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Adequate effectiveness of ribociclib plus letrozole or fulvestrant in patients with advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated in routine Bulgarian clinical practice 在保加利亚的常规临床实践中,核波西尼联合来曲唑或氟维司汀治疗晚期或转移性激素受体阳性、人表皮生长因子受体2阴性乳腺癌患者的足够有效性
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-11 DOI: 10.1080/13102818.2023.2268753
Manoela Manova, Jeliazko Arabadjiev, Radoslav Mangaldzhiev, Assen Dudov, Daniel Penchev, Margit Hemetsberger, Arkadi Sharkov, Boryana Zidarova, Dimitrina Apostolova, Maria Vasileva, Silvia Terezova, Mila Vlaskovska, Alexandra Savova
Randomized controlled trials (RCTs) are typically conducted in highly selected patient populations to ideally demonstrate unconfounded clinical efficacy of a drug. In the real world, there may be confounding factors, such as comorbidities or less frequent monitoring. It has therefore become standard practice in many countries to validate findings from RCTs against available real-world datasets. The present analysis investigated a real-world evidence (RWE) cohort of Bulgarian patients treated with ribociclib in combination with letrozole or fulvestrant and compared the clinical benefit rate (CBR, defined as complete remission [CR] or partial remission [PR] or stable disease [SD]) and progression-free survival (PFS) and overall survival (OS) with pivotal RCTs. Data from 812 patients treated between 2018 and 2022 were used. The number of patients at risk was statistically robust to compare PFS and OS during the earlier periods of the real-world data analysis with the corresponding RCTs. Baseline characteristics (age, hormone receptor status, status of newly diagnosed vs. existing, previous treatments, performance status and tumor stage) were largely comparable between the RWE cohort and the RCTs. The RWE cohorts corroborated RCT findings of a CBR benefit of the ribociclib plus letrozole or fulvestrant combination compared to letrozole or fulvestrant alone. In the periods of adequate statistical robustness, PFS and OS were comparable within 95% confidence intervals (CIs) with RCT findings. This analysis found that patients with comparable characteristics use ribociclib in the real-world similarly to what has been investigated in the RCTs. Real-world effectiveness and outcomes of ribociclib combination therapy were comparable with observations from RCTs.
随机对照试验(rct)通常在高度选定的患者群体中进行,以理想地证明药物的无混杂临床疗效。在现实世界中,可能存在混淆因素,如合并症或监测频率较低。因此,根据现有的真实世界数据集验证随机对照试验的结果已成为许多国家的标准做法。目前的分析调查了一个真实世界证据(RWE)队列,保加利亚患者接受了核糖西尼联合来曲唑或氟维司汀治疗,并比较了临床获益率(CBR,定义为完全缓解[CR]或部分缓解[PR]或疾病稳定[SD])、无进展生存期(PFS)和总生存期(OS)与关键随机对照试验。研究使用了2018年至2022年期间接受治疗的812名患者的数据。在现实世界数据分析的早期阶段,与相应的随机对照试验相比,处于危险中的患者数量在统计学上是稳健的。基线特征(年龄、激素受体状态、新诊断与现有状态、既往治疗、表现状态和肿瘤分期)在RWE队列和随机对照试验之间具有很大的可比性。RWE队列证实了RCT结果,即与单独来曲唑或氟维司汀相比,核糖素加来曲唑或氟维司汀联合使用在CBR方面的益处。在足够的统计稳健性期间,PFS和OS与RCT结果在95%置信区间(ci)内具有可比性。该分析发现,具有相似特征的患者在现实世界中使用的核糖环尼与在随机对照试验中研究的相似。核糖素联合治疗的实际疗效和结果与随机对照试验的观察结果相当。
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引用次数: 0
TLR4 signalling protects Sertoli cells from cell stress via reprogramming inflammasome and autophagy pathways in MAPK1/ERK2 dependent way TLR4信号以MAPK1/ERK2依赖的方式通过重编程炎性体和自噬途径保护支持细胞免受细胞应激
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-09 DOI: 10.1080/13102818.2023.2268749
Elina Avramska, Ilka Tsvetkova, Krassimira Todorova, Soren Hayrabedyan
Sertoli cells constitutively maintain the spermatogonial stem cell niche and blood-testis barrier via impenetrable tight junctions under hormonal, growth factor and cytokine control. Immature Sertoli cell proliferation and survival benefit from FSH, NF-κB, and IL-1α-dependent signalling effective via the MAPK family of pathways and related to p38 MAPK dependent Ca2+ and K+ fluxes. Little is known about how the NF-κB and MAPK axis interact with pro-inflammatory NOD1/TLR4 and different voltage-gated channels. Silencing MAPK1, we found that MAPK1/ERK2 has a synergistic role with TLR4 in restricting the pro-inflammatory NF-κB/Caspase-1/IL-1β axis while having an antagonistic effect on TLR4 in promoting adult 15 P-1 Sertoli cell line proliferation and migration. In MAPK1/ERK2 absence, there was an unexpected TLR4-NF-κB behaviour, showing a strong NF-κB transactivation, assessed using a pNIFTY-SEAP reporter plasmid, accompanied by significantly activated cell migration and proliferation, as demonstrated by the wound healing assay. Voltage-gated potassium flux, most likely via Kv1.3, was significantly increased after TLR4 and NOD1 challenge in ATP DAMP signal presence, associated with inflammasome activation. TLR4 challenge also activated macroautophagy while inhibiting mitophagy. Thus, TLR4 activation restricted the NF-κB and Caspase-1/IL-1β pro-inflammatory axis, cell migration and proliferation, voltage-gated potassium efflux, and shifted mitophagy to macroautophagy (towards an inflammasome pathway-related cell death), promoting cell survival. MAPK1/ERK2 had a differential effect, as in its absence, TLR4 activation had the opposite effect on NF-κB transactivation and cell migration and proliferation. Thus, TLR4/MAPK1/NF-κB/Kv1.3 interaction provides optimal Sertoli cell maintenance conditions and allows cell death only in extreme circumstances of cumulative DAMP/PAMP signalling stimulation.
在激素、生长因子和细胞因子的控制下,支持细胞通过不可穿透的紧密连接维持着精原干细胞生态位和血睾丸屏障。未成熟的支持细胞增殖和存活受益于FSH、NF-κB和il -1α依赖的信号,这些信号通过MAPK家族途径有效,并与p38 MAPK依赖的Ca2+和K+通量相关。关于NF-κB和MAPK轴如何与促炎NOD1/TLR4和不同电压门控通道相互作用,我们知之甚少。通过沉默MAPK1,我们发现MAPK1/ERK2与TLR4具有协同作用,可以抑制促炎的NF-κB/Caspase-1/IL-1β轴,而对TLR4具有拮抗作用,可以促进成人15p -1支持细胞系的增殖和迁移。在MAPK1/ERK2缺失的情况下,出现了意想不到的TLR4-NF-κB行为,显示出强烈的NF-κB转激活,使用pNIFTY-SEAP报告质粒进行评估,并伴随着显著激活的细胞迁移和增殖,如伤口愈合试验所示。在ATP DAMP信号存在的情况下,TLR4和NOD1激活后,电压门控钾通量(最有可能通过Kv1.3)显著增加,与炎症小体激活有关。TLR4挑战也激活了巨噬,同时抑制了有丝分裂。因此,TLR4的激活限制了NF-κB和Caspase-1/IL-1β促炎轴、细胞迁移和增殖、电压门控钾外溢,并将有丝分裂转变为巨噬(向炎性小体途径相关的细胞死亡方向发展),促进细胞存活。MAPK1/ERK2具有不同的作用,因为在其缺失的情况下,TLR4的激活对NF-κB的反激活和细胞迁移和增殖具有相反的作用。因此,TLR4/MAPK1/NF-κB/Kv1.3相互作用提供了最佳的支持细胞维持条件,并且仅在累积的DAMP/PAMP信号刺激的极端情况下才允许细胞死亡。
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引用次数: 0
Microsatellite unstable colorectal cancers are associated with increased CD1a- and CD83-positive dendritic cell infiltration 微卫星不稳定结直肠癌与CD1a-和cd83阳性树突状细胞浸润增加有关
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-05 DOI: 10.1080/13102818.2023.2266517
Maya Gulubova, Elina Aleksandrova, Yovcho Yovchev, Dimitar Chonov, Petio Chilingirov, Tatyana Vlaykova
Microsatellite instability (MSI) is characterized by a highly immunogenic tumor phenotype and abundant lymphocytic infiltrates. The aim of this study was to investigate the association between four immunohistochemically determined classes of dendritic cells (DC) with microsatellite instability status of 258 colorectal cancer (CRC) patients and to explore the possible role of those cells as prognostic factors for survival. We observed a distinct infiltration pattern of DCs both in tumor stroma (TS) and invasive front (IF), with DCs significantly prevailing in the IF (p < 0.0001). MSI cancer biopsies showed significantly higher infiltration of CD1a + and CD83+ DCs in the TS and IF compared to microsatellite stable CRCs. Survival analysis revealed that higher CD1a + and CD83+ DC numbers both in TS and IF correlated with longer survival of the patients after surgical therapy (p < 0.05, Log rank test). Cox multivariate analysis showed that lower infiltration with CD1a + DCs in TS (p = 0.039) and CD83+ DCs in IF (p = 0.022) was an independent prognostic factor for unfavorable outcome for CRC patients. The results of our study suggest that the immunohistochemically determined CD1a + and CD83+ DCs could be used as a feature of microsatellite instability and could be further explored as prognostic markers for patients’ outcome.
微卫星不稳定性(MSI)的特点是高度免疫原性的肿瘤表型和丰富的淋巴细胞浸润。本研究的目的是研究258名结直肠癌(CRC)患者的四种免疫组织化学测定的树突状细胞(DC)与微卫星不稳定状态之间的关系,并探讨这些细胞作为生存预后因素的可能作用。我们观察到dc在肿瘤间质(TS)和浸润前缘(IF)中有明显的浸润模式,其中dc在浸润前缘明显占优(p < 0.0001)。MSI肿瘤活检显示,与微卫星稳定的crc相比,TS和IF中CD1a +和CD83+ dc的浸润明显更高。生存分析显示,TS和IF患者的CD1a +和CD83+ DC数越高,手术后患者的生存时间越长(p < 0.05, Log rank检验)。Cox多因素分析显示,TS中CD1a + DCs的低浸润(p = 0.039)和IF中CD83+ DCs的低浸润(p = 0.022)是CRC患者预后不良的独立预后因素。我们的研究结果表明,免疫组织化学测定的CD1a +和CD83+ dc可以作为微卫星不稳定性的特征,并可以进一步探索作为患者预后的预后指标。
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引用次数: 0
Overexpression of GhSWEET42 , a SWEET -like gene from cotton, enhances the oil content and seed size 棉花中类似SWEET的基因GhSWEET42的过表达可以提高含油量和种子大小
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-04 DOI: 10.1080/13102818.2023.2266529
Deying Wang, Mengxue Du, Jingyu Li, Shuwen Yin, Yongwang Sun, Shangjing Guo
SWEET (‘sugars will eventually be exported transporters’) family genes reportedly play a critical role in sugar translocation and oil biosynthesis in various plant species. However, their functions in cotton are unknown. The present study demonstrated that while GhSWEET42 was widely expressed in different cotton tissues, it had the highest expression level in the developing ovules. Hence, it performs a vital role in seed development. We constructed GhSWEET42 transgenic Arabidopsis lines to verify the biological function of this gene and found that the oil content and weight of the seeds produced by the overexpression lines were 18–23% and 19–20% higher, respectively than those of the wild-type. Gas chromatography–mass spectrometry (GC–MS) analysis revealed that it was mainly a relative increase in unsaturated fatty acids (FAs) that contributed to the relative increase in oil content in the transgenic seeds. Moreover, the latter exhibited comparative upregulation of certain genes associated with FA and triacylglycerol biosynthesis as well as cell expansion. GhSWEET42 might work synergistically with the aforementioned genes. This finding indicates that GhSWEET42 may be essential in oil biosynthesis and seed development in cotton. The results of the present work may facilitate further explorations into the molecular mechanism of cottonseed oil biosynthesis as well as the cultivation of novel oil-rich cotton varieties.
据报道,SWEET(“糖最终会被输出转运体”)家族基因在多种植物的糖转运和油脂生物合成中起着关键作用。然而,它们在棉花中的作用尚不清楚。本研究表明,虽然GhSWEET42在棉花不同组织中广泛表达,但在发育中的胚珠中表达量最高。因此,它在种子发育中起着至关重要的作用。为了验证该基因的生物学功能,我们构建了转基因GhSWEET42拟南芥品系,结果发现,过表达品系生产的种子含油量和重量分别比野生型高18-23%和19-20%。气相色谱-质谱(GC-MS)分析表明,转基因种子含油量的相对增加主要是由于不饱和脂肪酸(FAs)含量的相对增加。此外,后者表现出与FA和甘油三酯生物合成以及细胞扩增相关的某些基因的相对上调。GhSWEET42可能与上述基因协同作用。这一发现表明GhSWEET42可能在棉花油脂生物合成和种子发育中起重要作用。本研究结果为进一步探索棉籽油生物合成的分子机制和培育富油棉花新品种提供了理论依据。
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引用次数: 0
Bigel formulations of St. John’s wort extract in wound healing: toxicological aspects 圣约翰草提取物在伤口愈合中的Bigel配方:毒理学方面
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-27 DOI: 10.1080/13102818.2023.2263570
Yoana Sotirova, Deyana Vankova, Oskan Tasinov, Stefka Stoeva, Minka Hristova, Ivelin Iliev, Svetlana Georgieva, Yoana Kiselova-Kaneva, Velichka Andonova
This study aimed to investigate the toxicological profile of hyperforin (HP) in silico and to assess it in vivo after topical application of an HP-rich St. John’s wort (SJW) extract. The former analysis predicted low toxicity because of HP’s inability to bind DNA or proteins, but structural alerts for skin irritation/corrosion, carcinogenicity, and mutagenicity were found. Animal studies involved the treatment of excision wounds in Wistar rats with poloxamer 407/borage oil formulations (bigels; Bs) containing HP-rich SJW extract previously developed by us. The effects of semisolids comprising ‘free’ extract (B/SJW) or extract loaded in nanostructured lipid carriers (B/NLC-SJW) were compared to positive (commercial herbal product) and negative (untreated) controls after 2-, 7-, 14-, and 21-day applications. Malondialdehyde (MDA) and ABTS assays evaluated the degree of oxidative stress—treatment with bigels did not affect MDA favorably but led to an increased radical-cation scavenging capacity (compared to controls). Gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactate dehydrogenase (LDH) enzyme levels were measured as indicators for liver/tissue damage. Treatment with both B/SJW and B/NLC-SJW for 21 days resulted in lower GGT and ASAT levels than those in controls. Two-day application of the biphasic semisolids contributed to normalized ALAT levels (lower than in both negative and positive controls), and the same trends were observed in LDH levels after a 7-day treatment. The promising results obtained after the B/NLC-SJW application suggest that this drug delivery system may not only preserve HP in SJW extract effectively but also ‘expose’ its cyto-/hepatoprotective potential.
本研究旨在研究富含HP的St. John’s wort (SJW)提取物外用后,HP在硅片中的毒理学特征,并在体内评估其毒性。前一种分析预测HP的毒性较低,因为它不能结合DNA或蛋白质,但发现了对皮肤的刺激/腐蚀、致癌性和诱变性的结构警告。动物研究涉及使用poloxam407 /琉璃苣油制剂(bigels;b)含有我们先前开发的富含hp的SJW提取物。在2、7、14和21天的应用后,将含有“游离”提取物(B/SJW)或纳米结构脂质载体(B/NLC-SJW)提取物的半固体与阳性(商业草药产品)和阴性(未处理)对照进行比较。丙二醛(MDA)和ABTS测定评估氧化应激的程度,用bigels处理对MDA没有有利影响,但导致自由基阳离子清除能力增加(与对照组相比)。测定γ -谷氨酰转移酶(GGT)、天冬氨酸转氨酶(ASAT)、丙氨酸转氨酶(ALAT)和乳酸脱氢酶(LDH)水平,作为肝/组织损伤的指标。B/SJW和B/NLC-SJW治疗21天,GGT和ASAT水平低于对照组。双相半固体治疗2天后,ALAT水平恢复正常(低于阴性对照组和阳性对照组),LDH水平在治疗7天后也出现了相同的趋势。B/NLC-SJW应用后获得的可喜结果表明,该给药系统不仅可以有效地保存SJW提取物中的HP,而且可以“暴露”其细胞/肝脏保护潜力。
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引用次数: 0
Enhancement of taxane production in cell suspension culture of Corylus avellana L. Kalınkara by elicitation and precursor feeding 诱导和前体摄食提高榛树悬浮培养Kalınkara细胞紫杉烷产量
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-26 DOI: 10.1080/13102818.2023.2255703
Ilayda Goktepe-Atilgan, Ahmet Dogan, Sule Ari
Paclitaxel (trademark Taxol®) is the most effective chemotherapeutic agent against a wide range of cancers. Hazelnut (Corylus avellana L.) cell culture is a promising and inexpensive strategy for producing paclitaxel and related taxanes. This study evaluated the effect of elicitation and taxane precursor feeding for the enhancement of taxanes in a Turkish hazelnut (C. avellana cv. ‘Kalınkara’) cell suspension culture. Elicitor methyl jasmonate (100, 200 and 300 µmol L−1) and precursor phenylalanine (3μmol, 3 and 6 mmol L−1) were tested in cell suspension cultures. While methyl jasmonate increased the accumulation of taxanes, especially cephalomannine, via induction of the paclitaxel biosynthetic pathway, phenylalanine slightly induced the conversion of 10-deacetylbaccatin III and baccatin III to the end product paclitaxel (0.5349 µg g−1). The results showed that 200 µmol L−1 methyl jasmonate led to significantly greater induction of taxanes than 100 and 300 µmol L−1. The amount of cephalomannine (331.6 µg g−1) in cell suspension cultures elicited by 200 µmol L−1 methyl jasmonate was 8-fold higher than that in the control (41.61 µg g−1), while 10-deacetylbaccatin III (6.174 µg g−1) and baccatin III (3.956 µg g−1) increased almost twice as much as the control. The highest total paclitaxel yield was 5.453 µg g−1 in the same culture conditions. In conclusion, cell culture systems of C. avellana L. cv. ‘Kalınkara’ hazelnut, established for the first time, may become a potential candidate for industrial-level production of cephalomannine and other taxanes with further optimization.
紫杉醇(商标紫杉醇®)是治疗多种癌症最有效的化疗药物。榛子细胞培养是生产紫杉醇及相关紫杉烷的一种有前途且廉价的方法。本研究评估了激发和投喂紫杉烷前体对土耳其榛子(C. avellana cv.)中紫杉烷的增强作用。' Kalınkara ')细胞悬浮培养。在细胞悬浮培养中检测激发子茉莉酸甲酯(100、200和300 μmol L−1)和前体苯丙氨酸(3μmol、3和6 mmol L−1)。茉莉酸甲酯通过诱导紫杉醇生物合成途径,增加了紫杉烷的积累,尤其是头甘氨酸,而苯丙氨酸则轻微诱导10-去乙酰baccatin III和baccatin III转化为最终产物紫杉醇(0.5349µg g−1)。结果表明,200µmol L−1茉莉酸甲酯对紫杉烷的诱导作用显著高于100和300µmol L−1。在200µmol L−1茉莉酸甲酯诱导的细胞悬浮培养中,头甘氨酸(331.6µg g−1)的含量是对照(41.61µg g−1)的8倍,而10-去乙酰baccatin III(6.174µg g−1)和baccatin III(3.956µg g−1)的含量几乎是对照的两倍。在相同的培养条件下,紫杉醇总产量最高,为5.453µg g−1。综上所述,黄花苜蓿的细胞培养体系。首次建立的“Kalınkara”榛子,通过进一步优化,可能成为工业化生产头甘氨酸和其他紫杉烷的潜在候选者。
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引用次数: 0
Flaxseed protein isolate-alginate microbeads as encapsulating agents for enhanced survival of Enterococcus faecalis HZNU S1 during storage and in vitro gastrointestinal conditions 亚麻籽分离蛋白-海藻酸盐微球作为包封剂提高粪肠球菌HZNU S1在储存和体外胃肠道条件下的存活率
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-23 DOI: 10.1080/13102818.2023.2262625
Zhen-Xing Tang, Zheng Xu, Qing-Nan Ma, Xue-Yan Chen, Hang-Qi Chen, Yu-Jie Cao, Tao-Yang Zhang, Zhen-Bo Yao, Lu-E Shi
This study aimed to study the entrapment of Enterococcus faecalis HZNU S1 using a mixture of flaxseed protein isolate (FPI) and sodium alginate (SA) as an encapsulation agent. The characteristics of free and encapsulated cells during storage and under in vitro gastrointestinal conditions were investigated. The survival rate of encapsulated cells did not decline after 2 h exposure to pH 2.5 simulated gastric juice (SGJ), while viable free probiotics treated at the same conditions, were not found. After encapsulated probiotics were exposed to SGJ pH 2.0 for 2.0 h, the viability decreased from 10.01 to 8.01 Log CFU/g. After exposure to 1.0% and 2.0% bile salt solutions for 2 h, the viable amounts of encapsulated probiotics were still higher 8.0 Log CFU/g, whereas, viable free cells were not observed after treatment at the same conditions. Encapsulated probiotics were fully released from the microbeads in simulated intestinal juice (SIJ) in around 4 h. The viable numbers of encapsulated probiotics were only reduced 0.5 Log CFU/g after two weeks of storage (4 °C), and the viable amounts of encapsulated probiotics were reduced to 8.2 Log CFU/g at 25 °C after eight days of storage. However, the viable amounts of free cells were reduced from 10.01 to 8.8 Log CFU/mL (4 °C), and 4.0 Log CFU/mL (25 °C) during the investigated storage period, respectively. Encapsulated E. faecalis HZNU S1 showed enhanced resistance to environmental conditions, allowing the delivery of probiotics that could be used to increase foods added value.
以亚麻籽分离蛋白(FPI)和海藻酸钠(SA)为包封剂,研究粪肠球菌HZNU S1的包封效果。研究了游离细胞和包被细胞在体外胃肠道条件下的贮藏特性。pH为2.5的模拟胃液(SGJ)处理2 h后,囊化细胞的存活率没有下降,而在相同条件下,未发现有活力的游离益生菌。包封后的益生菌在pH 2.0的SGJ中暴露2.0 h后,其活力从10.01 Log CFU/g下降到8.01 Log CFU/g。在1.0%和2.0%胆盐溶液中处理2 h后,包封益生菌的活菌量仍高于8.0 Log CFU/g,而在相同条件下处理后,未观察到活的游离细胞。被封装的益生菌在4 h左右从模拟肠液(SIJ)中的微珠中完全释放出来。在4℃的贮藏2周后,被封装的益生菌活菌数仅减少0.5 Log CFU/g,在25℃的贮藏8天后,被封装的益生菌活菌量减少到8.2 Log CFU/g。然而,在实验期间,游离细胞的活菌量分别从10.01降至8.8 Log CFU/mL(4°C)和4.0 Log CFU/mL(25°C)。包封的粪肠杆菌HZNU S1对环境条件的抵抗力增强,允许益生菌的传递,可用于增加食品的附加值。
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引用次数: 0
A study of anti-SARS-CoV-2 antibodies among healthcare personnel and the general population 医务人员与普通人群抗sars - cov -2抗体的研究
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-14 DOI: 10.1080/13102818.2023.2256417
Iva Trifonova, Kim Ngoc, Teodora Gladnishka, Vladislava Ivanova, Metodi Kunchev, Ventsislav Mutafchiyski, Iva Christova
Bulgaria, like many other countries, has experienced the far-reaching consequences of the Coronavirus disease 2019 (COVID-19) pandemic. Seroprevalence studies serve as a crucial method for assessing the exposure and immunity levels within a population. In this serosurvey, which is the first of this kind conducted in Bulgaria, we enrolled 104 healthcare workers (HCWs) from one front-line Bulgarian hospital and 237 individuals from the general population. Serum samples were collected in December 2021 from the general population and in February 2023 from HCWs and the general population. The presence of four anti-SARS-CoV-2 antibodies was evaluated: anti-Spike 1-IgG, anti-Nucleoprotein-IgG, anti-Spike1-IgA and anti-Recombinant binding domain neutralizing antibodies. Our results showed high percentages of seropositivity in both the HCWs and the general population (99% and 78%, respectively) in February 2023. HCWs had significantly higher mean IgA and mean anti-S1-IgG antibody levels compared to the general population. The seropositivity in the general population in December 2021 was 79%. The mean levels of IgA and anti-NCP-IgG were significantly higher, whereas the mean anti-S1-IgG levels were significantly lower in February 2023 compared to December 2021. We found a strong correlation between neutralizing antibodies and anti-S1-IgA and anti-S1-IgG antibodies for all tested groups. It is necessary to perform large-scale serosurveys to provide analysis of the seroprevalence in a larger population and its dynamics over time and to facilitate evidence-based strategies that will safeguard the health and well-being of the Bulgarian population and contribute to the global efforts in combating the COVID-19 pandemic.
与许多其他国家一样,保加利亚经历了2019年冠状病毒病(COVID-19)大流行的深远影响。血清阳性率研究是评估人群暴露和免疫水平的重要方法。在保加利亚首次进行的这项血清调查中,我们招募了来自保加利亚一家一线医院的104名卫生保健工作者(HCWs)和来自普通人群的237名个人。于2021年12月和2023年2月分别从普通人群和卫生保健工作者和普通人群中采集血清样本。检测四种抗sars - cov -2抗体的存在:抗spike 1-IgG、抗核蛋白- igg、抗spike1 - iga和抗重组结合域中和抗体。我们的结果显示,在2023年2月,HCWs和一般人群的血清阳性率都很高(分别为99%和78%)。与普通人群相比,HCWs患者的IgA和抗s1 - igg抗体水平显著升高。2021年12月,普通人群血清阳性率为79%。与2021年12月相比,2023年2月IgA和抗ncp - igg的平均水平显著升高,而抗s1 - igg的平均水平显著降低。我们发现在所有测试组中,中和抗体与抗s1 - iga和抗s1 - igg抗体之间存在很强的相关性。有必要开展大规模血清调查,分析更大人群中的血清患病率及其随时间变化的情况,并促进基于证据的战略,以保障保加利亚人口的健康和福祉,并为全球抗击COVID-19大流行的努力做出贡献。
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引用次数: 0
Serum sRAGE, sRANKL and osteoprotegerin in subgroups of rheumatoid arthritis patients: biomarkers associated with iron and disease status 类风湿关节炎亚组患者血清sRAGE、sRANKL和骨保护素:与铁和疾病状态相关的生物标志物
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-07 DOI: 10.1080/13102818.2023.2256428
Ginka Delcheva, Katya Stefanova, Teodora Stankova
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引用次数: 0
Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients 利伯氏遗传性视神经病变:保加利亚患者的临床和遗传分析
4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-05 DOI: 10.1080/13102818.2023.2255073
Sylvia Cherninkova, Boryana Zaharova, Kunka Kamenarova, Kalina Mihova, Slavena Atemin, Tihomir Todorov, Vasil Haykin, Alexander Oscar, Ivailo Tournev, Radka Kaneva, Albena Todorova
Leber’s hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA) genes encoding subunits of complex I in the mitochondrial respiratory chain. The most common mutations causing LHON are G11778A, G3460A and T14484C, but there are also several less common mutations. LHON presents as acute or subacute bilateral visual loss, usually affecting young males. The aim of this study was to assess the clinical symptomatology and genetic analysis of Bulgarian patients with LHON. Twenty-two patients were diagnosed with LHON based on clinical evaluation and genetic examination (17 males and 5 females); 12 of them were previously reported, while 8 males and 2 females are newly diagnosed. A full neuroophthalmologic and genetic examination was performed. Eight patients had a family history of LHON, while 14 were isolated cases. The age at onset ranged from 3 to 43 years, and visual acuity ranged from counting fingers to 0.9. Genetic testing revealed various mutations, including a rare mutation G3635A in MT-ND1 in five affected members of one pedigree and digenic inheritance of G11778A and T14484C in three individuals from a different family. A variant m.15988A > G in the mitochondrial gene MT-TP with a high level of heteroplasmy was found in one patient. In addition to the most common mutations causing LHON, our patients also had rare mutations. These results suggest that genetic analysis of the entire mtDNA sequence is recommended in cases with strong clinical suspicion of LHON, since new rare mtDNA pathogenic variants are being identified.
Leber 's遗传性视神经病变(LHON)是一种罕见的由线粒体DNA (mtDNA)基因编码线粒体呼吸链复合体I亚基突变引起的母系遗传性疾病。导致LHON最常见的突变是G11778A、G3460A和T14484C,但也有几种不太常见的突变。LHON表现为急性或亚急性双侧视力丧失,通常影响年轻男性。本研究的目的是评估保加利亚LHON患者的临床症状和遗传分析。经临床评价和遗传检查诊断为LHON的患者22例(男17例,女5例);其中12例是以前报告的,而8名男性和2名女性是新诊断的。进行了全面的神经眼科和遗传学检查。8例患者有LHON家族史,14例为孤立病例。发病年龄3 ~ 43岁,视力从数指到0.9。基因检测显示了多种突变,包括一个家系的5名受影响成员MT-ND1中罕见的G3635A突变,以及来自不同家庭的3名个体的G11778A和T14484C基因遗传。1例患者线粒体MT-TP基因变异m.15988A > G,异质性高。除了导致LHON的最常见的突变外,我们的患者也有罕见的突变。这些结果表明,在临床强烈怀疑LHON的病例中,建议对整个mtDNA序列进行遗传分析,因为正在发现新的罕见mtDNA致病变异。
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Biotechnology & Biotechnological Equipment
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