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Induction of defence response in peanut elicited by Bacillus sp. CHEP5: A biological strategy for control of smut disease caused by Thecaphora frezzii in the field. CHEP5芽孢杆菌诱导花生的防御反应:田间控制由Thecaphora frezzii引起的烟粉病的生物策略。
IF 2.1 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
M S Figueredo, M Kearney, M Zuza, U Loser, A Rago, A Fabra, M L Tonelli

Peanut is susceptible to many diseases; among them, peanut smut disease caused by Thecaphora frezzii is the most damaging, causing yield losses of 30%. Fungicide treatment is not effective to control this disease. In this scenario, biological control would be an alternative to diminish the disease. Systemic resistance induced by a biotic agent is known to be effective against a broad spectrum of pathogens. In this study we evaluated the effect of different inoculation strategies of Bacillus sp. CHEP5, a peanut native strain, on peanut smut incidence and severity in field experiments. Peroxidase activity and accumulation of phenolic compounds were measured as changes associated with induced defensive traits. After three consecutive field trials, we found that Bacillus sp. CHEP5 inoculation protects peanut from T. frezzii because incidence and severity were reduced in two field trials. Furthermore, bacterial inoculation in the furrow followed by foliar application around the date of peg development would be the best strategy to control the disease. In addition, a correlation was found between increase in plant phenolic content and decrease in smut disease parameters. Thereafter, we concluded that Bacillus sp. CHEP5 may reduce smut as a result of plant defence response induction.

花生易感染多种病害,其中由 Thecaphora frezzii 引起的花生烟粉病危害最大,可造成 30% 的减产。杀真菌剂不能有效控制这种病害。在这种情况下,生物防治将是减少这种病害的替代方法。众所周知,生物制剂诱导的系统抗性对多种病原体都有效。在本研究中,我们在田间试验中评估了花生本地菌株芽孢杆菌 CHEP5 的不同接种策略对花生烟粉虱发病率和严重程度的影响。过氧化物酶活性和酚类化合物的积累被测定为与诱导防御性状相关的变化。经过连续三次田间试验,我们发现接种 CHEP5 芽孢杆菌能保护花生免受 T. frezzii 的侵害,因为在两次田间试验中,发病率和严重程度都有所降低。此外,在垄沟中进行细菌接种,然后在花生蕾期前后进行叶面喷施是控制该病害的最佳策略。此外,我们还发现植物酚含量的增加与烟粉虱病害参数的降低之间存在相关性。因此,我们得出结论,CHEP5 芽孢杆菌可通过诱导植物防御反应来减少烟粉虱。
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引用次数: 0
Identification and investigation of barley powdery mildew (Blumeria graminis f. sp. tritici) infection in winter wheat with conventional stress reactions and non-invasive biophoton emission parameters. 利用常规胁迫反应和无创生物光子发射参数识别和调查冬小麦白粉病(Blumeria graminis f. sp.
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Ildikó Jócsák, Helga Lukács, Éva Varga-Visi, Katalin Somfalvi-Tóth, Sándor Keszthelyi

The objective of this study was to characterize the effects of barley powdery mildew infection on wheat via the evolution and dynamics of chloroplasts and oxidative processes based on in vivo measurements of ultra-weak photon emission, parallel measurement of chlorophyll and ascorbic acid content, and molecular identification of the pathogen. The results showed the temporal dynamics of the evolution of ultra-weak photon emission signals that were evidently different for healthy and powdery mildew-infested wheat leaves. In the dark, the ceasing of delayed fluorescence signal made it possible to visualize the ultra-weak luminescence signal as well. Both delayed fluorescence and ultra-weak luminescence signals were characteristic of stress symptoms induced by powdery mildew that was further strengthened by the changes of chlorophyll and ascorbic acid content as typical stress analytical parameters. The presented data and parameterization enabled the identification of stress induction due to powdery mildew infestation in wheat, which should be investigated in detail in the future for fine-tuning our measurements, even by using other species and increasing the length of the measurement in order to increase its specificity. The changes in R2 values are suitable for monitoring the changes of plant stress response. The measurement of fluorescence and luminescence leads to a greater comprehension of the underlying photon emission-related processes, both in general and in the case of powdery mildew infestation.

本研究的目的是根据超弱光子发射的活体测量、叶绿素和抗坏血酸含量的平行测定以及病原体的分子鉴定,通过叶绿体和氧化过程的演变和动态来描述大麦白粉病感染对小麦的影响。结果显示,超弱光子发射信号的时间动态演变在健康小麦叶片和受白粉病侵染小麦叶片上明显不同。在黑暗中,延迟荧光信号停止后,超弱发光信号也可以被观察到。延迟荧光信号和超弱发光信号都是白粉病诱导的胁迫症状的特征,而叶绿素和抗坏血酸含量的变化(典型的胁迫分析参数)进一步加强了这一特征。所提供的数据和参数使我们能够识别小麦白粉病引起的应激诱导,今后应对此进行详细研究,以便对我们的测量进行微调,甚至可以使用其他物种和增加测量长度,以提高其特异性。R2 值的变化适用于监测植物胁迫反应的变化。荧光和发光的测量有助于更好地理解与光子发射相关的基本过程,无论是在一般情况下还是在白粉病侵染的情况下。
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引用次数: 0
Involvement of oxidative stress in localization of bacterial spot infection in pepper plants. 氧化应激参与辣椒植株细菌斑点病感染的定位。
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Liliana Brankova, Elena Shopova, Sergei Ivanov, Yoana Kizheva, Zoltan Urshev, Iliyana Rasheva, Vladimir Aleksandrov, Lyudmila Dimitrova, Melani Dimitrova, Petya Hristova

Xanthomonas euvesicatoria is a major cause of bacterial spot disease in various crops. The present study was focused on the pathosystem pepper (Capsicum annuum L.) - X. euvesicatoria 269p (wild strain). The infectious process was studied using several different modes of in vivo inoculation under controlled conditions. The spread of the pathogen in different parts of the plants was monitored by a new qPCR procedure developed for the detection of X. euvesicatoria, as well as by re-isolation of viable bacterial cells. Photosynthesis, the number of viable pathogens, oxidative stress markers, activities of the main antioxidant enzymes, and levels of nonenzymatic antioxidants in the novel single-leaf model system were studied. The most important observation is that the invasion of the pathogen causes local infection and the dissemination of bacteria to the healthy parts of the host is blocked. The plants limit bacterial colonization around the entry points. Oxidative burst and alterations in antioxidant defenses are detected in infectious leaf lesions. Localized ROS overproduction resembles a hypersensitive response, but several differences can be observed. We assumed that pepper plants are more likely to manifest an intermediate phenotype, similar to lesions simulating disease or leaf flecking. By localizing the infection, possibly involving oxidative stress, the plant survives. However, the same applies to bacteria. The pathogen multiplies at the infection spots and is transmitted to other plants. Our conclusion is that the intermediate phenotype in the studied pathosystem is an example of long and successful co-evolution for both species.

黄单胞菌(Xanthomonas euvesicatoria)是多种作物细菌性斑点病的主要病原菌。本研究的重点是病原系统辣椒(Capsicum annuum L.)--X. euvesicatoria 269p(野生菌株)。在受控条件下,使用几种不同的体内接种模式对感染过程进行了研究。通过为检测 X. euvesicatoria 而开发的新 qPCR 程序以及重新分离有活力的细菌细胞,监测了病原体在植物不同部位的传播情况。研究了新型单叶模型系统中的光合作用、存活病原体的数量、氧化应激标记、主要抗氧化酶的活性和非酶抗氧化剂的水平。最重要的观察结果是,病原体的入侵会造成局部感染,细菌向宿主健康部位的传播受到阻碍。植物限制了细菌在进入点周围的定植。在感染性叶片病变中检测到氧化猝灭和抗氧化防御系统的改变。局部 ROS 过度产生类似于超敏反应,但也能观察到一些不同之处。我们假设辣椒植株更有可能表现出一种中间表型,类似于病害或叶片斑点。通过定位感染(可能涉及氧化应激),植物可以存活下来。然而,细菌也是如此。病原体在感染点繁殖,并传播给其他植物。我们的结论是,所研究的病理系统中的中间表型是两个物种长期共同进化的成功范例。
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引用次数: 0
Non-viral delivery of nucleic acid for treatment of rare diseases of the muscle. 用于治疗罕见肌肉疾病的非病毒性核酸递送。
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Divya Rao, Munia Ganguli

Rare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy (SMA), limb girdle muscular dystrophy, and so on. Due to the infrequent occurrence of these disorders, development of therapeutic approaches elicits less attention compared with other more prevalent diseases. However, in recent times, improved understanding of pathogenesis has led to greater advances in developing therapeutic options to treat such diseases. Exon skipping, gene augmentation, and gene editing have taken the spotlight in drug development for rare neuromuscular disorders. The recent innovation in targeting and repairing mutations with the advent of CRISPR technology has in fact opened new possibilities in the development of gene therapy approaches for these disorders. Although these treatments show satisfactory therapeutic effects, the susceptibility to degradation, instability, and toxicity limits their application. So, an appropriate delivery vector is required for the delivery of these cargoes. Viral vectors are considered potential delivery systems for gene therapy; however, the associated concurrent immunogenic response and other limitations have paved the way for the applications of other non-viral systems like lipids, polymers, cellpenetrating peptides (CPPs), and other organic and inorganic materials. This review will focus on non-viral vectors for the delivery of therapeutic cargoes in order to treat muscular dystrophies.

罕见肌肉疾病(RMDs)是指影响一小部分人群的疾病。这些疾病由基因突变引起,通常表现为骨骼肌和心肌的进行性无力和萎缩。RMDs 包括杜兴氏肌肉萎缩症(DMD)、GNE 肌病、脊髓性肌肉萎缩症(SMA)、肢束性肌肉萎缩症等疾病。由于这些疾病很少发生,与其他更常见的疾病相比,治疗方法的开发较少受到关注。然而,近来人们对发病机理的认识有所提高,从而在开发治疗此类疾病的方法方面取得了更大的进展。外显子跳转、基因扩增和基因编辑已成为罕见神经肌肉疾病药物研发的焦点。最近,随着 CRISPR 技术的出现,在靶向和修复突变方面的创新实际上为这些疾病的基因治疗方法的开发开辟了新的可能性。虽然这些疗法显示出令人满意的治疗效果,但其易降解性、不稳定性和毒性限制了它们的应用。因此,需要一种合适的传递载体来传递这些货物。病毒载体被认为是基因治疗的潜在递送系统;然而,相关的并发免疫原性反应和其他限制为其他非病毒系统的应用铺平了道路,如脂类、聚合物、细胞穿透肽(CPPs)以及其他有机和无机材料。本综述将重点介绍用于递送治疗货物的非病毒载体,以治疗肌肉萎缩症。
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引用次数: 0
Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context. 脊髓性肌肉萎缩症:印度的发病、诊断、治疗和临床试验的分子机制。
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Ashutosh Aasdev, Sreelekshmi R S, V Rajesh Iyer, Shivranjani C Moharir

Spinal muscular atrophy (SMA) is a neuromuscular, rare genetic disorder caused due to loss-of-function mutations in the survival motor neuron-1 (SMN1) gene, leading to deficiency of the SMN protein. The severity of the disease phenotype is inversely proportional to the copy number of another gene, SMN2, that differs from SMN1 by a few nucleotides. The current diagnostic methods for SMA include symptom-based diagnosis, biochemical methods like detection of serum creatine kinase, and molecular detection of disease-causing mutations using polymerase chain reaction (PCR), multiplex ligation-dependent probe amplification (MLPA), and exome or next-generation sequencing (NGS). Along with detection of the disease-causing mutation in the SMN1 gene, it is crucial to identify the copy number of the SMN2 gene, which is a disease modifier. Therapeutic options like gene therapy, antisense therapy, and small molecules are available for SMA, but, the costs are prohibitively high. This review discusses the prevalence, diagnosis, available therapeutic options for SMA, and their clinical trials in the Indian context, and highlights the need for measures to make indigenous diagnostic and therapeutic interventions.

脊髓性肌萎缩症(SMA)是一种神经肌肉性罕见遗传疾病,由于存活运动神经元-1(SMN1)基因发生功能缺失突变,导致SMN蛋白缺乏。疾病表型的严重程度与另一个基因 SMN2 的拷贝数成反比,SMN2 与 SMN1 的拷贝数相差几个核苷酸。目前 SMA 的诊断方法包括基于症状的诊断、检测血清肌酸激酶等生化方法,以及使用聚合酶链反应(PCR)、多重连接依赖性探针扩增(MLPA)、外显子组或下一代测序(NGS)等方法对致病突变进行分子检测。在检测 SMN1 基因致病突变的同时,确定 SMN2 基因的拷贝数也至关重要,因为 SMN2 基因是疾病的调节因子。目前已有基因治疗、反义治疗和小分子药物等治疗方法可用于 SMA,但费用高昂,令人望而却步。本综述讨论了 SMA 的发病率、诊断、现有治疗方案及其在印度的临床试验,并强调了采取措施进行本土诊断和治疗干预的必要性。
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引用次数: 0
Finding identical sequence repeats in multiple protein sequences: An algorithm. 在多个蛋白质序列中寻找相同的重复序列:一种算法
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Vikas Kumar Maurya, Madhumathi Sanjeevi, Chandrasekar Narayanan Rahul, Ajitha Mohan, Dhanalakshmi Ramachandran, Rashmi Siddalingappa, Roshan Rauniyar, Sekar Kanagaraj

In recent years, several experimental evidences suggest that amino acid repeats are closely linked to many disease conditions, as they have a significant role in evolution of disordered regions of the polypeptide segments. Even though many algorithms and databases were developed for such analysis, each algorithm has some caveats, like limitation on the number of amino acids within the repeat patterns and number of query protein sequences. To this end, in the present work, a new method called the internal sequence repeats across multiple protein sequences (ISRMPS) is proposed for the first time to identify identical repeats across multiple protein sequences. It also identifies distantly located repeat patterns in various protein sequences. Our method can be applied to study evolutionary relationships, epitope mapping, CRISPR-Cas sequencing methods, and other comparative analytical assessments of protein sequences.

近年来,一些实验证据表明,氨基酸重复与许多疾病密切相关,因为氨基酸重复在多肽段无序区域的进化中起着重要作用。尽管为此类分析开发了许多算法和数据库,但每种算法都有一些注意事项,如对重复模式中氨基酸数量和查询蛋白质序列数量的限制。为此,本研究首次提出了一种名为跨多个蛋白质序列的内部序列重复(ISRMPS)的新方法,用于识别跨多个蛋白质序列的相同重复。它还能识别各种蛋白质序列中位置较远的重复模式。我们的方法可用于研究进化关系、表位图谱、CRISPR-Cas 测序方法以及其他蛋白质序列的比较分析评估。
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引用次数: 0
Goat weed (Ageratum conyzoides L.): A biological threat to plant diversity in Eastern Ghats of India. 山羊草(Ageratum conyzoides L.):对印度东高止山植物多样性的生物威胁。
IF 2.1 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Prakash Paraseth, Kakoli Banerjee

The Kunming-Montreal Global Biodiversity Framework (GBF) is a recently signed protocol by the conference of the parties (COP 15) with an aim to protect biodiversity from risks imposed by biological threats such as invasive alien species (IAS). The present work is an effort to meet target 6 of GBF which directly deals with IAS by assessing the current and future distribution of Ageratum species in regions of the Eastern Ghats of India. Prediction of Ageratum distribution was done based on greenhouse gas emission levels, namely RCP 4.5, 6.0 and 8.5 for the climatic years 2030, 2050 and 2080. Of a total of 23 environmental parameters (19 bioclimatic, 1 land use land cover (LULC) and 3 topographic) seven were selected for species distribution modeling (SDM) considering value inflation factor (VIF) scores <3 by using maximum entropy. In the current climatic scenario, 40.09% of the geographical area (TGA) is covered by Ageratum species which will reach 76.51%, 77.44%, 82.58% for RCP 4.5, 6.0 and 8.5 respectively by the end of 2100. Both the AUC value (0.884) and Jackknife test have shown a good model performance. The Eastern Ghats, being a biodiversity-rich zone, needs efficient conservation and management strategies to decrease the extent of invaded areas to maximize biodiversity returns.

昆明-蒙特利尔全球生物多样性框架(GBF)是缔约方大会(COP 15)最近签署的一项议定书,旨在保护生物多样性免受外来入侵物种(IAS)等生物威胁带来的风险。本研究通过评估印度东高止山脉地区龙舌兰物种目前和未来的分布情况,努力实现《生物多样性框架》中直接涉及外来入侵物种的目标 6。根据 2030、2050 和 2080 气候年的温室气体排放水平,即 RCP 4.5、6.0 和 8.5,对龙舌兰的分布进行了预测。在总共 23 个环境参数(19 个生物气候参数、1 个土地利用土地覆被参数和 3 个地形参数)中,选择了 7 个参数进行物种分布建模(SDM),其中考虑到了龙舌兰物种的价值膨胀因子(VIF),到 2100 年底,RCP 4.5、6.0 和 8.5 的价值膨胀因子将分别达到 76.51%、77.44% 和 82.58%。AUC值(0.884)和积刀检验都显示了模型的良好性能。东高止山脉是生物多样性丰富的地区,需要有效的保护和管理策略来减少入侵区域的范围,从而最大限度地提高生物多样性回报。
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引用次数: 0
Comparative analysis of Quercus suber L. acorns in natural and semi-natural stands: Morphology characterization, insect attacks, and chemical composition. 天然林和半天然林中栎树橡子的比较分析:形态特征、虫害和化学成分。
IF 2.1 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Sabrina Kassouar, Dalila Mecellem, Samia Djellal, Nourelimane Benzitoune

The present study aims to investigate the differences between cork oak acorns from natural and semi-natural stands in terms of morphology, insect attack rate, and acorn chemical composition. Moreover, it examines the metabolic responses induced by insect attacks. The results show that acorns from the semi-natural stand in our study are larger than those from the natural stand. In addition, the insect attack rate was higher in the natural stand (8.25%) than in the semi-natural stand (6.25%). Furthermore, acorns in the semi-natural stand exhibit high total flavonoid content (TFC), whereas those in the natural stand are rich in total phenolic content (TPC). In terms of biochemical changes in acorns, the study revealed a remarkably significant difference in TPC, TFC, and antioxidant activity subsequent to infestation by Cydia and Curculio insects. Cydia-infested acorns from the natural stand had higher TPC levels, with a value of 93.96±0.39 mg GAE/g, showing a 17.7% increase over healthy acorns. Acorns from the semi-natural stand attacked by Curculio show the highest TFC with a value of 0.288±0.004 mg EQ/g, showing a 121.5% increase over healthy acorns. Moreover, both DPPH and FRAP methods revealed that antioxidant activity of the acorns from the semi-natural stand attacked by Curculio was more effective. This research is crucial for providing a solid foundation for the selection of highquality cork oak germplasm resources and exploring the potential valorization of insect-affected acorns in the realms of food and agriculture.

本研究旨在从形态、昆虫侵袭率和橡子化学成分等方面研究天然林和半天然林栓皮栎橡子之间的差异。此外,它还研究了昆虫攻击引起的新陈代谢反应。结果表明,在我们的研究中,来自半自然林地的橡子比来自自然林地的橡子大。此外,自然林分的虫蛀率(8.25%)高于半自然林分(6.25%)。此外,半自然林分的橡子总黄酮含量(TFC)较高,而自然林分的橡子总酚含量(TPC)丰富。在橡子的生化变化方面,研究发现,恙虫和卷叶虫侵染后,橡子的总酚、总黄酮和抗氧化活性有显著差异。受蚜虫侵染的天然林地的橡子具有较高的 TPC 含量,其值为 93.96±0.39 mg GAE/g,比健康的橡子增加了 17.7%。受到瘤蚜侵害的半自然林木的橡子的 TFC 含量最高,为 0.288±0.004 mg EQ/g,比健康橡子的 TFC 含量高出 121.5%。此外,DPPH 和 FRAP 两种方法都表明,受 Curculio 侵害的半自然林中的橡子的抗氧化活性更强。这项研究为筛选优质栓皮栎种质资源和探索受虫害影响的橡子在食品和农业领域的潜在价值奠定了坚实的基础。
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引用次数: 0
STING upregulation mediates ferroptosis and inflammatory response in lupus nephritis by upregulating TBK1 and activating NF-κB signal pathway. STING 上调通过上调 TBK1 和激活 NF-κB 信号通路介导狼疮性肾炎的铁蛋白沉着和炎症反应。
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Jinshu Chen, Pihou Chen, Yijin Song, Jiaxin Wei, Fan Wu, Jing Sun, Zhiquan Xu

Accumulated evidence implicates lipid peroxidation as a key mechanism contributing to the pathogenesis of lupus nephritis (LN). Ferroptosis is a specialized form of cell death induced by loss or deficient activity of the glutathione peroxidase 4 (GPX4) and decreased clearance of polyunsaturated fatty acid hydroperoxides. STING production may lead to the occurrence of intracellular lipid peroxidation, ultimately triggering ferroptosis, but it has not been clarified whether STING can aggravate LN via ferroptosis. The adjacent normal kidney tissues from renal cell carcinoma and biopsied kidney tissue samples from LN patients were used for research, and the expression of STING protein in kidney tissue was detected by immunohistochemistry and RT-qPCR. MRL/lpr mice, a model of LN, were used to detect STING expression in kidney tissue. STING expression in the kidney tissue of MRL/lpr mice was knocked down by sh-STING-AAV, and then levels of 4-HNE, MDA, ROS, iron ion, blood urea nitrogen and serum creatinine, IL-6, IL-1β, and TNF-α, and the protein expression of STING, TBK1, NF-κB, GPX4, ACSL4, and SLC7A11 were subsequently examined. STING was elevated in the kidney tissue of LN patients and MRL/lpr mice. Compared with the MRL/lpr group, liproxstatin-1 or ferrostatin-1 treatment alleviated ferroptosis-related indicators 4-HNE, MDA, ROS, iron ion release, and GPX4 and SLC7A1 expression, whereas the treatment enhanced ACSL4 expression. STING interference observably decreased 4-HNE, ROS, MDA, iron ion, STING, and ACSL4 levels, and increased GPX4 and SLC7A11 expression in MRL/lpr mice kidney tissues. Besides, inhibition of STING reduced kidney tissue damage and inflammatory cell infiltration in MRL/lpr mice, and levels of serum creatinine, blood urea nitrogen, serum anti-double-stranded DNA antibody, inflammatory factors IL-6, IL-1β, and TNF-α, as well as phosphorylation of NF-κB were all significantly decreased in MRL/lpr mice. TBK1 over expression reversed the impact of STING inhibition on ferroptosis and inflammatory response. STING contributed to ferroptosis and inflammatory response by activating the TBK1/NF-κB pathway, suggesting that STING may be a potent therapeutic target in LN.

累积的证据表明,脂质过氧化是导致狼疮肾炎(LN)发病机制的一个关键机制。铁变态反应是一种特殊的细胞死亡形式,由谷胱甘肽过氧化物酶 4(GPX4)的丧失或活性不足以及多不饱和脂肪酸氢过氧化物的清除减少所诱发。STING 的产生可能会导致细胞内脂质过氧化,最终引发铁变态反应,但 STING 是否会通过铁变态反应加重 LN 的病情尚未明确。研究采用肾细胞癌变邻近的正常肾组织和LN患者的活检肾组织样本,通过免疫组化和RT-qPCR检测STING蛋白在肾组织中的表达。用 LN 模型 MRL/lpr 小鼠检测 STING 在肾组织中的表达。用 sh-STING-AAV 敲低 MRL/lpr 小鼠肾组织中 STING 的表达,然后检测 4-HNE、MDA、ROS、铁离子、血尿素氮和血清肌酐、IL-6、IL-1β 和 TNF-α 的水平,以及 STING、TBK1、NF-κB、GPX4、ACSL4 和 SLC7A11 的蛋白表达。LN患者和MRL/lpr小鼠肾组织中STING升高。与 MRL/lpr 组相比,liproxstatin-1 或 ferrostatin-1 治疗可减轻铁变态反应相关指标 4-HNE、MDA、ROS、铁离子释放以及 GPX4 和 SLC7A1 的表达,而治疗则可增强 ACSL4 的表达。STING 干扰可明显降低 MRL/lpr 小鼠肾组织中的 4-HNE、ROS、MDA、铁离子、STING 和 ACSL4 水平,并增加 GPX4 和 SLC7A11 的表达。此外,抑制 STING 可减少 MRL/lpr 小鼠肾组织损伤和炎症细胞浸润,MRL/lpr 小鼠血清肌酐、血尿素氮、血清抗双链 DNA 抗体、炎症因子 IL-6、IL-1β 和 TNF-α 以及 NF-κB 磷酸化水平均显著降低。TBK1的过度表达逆转了STING抑制对铁蛋白沉积和炎症反应的影响。STING通过激活TBK1/NF-κB通路促进了铁变态反应和炎症反应,这表明STING可能是LN的一个有效治疗靶点。
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引用次数: 0
Enhancing access to treatment for Gaucher disease in India: The need for indigenous manufacturing. 提高印度戈谢病治疗的可及性:本土生产的必要性。
IF 2.9 4区 生物学 Q2 BIOLOGY Pub Date : 2024-01-01
Nidhi Patel, Heta Pandya, Ganesh Sangle, Mohua Chakraborty Choudhury

Gaucher disease (GD) is a prevalent lysosomal storage disorder (LSD) that significantly impacts individuals' lives. However, the exorbitant prices of GD medications pose a major hurdle in ensuring widespread availability and affordability of treatment in India. The country heavily relies on imported medications, leading to high costs and limited access for many patients. This article aims to address this issue by advocating for the establishment of indigenous manufacturing capabilities for GD medicines in India. Through an examination of the current landscape of GD treatment, including the availability, affordability, and challenges associated with imported medications, this article highlights the urgent need for localized production. By focusing on the potential benefits of indigenous manufacturing, such as reduced costs, increased accessibility, and enhanced availability, this research aims to provide insights and recommendations to policymakers, healthcare professionals, and relevant stakeholders. The findings underscore the importance of developing domestic manufacturing capabilities to address the affordability and accessibility challenges faced by GD patients in India. The research also emphasizes the potential positive impact on the healthcare system, the pharmaceutical industry, and the overall well-being of individuals with GD. Ultimately, this article seeks to stimulate discussions and actions towards creating a sustainable framework for indigenous manufacturing of GD medicines, thereby improving the lives of those affected by this rare and debilitating condition.

戈谢病(GD)是一种普遍存在的溶酶体储积症(LSD),对患者的生活造成严重影响。然而,高昂的戈谢病药物价格对确保治疗在印度的普及和可负担性构成了重大障碍。印度严重依赖进口药物,导致成本高昂,许多患者难以获得治疗。本文旨在通过倡导建立印度本土的 GD 药物制造能力来解决这一问题。通过考察目前的 GD 治疗情况,包括进口药物的可用性、可负担性和相关挑战,本文强调了本地化生产的迫切需要。通过关注本土生产的潜在优势,如降低成本、提高可及性和可用性,本研究旨在为政策制定者、医疗保健专业人士和相关利益方提供见解和建议。研究结果强调了发展本土制造能力的重要性,以解决印度广东快乐十分患者在经济承受能力和可及性方面面临的挑战。研究还强调了对医疗保健系统、制药行业和 GD 患者整体福祉的潜在积极影响。最终,这篇文章旨在激发讨论和行动,为本土生产 GD 药物建立一个可持续的框架,从而改善受这种罕见的衰弱病症影响的人们的生活。
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引用次数: 0
期刊
Journal of Biosciences
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