeling in the pathogenesis of CH.

心肌肥大(CH)导致心力衰竭的原因是细胞应激过程中发生的慢性代谢改变。除了已知的氧化应激与心肌肥大之间的关系外,还存在还原性应激导致心肌肥大的影响。本研究试图利用谷胱甘肽激动剂 n-乙酰-L-半胱氨酸(NAC)建立基于还原应激的 CH 大鼠模型,并与典型的异丙肾上腺素(ISO)诱导的 CH 模型进行比较。研究的主要目的是确定血清代谢物,这些代谢物可作为慢性心肌梗死的七个常规临床和诊断参数的有效预测因子:3-羟丁酸(3-HB)、乳酸(LA)、尿素和心电图-慢性心肌梗死参数(QRS 波群、R 波幅、R-R 间期、心率),本研究假设这些参数是代谢重塑的基础。2 周后,使用心电图、肥厚指数和组织病理学分析(H&E 染色)对两个心室的 CH 进行评估。气相色谱-质谱分析(GC-MS)确定了独特的代谢物指纹图谱。相关性和模式分析显示,特定代谢物与本研究参数(皮尔逊评分大于 0.7)之间存在密切关系。对与七个参数(因变量)中每个参数密切相关的代谢物(自变量)进行多元回归分析(MRA),确定了后者的重要预测因子,即 NAC 模型中的果糖、缬氨酸和丁酸,以及 ISO 模型中的胆固醇、红糖和异亮氨酸,而脯氨酸和琥珀酸则是这两个模型的共同预测因子。对这些重要预测因子(p < 0.05)进行的代谢物集富集分析(MSEA)显示,丁酸代谢是 NAC 中影响较大的途径,精氨酸-脯氨酸代谢和支链氨基酸(BCAA)降解是两个模型的共同途径,从而为 CH 发病机制中的初始代谢重塑提供了新的见解。
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引用次数: 0
The promising effects of BMP2 transfected mesenchymal stem cells on human osteosarcoma. BMP2转染间充质干细胞治疗人骨肉瘤的前景
Pub Date : 2021-06-23 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2101-50
Ahmet Sinan Sari, Emre Demirçay, Ahmet Öztürk, Ayşen Terzi, Erdal Karaöz

Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with BMP2 to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with BMP2 (BMP2+hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2+hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2+hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process.

选择性靶向转染的间充质干细胞(MSCs)携带特异性抗原基因的肿瘤被认为是一种治疗选择。骨形态发生蛋白-2 (Bone morphogenetic protein-2, BMP2)可抑制骨肉瘤细胞的增殖和侵袭性。在这里,我们的目的是评估腹腔注射转染BMP2的hMSCs到肿瘤部位的归巢效率,以及它们对原位异种移植小鼠模型的OS的影响。采用143B细胞建立6周龄NOD/SCID雌性小鼠原位移植小鼠OS模型。使用转染BMP2的hMSCs (BMP2+hMSC)。体内实验在四组小鼠中进行,这些小鼠不接受治疗,或腹腔注射BMP2、hMSCs和BMP2+hMSCs。采用组织病理学和免疫组织化学研究来评估病理鉴定,评估肿瘤的大小和坏死灶,肺转移灶的特征,以及p27, Ki-67和caspase-3抗体的免疫染色。RT-PCR检测成骨分化标志物BMP2、BMP4、COL1A1、OPN、OCN、PF4。hMSCs组肿瘤尺寸显著高于其余各组(p < 0.01)。BMP2+hMSCs组的转移灶数量明显低于其他组(p < 0.01)。目前的研究结果表明,腹腔内途径可以有效地将hMSCs靶向到肿瘤组织,从而有效地递送BMP2。在本研究中,BMP2转染的hMSCs对人类骨移植和转移的影响有望实现成骨分化和减少转移过程。
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引用次数: 1
Identification of differentially expressed microRNAs in primary esophageal achalasia by next-generation sequencing. 下一代测序鉴定原发性食管贲门失弛缓症中差异表达的微小RNA。
Pub Date : 2021-06-23 DOI: 10.3906/biy-2101-61
Mahin Gholipour, Javad Mikaeli, Seyed Javad Mowla, Mohammad Reza Bakhtiarizadeh, Marie Saghaeian Jazi, Naeme Javid, Narges Fazlollahi, Masoud Khoshnia, Naser Behnampour, Abdolvahab Moradi

Molecular knowledge regarding the primary esophageal achalasia is essential for the early diagnosis and treatment of this neurodegenerative motility disorder. Therefore, there is a need to find the main microRNAs (miRNAs) contributing to the mechanisms of achalasia. This study was conducted to determine some patterns of deregulated miRNAs in achalasia. This case-control study was performed on 52 patients with achalasia and 50 nonachalasia controls. The miRNA expression profiling was conducted on the esophageal tissue samples using the next-generation sequencing (NGS). Differential expression of miRNAs was analyzed by the edgeR software. The selected dysregulated miRNAs were additionally confirmed using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fifteen miRNAs were identified that were significantly altered in the tissues of the patients with achalasia. Among them, three miRNAs including miR-133a-5p, miR-143-3p, and miR-6507-5p were upregulated. Also, six miRNAs including miR-215-5p, miR-216a-5p, miR-216b-5p, miR-217, miR-7641 and miR-194-5p were downregulated significantly. The predicted targets for the dysregulated miRNAs showed significant disease-associated pathways like neuronal cell apoptosis, neuromuscular balance, nerve growth factor signaling, and immune response regulation. Further analysis using qRT-PCR showed significant down-regulation of hsa-miR-217 (p-value = 0.004) in achalasia tissue. Our results may serve as a basis for more future functional studies to investigate the role of candidate miRNAs in the etiology of achalasia and their application in the diagnosis and probably treatment of the disease.

关于原发性食管贲门失弛缓症的分子知识对于这种神经退行性运动障碍的早期诊断和治疗至关重要。因此,有必要找到参与贲门失弛缓症机制的主要微小RNA(miRNA)。本研究旨在确定贲门失弛缓症中miRNA失调的一些模式。本病例对照研究对52例贲门失弛缓症患者和50例非贲门失弛弛缓症对照进行。使用下一代测序(NGS)对食管组织样本进行miRNA表达谱分析。通过edgeR软件分析miRNA的差异表达。使用定量逆转录聚合酶链反应(qRT-PCR)进一步证实所选择的失调miRNA。在贲门失弛缓症患者的组织中发现了15种显著改变的miRNA。其中,三种miRNA上调,包括miR-133a-5p、miR-143-3p和miR-6507-5p。此外,包括miR-215-5p、miR-216a-5p、miR-21 6b-5p、miR-217、miR-7641和miR-194-5p在内的六种miRNA显著下调。失调miRNA的预测靶点显示出显著的疾病相关途径,如神经元细胞凋亡、神经肌肉平衡、神经生长因子信号传导和免疫反应调节。使用qRT-PCR的进一步分析显示,贲门失弛缓症组织中hsa-miR-217显著下调(p值=0.004)。我们的研究结果可能为未来更多的功能研究奠定基础,以研究候选miRNA在贲门失弛缓症病因中的作用及其在疾病诊断和治疗中的应用。
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引用次数: 3
Polyhydroxyalkanoate accumulation in Streptomyces coelicolor affected by SCO7613 gene region. SCO7613基因区对冷色链霉菌聚羟基烷酸积累的影响
Pub Date : 2021-06-23 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2011-16
Zeynep Demir Öksüz, Tuğrul Doruk, Nevin Yağci, Sedef Tunca Gedik

Polyhydroxyalkanoate (PHA) is stored as an important carbon and energy source in bacterial cells. For biomedical applications, gram-positive bacteria can be better sources of PHAs, since they lack outer membrane lipopolysaccharide. Although gram-positive Streptomyces coelicolor A3(2) has been indicated as a high potential PHA producer, pha C gene that encodes the key enzyme PHA synthase in the metabolic pathway is not determined in its genome. BLAST search results of the GenBank database argued that SCO7613 could specify a putative polyhydroxyalkanoate synthase (PhaC) responsible for PHA biosynthesis. Deduced amino acid sequence of SCO7613 showed the presence of conserved lipase box like sequence, 555GASAG559, in which serine residue was present as the active nucleophile. Present study describes deletion of putative S. coelicolor pha C gene via PCR dependent method. We showed that SCO7613 is not an essential gene in S. coelicolor and its deletion affected PHA accumulation negatively although it is not ceased. Transcomplementation abolished the mutant phenotype, demonstrating that the decrease in PHA resulted from the deletion of SCO7613.

聚羟基烷酸酯(PHA)作为一种重要的碳和能量来源储存在细菌细胞中。对于生物医学应用,革兰氏阳性细菌可以作为pha的更好来源,因为它们缺乏外膜脂多糖。虽然革兰氏阳性的coelicolstreptomyces A3(2)已被认为是高潜力的PHA生产者,但在其基因组中尚未确定编码代谢途径中关键酶PHA合成酶的PHA C基因。GenBank数据库的BLAST搜索结果表明,SCO7613可以指定一种假定的PHA生物合成的聚羟基烷酸合成酶(PhaC)。推导出SCO7613的氨基酸序列,发现存在保守的脂肪酶盒状序列555GASAG559,其中丝氨酸残基作为活性亲核试剂存在。本研究通过PCR依赖的方法描述了推测的葡萄球菌pha C基因的缺失。我们发现SCO7613不是葡萄球菌的必需基因,它的缺失虽然没有停止,但对PHA的积累有负面影响。转互补消除了突变表型,表明PHA的减少是由于SCO7613的缺失造成的。
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引用次数: 0
Lipase from new isolate Bacillus cereus ATA179: optimization of production conditions, partial purification, characterization and its potential in the detergent industry. 蜡样芽孢杆菌ATA179脂肪酶:生产条件优化、部分纯化、表征及其在洗涤剂工业中的应用潜力
Pub Date : 2021-06-23 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2101-22
Elif Demirkan, Aynur Aybey Çetinkaya, Maoulida Abdou

In this study, 341 Bacillus sp. strains were isolated from agricultural soils of Turkey. The potent extracellular lipase producer was selected. It was identified by 16S rRNA, named as Bacillus cereus ATA179. Optimal nutritional and physical parameters for lipase production were determined. Sucrose as the carbon source, (NH4)2HPO4 as the nitrogen source, CaCl2 as the metal ion were obtained. The best results of physical parameters were stated at 45°C, pH 7.0, shaking rate 50 rpm, inoculation amount 7% and inoculum age 24 h. ATA179 strain showed a 51% increase in enzyme production in the modified medium created by optimizing nutritional and physical conditions. Optimum pH value and temperature were found as 6.0 and 55 °C, respectively. CaCl2, Tween 20, Triton X-100 had an activating effect on enzyme activity. Vmax and Km kinetic values were found as 18.28 U/mL and 0.11 mM, respectively. The molecular weight was determined as 47 kDa. Lipase was found to be stable up to 75 days at -20 ºC. The potential of the enzyme in detergent industry was also investigated. It was not affected by detergent additives, but was found to be effective in removing oils from contaminated fabrics. This new lipase may have potential to be used in detergent industry.

本研究从土耳其农业土壤中分离得到341株芽孢杆菌。筛选出了胞外脂肪酶产生菌。经16S rRNA鉴定,命名为蜡样芽孢杆菌ATA179。确定了脂肪酶生产的最佳营养和物理参数。以蔗糖为碳源,(NH4)2HPO4为氮源,CaCl2为金属离子。在45°C、pH 7.0、摇速50 rpm、接种量7%、接种时间24 h的条件下,菌株ATA179在优化营养和物理条件后的培养基中酶产量提高51%。最佳pH值为6.0℃,最佳温度为55℃。CaCl2、Tween 20、Triton X-100对酶活性有激活作用。Vmax和Km动力学值分别为18.28 U/mL和0.11 mM。分子量测定为47 kDa。脂肪酶在-20℃下稳定75天。探讨了该酶在洗涤剂工业中的应用潜力。它不受洗涤剂添加剂的影响,但被发现可以有效地去除受污染织物上的油。这种新型脂肪酶在洗涤剂工业中具有潜在的应用前景。
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引用次数: 3
Transcriptome profiling of Stevia rebaudiana MS007 revealed genes involved in flower development. 甜菊糖MS007转录组分析揭示了与花发育有关的基因。
Pub Date : 2021-06-23 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2103-3
Nurul Hidayah Samsulrizal, Khairul Shahyidi Khadzran, Tamil Chelvan Meenakshi Sundram, Zarina Zainuddin, Siti Hajar Nor Shaarani, Nur Sabrina Ahmad Azmi, Sarahani Harun

Stevia rebaudiana is a medicinal plant recommended to diabetic or obese patients as an alternative sweetener owing to its low-calorie property. Previous studies have found that the stevioside level is highest at the time of flower bud formation and lowest at the time of preceding and following flower bud formation. Hence, this study aims to identify the genes involved in the flowering of local S. rebaudiana accession MS007 by investigating the transcriptomic data of two stages of growth, before flowering (BF) and after flowering (AF) that were deposited under accession number SRX6362785 and SRX6362784 at the NCBI SRA database. The transcriptomic study managed to annotate 108299 unigenes of S. rebaudiana with 8871 and 9832 genes that were differentially expressed in BF and AF samples, respectively. These genes involved in various metabolic pathways related to flower development, response to stimulus as well as photosynthesis. Pheophorbide A oxygenase ( PAO ), eukaryotic translation initiation factor 3 subunit E ( TIF3E1 ), and jasmonate ZIM domain-containing protein 1 ( JAZ1 ) were found to be involved in the flower development. The outcome of this study will help further research in the manipulation of the flowering process, especially in the breeding programme to develop photo-insensitive Stevia plant.

甜菊糖是一种药用植物,由于其低热量的特性,被推荐给糖尿病或肥胖患者作为替代甜味剂。以往的研究发现,甜菊苷含量在花芽形成时最高,在花芽形成前后最低。因此,本研究旨在通过对NCBI SRA数据库中登记号SRX6362785和SRX6362784下的开花前(BF)和开花后(AF)两个生长阶段的转录组学数据进行研究,以确定与本地梨属植物MS007开花相关的基因。转录组学研究成功地用8871和9832个在BF和AF样品中差异表达的基因分别注释了S. reaudiana的108299个unique genes。这些基因参与了与花发育、对刺激的反应以及光合作用有关的各种代谢途径。研究发现,叶绿素A加氧酶(PAO)、真核翻译起始因子3亚基E (TIF3E1)和茉莉酸ZIM结构域含蛋白1 (JAZ1)参与了花的发育。本研究结果将有助于进一步研究甜叶菊开花过程的调控,特别是培育光不敏感甜叶菊的育种计划。
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引用次数: 1
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Turkish journal of biology = Turk biyoloji dergisi
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