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Imbalance of Antioxidant Processes in Red Blood Cells—A Universal Factor of Pathogenesis of Cancer-Associated Anemia 红细胞抗氧化过程失衡——癌症相关性贫血发病的一个普遍因素
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750824601395
E. M. Bakurova, Yu. D. Tursunova, N. M. Dobaeva, K. I. Zolotareva, E. V. Butenko

The features of free radical oxidation in red blood cells coupled with the development of anemia in non-small cell lung cancer and breast cancer have been studied. In cancer, the imbalance of antioxidant enzymes activities was detected in red blood cells. For example, a 2-fold increase in the activity of superoxide dismutase (SOD) on the average (p < 0.001) was accompanied by a 1.5-fold decrease in the activity of glutathione peroxidase (GPO) (p < 0.005). According to the Spearman’s rank correlation, the decrease in GPO activity is coupled with the development of anemia, correlates with the decrease in hemoglobin (Hb) and hematocrit (HTC). The values of Spearman’s rank correlation coefficient are ρ = 0.76 for GPO and Hb; ρ = 0.74 for GPO and HTC. Anemia develops under the conditions of intensification of pro-oxidant processes and impaired gas transport function of red blood cells, as is demonstrated by positive correlation between the levels of malonic dialdehyde and 2,3-diphosphoglycerate (ρ = 0.54), which increased during its development (ρ = 0.74). The revealed impairments are universal and have been observed both in non-small cell lung cancer and in breast cancer.

研究了非小细胞肺癌和乳腺癌中红细胞自由基氧化与贫血发展的关系。在癌症中,在红细胞中检测到抗氧化酶活性的不平衡。例如,超氧化物歧化酶(SOD)活性平均增加2倍(p < 0.001)的同时,谷胱甘肽过氧化物酶(GPO)活性平均下降1.5倍(p < 0.005)。根据Spearman等级相关性,GPO活性的降低与贫血的发生有关,与血红蛋白(Hb)和红细胞压积(HTC)的降低相关。GPO和Hb的Spearman等级相关系数ρ = 0.76;GPO和HTC的ρ = 0.74。贫血是在促氧化过程增强和红细胞气体输送功能受损的条件下发展起来的,正如丙二醛和2,3-二磷酸甘油酸水平之间的正相关(ρ = 0.54)所证明的那样,在其发展过程中,丙二醛和2,3-二磷酸甘油酸的水平增加(ρ = 0.74)。所揭示的损伤是普遍的,在非小细胞肺癌和乳腺癌中都有观察到。
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引用次数: 0
Hepatitis C Specificity in Lowering Serum Lipids of Patients with Chronic Renal Failure 丙型肝炎特异性降低慢性肾衰竭患者的血脂
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750824600948
Marwa Adnan Jabbar,  Jawad Kadhum Muraih

This study describes the effects of the hepatitis C virus on lipid profile and some other parameters in patients with CRF. A clinical comparison was made between CRF patients with and without the hepatitis C virus. Abnormal lipid profiles in most patients with CRF are represented by high levels of serum cholesterol, triglyceride, LDL, and VLDL, and low levels of serum HDL cholesterol. While there was a lowering in serum cholesterol, triglyceride, LDL, and VLDL levels in CRF patients with hepatitis C infection, there is a positive association between the progression of CRF and fasting serum TG and cholesterol, regardless of age or gender, and the DM state of patients. HCV viral infection appeared to be related to decreased blood cholesterol and triglyceride levels, demonstrating that the HCV virus might possess a significant influence on the lipid profile within the serum of patients with chronic HCV infection. HCV binding to plasma lipoproteins has previously been demonstrated, as has the relationship between HCV infection and hypobetalipoproteinemia. The LDL receptor was additionally proposed to be one of the HCV receptors involved in HCV endocytosis, with LDL in the blood of patients effectively modulating HCV attachment to its target. HCV and LDL receptors could serve as competing inhibitors of LDL binding in HCV-infected individuals, creatinine and urea levels were elevated in HCV patients, reflecting renal abnormalities. HCV enables direct infection of renal tubular cells that contain ACE2 receptors on their surfaces.

本研究描述了丙型肝炎病毒对慢性肾功能衰竭患者血脂和其他一些参数的影响。对携带和不携带丙型肝炎病毒的CRF患者进行了临床比较。大多数CRF患者的血脂异常表现为血清胆固醇、甘油三酯、LDL和VLDL水平高,血清HDL胆固醇水平低。虽然CRF合并丙型肝炎感染的患者血清胆固醇、甘油三酯、LDL和VLDL水平降低,但无论年龄或性别,CRF的进展与空腹血清TG和胆固醇与患者的糖尿病状态呈正相关。HCV病毒感染似乎与血液胆固醇和甘油三酯水平降低有关,表明HCV病毒可能对慢性HCV感染患者的血清脂质谱有显著影响。丙型肝炎病毒与血浆脂蛋白结合,以及丙型肝炎病毒感染与低脂蛋白血症之间的关系先前已得到证实。此外,LDL受体被认为是参与HCV内吞作用的HCV受体之一,患者血液中的LDL可有效调节HCV对其靶标的附着。HCV和LDL受体在HCV感染个体中可作为LDL结合的竞争性抑制剂,HCV患者肌酐和尿素水平升高,反映肾脏异常。HCV可直接感染表面含有ACE2受体的肾小管细胞。
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引用次数: 0
Relationship between the Level of Alcohol Use and the Concentrations of Some Neuropeptides and Proteins in Blood Serum 酒精使用水平与血清中某些神经肽和蛋白质浓度的关系
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750825600281
K. A. Popov, I. M. Bykov, G. A. Ermakova

The development of novel highly informative approaches to the assessment of chronic alcohol use is still an urgent problem, especially against the background of increase in alcohol dependence detected in 2023 in Russia for the first time over the past two decades. The present study was aimed at evaluating the level of the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neuropeptide Y (NPY), and pituitary adenylate cyclase-activating peptide (PACAP) in the blood of tested subjects with different levels of alcohol use. For this purpose, the following groups of subjects were formed: healthy persons (group 1, n = 10), persons with periodical alcohol use (group 2, n = 10), persons with the consequences of using alcohol (group 3, n = 10), persons with the alcohol dependence syndrome in the acute phase (group 4, n = 10), and persons undergoing rehabilitation (group 5, n = 10). The studies have shown a relationship between ethanol consumption levels and the serum concentration of BDNF, which was 20%, 2.5 times and 40% lower relative to the control in patients from group 3, group 4 and group 5, respectively. The NPY concentration was 2.3-fold and 4.3-fold higher in the blood serum of patients from groups 2 and 3, respectively. The GDNF and PACAP levels in the blood of subjects from groups 2–5 were not significantly different from the control. The changes in the BDNF level are probably associated with the formation of new neuroadaptations and the unbalance of neuromediators typical of the dependence syndrome. The changes in the level of NPY are most likely a responce to an acute stress, more typical of subjects with the initial forms of alcoholic disorder. Thus, with BDNF and NPY used as markers, it is possible to objectify the strategy of differential diagnostics of mental and behavioral disordes associated with alcohol use. Evaluation of changes in these markers allows differentaition of persons periodically using alcohol without the development of complications and persons with harmful use of alcohol.

开发新的高信息量的方法来评估慢性酒精使用仍然是一个紧迫的问题,特别是在过去二十年来俄罗斯首次在2023年检测到酒精依赖增加的背景下。本研究旨在评价脑源性神经营养因子(BDNF)、神经胶质细胞系源性神经营养因子(GDNF)、神经肽Y (NPY)和垂体腺苷酸环化酶激活肽(PACAP)在不同饮酒水平受试者血液中的水平。为此,我们将受试者分成以下几组:健康人(第1组,n = 10)、周期性饮酒者(第2组,n = 10)、有饮酒后果的人(第3组,n = 10)、急性期酒精依赖综合征患者(第4组,n = 10)和正在康复的人(第5组,n = 10)。研究表明,乙醇消耗水平与血清BDNF浓度之间存在关系,3组、4组和5组患者的血清BDNF浓度分别比对照组低20%、2.5倍和40%。2组和3组患者血清NPY浓度分别高出2.3倍和4.3倍。2 ~ 5组受试者血液中GDNF和PACAP水平与对照组无显著差异。BDNF水平的变化可能与新的神经适应的形成和依赖综合征典型的神经介质的不平衡有关。NPY水平的变化很可能是对急性压力的反应,更典型的是最初形式的酒精障碍的受试者。因此,使用BDNF和NPY作为标记物,有可能客观化与酒精使用相关的精神和行为障碍的鉴别诊断策略。通过对这些指标变化的评估,可以区分无并发症的周期性饮酒者和有害饮酒者。
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引用次数: 0
Regenerative Medicine Technologies in Dentistry: Tissue Engineering in Dental Implantation 牙科再生医学技术:牙种植的组织工程
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750825600232
A. B. Kazumova

In recent years, regenerative medicine technologies, especially tissue engineering, have been increasingly used in dental implant surgeries. This review examines the main bioengineering trends that contribute to the success and longevity of dental implants. Since traditional implantation methods often face problems associated with insufficient integration of the implant into the alveolar bone tissue, innovative approaches such as the use of modified biomaterials, stem cells and growth factors open new horizons for improving clinical outcomes. Particular attention is paid to the development of multifunctional biomaterials that promote bone-tissue regeneration and improve osseointegration. Methods aimed at creating three-dimensional structures that imitate natural tissues are also considered. The review emphasizes an interdisciplinary approach that integrates knowledge from biology, engineering, and dentistry, which, in turn, facilitates the creation of individualized treatment strategies. In conclusion, this review highlights the importance of further research in tissue engineering to achieve higher standards in dental implantation and patient quality of life.

近年来,再生医学技术,特别是组织工程技术在种植牙手术中的应用越来越广泛。本文综述了促进种植体成功和寿命的主要生物工程趋势。由于传统的种植方法经常面临种植体与牙槽骨组织融合不足的问题,使用改良生物材料、干细胞和生长因子等创新方法为改善临床结果开辟了新的视野。特别关注的是促进骨组织再生和改善骨整合的多功能生物材料的发展。还考虑了旨在创建模仿自然组织的三维结构的方法。这篇综述强调了一种跨学科的方法,将生物学、工程学和牙科的知识整合在一起,从而促进了个性化治疗策略的创建。总之,这篇综述强调了在组织工程方面进一步研究的重要性,以达到更高的种植标准和患者的生活质量。
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引用次数: 0
Potential Influence of Tryptophan Metabolites on Translocation of Bacterial DNA into the Blood in Normal Conditions and in Various Obesity Phenotypes 色氨酸代谢物对正常情况下和各种肥胖表型下细菌DNA转运到血液中的潜在影响
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750825600141
O. P. Shatova, I. M. Kolesnikova, A. M. Gaponov, S. A. Roumiantsev, A. V. Shestopalov

It is known that obesity changes the permeability of the intestinal wall, including for bacterial DNA. Therefore, obese patients differ from healthy individuals both in the content of bacterial DNA in the blood and in microbiotic metabolites. Indole metabolites are specific products of tryptophan conversion by intestinal microbiota. Some indoles are involved in the regulation of tight junction protein expression and are, thus, important for the regulation of intestinal permeability. The aim of our study was to investigate the relationship between the content of tryptophan metabolites in feces and the level of bacterial DNA in the blood. Materials and methods. The study included healthy donors without obesity (n = 138) and patients with obesity (n = 128) who were divided into subgroups with MHO (metabolically healthy obesity) and MUHO (metabolically unhealthy obesity). Bacterial DNA was isolated from venous blood samples, and metagenomic sequencing of the v3–v4 variable region of the 16S rRNA gene was performed. Both the frequency of isolation of individual taxa from samples and the share of these taxa in the total pool of bacterial DNA in the blood were compared. Concentrations of tryptophan metabolites in fecal extracts were determined by high-performance liquid chromatography with mass spectrometry. Chromatographic separation was performed using a Discovery PFP HS analytical column; a mass spectrometric detector based on an Agilent 6470 MRM triple quadrupole and electrospray ionization was used for detection. Results. Similar decreases in the content of metabolites of the kynurenine and indole pathways of tryptophan catabolism are noted in the intestines of patients with MHO and MUHO. In obesity, there is an increase in DNA translocation of the genera Rhodococcus, Streptomyces, CF231, Leuconostoc, Burkholderia, Providencia, and Enhydrobacter. Higher blood DNA content of Flavobacterium, Phascolarctobacterium, Kaistobacter, Comamonas, and Enhydrobacter was a feature of patients with MHO. In MUHO, translocation of Prevotella, Blautia, Coprococcus, Ruminococcus, Paracoccus, and Pseudomonas DNA into the blood was increased. In patients with MHO, a positive effect of intestinal kynurenine on the diversity of bacterial DNA in the blood was observed, whereas the concentration of 5-hydroxyindole-3-acetate in feces in MUHO was negatively associated with the diversity characteristics. Conclusions. The content of tryptophan metabolites in feces correlates with the presence of DNA of various taxa in the blood both negatively and positively, which indicates their role in regulating bacterial DNA translocation from the intestine.

众所周知,肥胖会改变肠壁的通透性,包括细菌DNA的通透性。因此,肥胖患者与健康个体在血液中细菌DNA的含量和微生物代谢物方面都有所不同。吲哚代谢物是肠道菌群转化色氨酸的特定产物。一些吲哚参与调节紧密连接蛋白的表达,因此对肠通透性的调节很重要。我们的研究目的是探讨粪便中色氨酸代谢物的含量与血液中细菌DNA水平之间的关系。材料和方法。该研究包括没有肥胖的健康供体(n = 138)和肥胖患者(n = 128),他们被分为代谢健康型肥胖和代谢不健康型肥胖两组。从静脉血样本中分离细菌DNA,对16S rRNA基因v3-v4可变区进行宏基因组测序。比较了样本中单个分类群的分离频率和这些分类群在血液中细菌DNA总库中的份额。采用高效液相色谱-质谱法测定粪便提取物中色氨酸代谢物的浓度。采用Discovery PFP HS分析柱进行色谱分离;采用基于Agilent 6470 MRM三重四极杆电喷雾电离的质谱检测器进行检测。结果。在MHO和MUHO患者的肠道中,色氨酸分解代谢的犬尿氨酸和吲哚途径的代谢物含量也出现了类似的减少。在肥胖人群中,红球菌属、链霉菌属、CF231属、白菌属、伯克霍尔德氏菌属、普罗维登氏菌属和Enhydrobacter属的DNA易位增加。黄杆菌、Phascolarctobacterium、Kaistobacter、Comamonas和Enhydrobacter的血DNA含量较高是MHO患者的特征。在MUHO中,普雷沃氏菌、蓝索菌、粪球菌、瘤胃球菌、副球菌和假单胞菌DNA在血液中的易位增加。在MHO患者中,肠道犬尿氨酸对血液中细菌DNA多样性有积极影响,而MUHO患者粪便中5-羟基吲哚-3-乙酸酯浓度与多样性特征呈负相关。结论。粪便中色氨酸代谢物的含量与血液中各种分类群DNA的存在呈负相关和正相关,这表明它们在调节细菌DNA从肠道转运中的作用。
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引用次数: 0
Geodorum densiflorum Rhizome Lectin Induces Apoptosis in Human Lung Cancer Cells and Inhibits the Growth of Ehrlich Ascites Carcinoma Cells In Vivo in Mice 密花蒿凝集素诱导人肺癌细胞凋亡及抑制小鼠体内埃利希腹水癌细胞生长
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750825600116
Mizanur R. Mamun, Syed R. Kabir, Imtiaj Hasan, A. K. M. Asaduzzaman, Mohammad T. Alam

Geodoram densiflorum or pink nodding orchid grows in wet habitats in Bangladesh. Rural people traditionally use this orchid’s pseudobulbs to treat skin inflammation, tumors and carbuncles. Though a protein from these bulbs previously showed antitumor activity against Ehrlich ascites carcinoma (EAC) cells in vitro, this study focused on proving this effect in vivo in a mice model and against a human cancer cell line. GDL exhibited around 45% growth inhibition against A549 cells at a concentration of 64 µg/mL implicating a caspase-dependent pathway modulated by caspase-3, -8, and -9 inhibitors. The condensed nuclei and morphological changes of GDL-treated cells indicating apoptosis also became evident by Hoechst 33342 and FITC-annexin V/PI staining. GDL up-regulated CASP9 and p53 while down-regulating PARP, MAPK, and STAT3 gene expression, suggesting the involvement of death receptor and intrinsic mitochondrial pathways. Flow cytometry analysis revealed GDL-induced G0/G1 phase cell cycle arrest. In vivo, GDL inhibited EAC cell proliferation by 48%, extending EAC-bearing mice lifespan by 37.05%, and improved hematological parameters, notably increasing red blood cell counts and hemoglobin levels to 2.41 × 109 RBC/mL and 10.27 g/dL, respectively. These findings underscore the therapeutic potential of GDL, setting the stage for further in-depth research.

粉红点头兰生长在孟加拉国潮湿的栖息地。农村居民传统上使用这种兰花的假球茎来治疗皮肤炎症、肿瘤和痈。尽管来自这些球囊的蛋白质先前在体外显示出对埃利希腹水癌(EAC)细胞的抗肿瘤活性,但这项研究的重点是在小鼠模型和人类癌细胞系中证明这种作用。当浓度为64 μ g/mL时,GDL对A549细胞的生长抑制作用约为45%,这暗示了caspase依赖性途径由caspase-3、-8和-9抑制剂调节。Hoechst 33342染色和FITC-annexin V/PI染色显示,gdl处理的细胞细胞核浓缩,形态学变化表明细胞凋亡。GDL上调CASP9和p53,下调PARP、MAPK和STAT3基因表达,提示死亡受体和线粒体内在通路参与其中。流式细胞术分析显示gdl诱导的G0/G1期细胞周期阻滞。体内,GDL抑制EAC细胞增殖48%,延长EAC小鼠寿命37.05%,改善血液学参数,红细胞计数和血红蛋白水平显著增加,分别达到2.41 × 109 RBC/mL和10.27 g/dL。这些发现强调了GDL的治疗潜力,为进一步深入研究奠定了基础。
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引用次数: 0
Evaluation of Ornithine Decarboxylase and Ferric Reducing Capacity Levels as Potential Biomarkers for Polycystic Ovary Syndrome 评价鸟氨酸脱羧酶和铁还原能力水平作为多囊卵巢综合征的潜在生物标志物
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-21 DOI: 10.1134/S1990750825600220
Noor Jasim Mohamed,  Ali Waleed Al-Ani

Background: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder affecting reproductive-age women, often linked to metabolic issues like insulin resistance. Objective: this study aimed to evaluate ornithine decarboxylase (ODC) and ferric reducing capacity (FRC) levels in women with PCOS, with assess the effects of metformin and Primolut N treatment on their levels. Subjects and Methods: A case−control study was conducted with 150 married Iraqi women, categorized into three groups: 50 healthy controls, 50 untreated PCOS, 50 treated PCOS. Blood samples were analyzed for ODC, FRC levels and hormonal profiles. Statistical analysis applied independent t-test, Pearson’s correlation, ROC curve. Results: The ODC level was significantly increased while the FRC level was substantially decreased in PCOS patients compared to controls. Under metformin and Primolut N treatment, both ODC and FRC concentrations were improved to be close to their levels in control group. This reveals the potential role of ODC and FRC in PCOS progression. ROC results showed perfect sensitivity and specificity of ODC and FRC in PCOS diagnosing. Conclusions: The study introduces ODC and FRC as a valuable biomarker for diagnosing PCOS, highlighting its role in the disorder’s pathophysiology.

背景:多囊卵巢综合征(PCOS)是一种影响育龄妇女的普遍激素失调,通常与胰岛素抵抗等代谢问题有关。目的:本研究旨在评估PCOS女性鸟氨酸脱羧酶(ODC)和铁还原能力(FRC)水平,并评估二甲双胍和Primolut N治疗对其水平的影响。研究对象和方法:对150名已婚伊拉克妇女进行病例对照研究,将其分为三组:50名健康对照组,50名未治疗多囊卵巢综合征,50名治疗多囊卵巢综合征。对血液样本进行ODC、FRC水平和激素谱分析。统计分析采用独立t检验、Pearson相关、ROC曲线。结果:与对照组相比,PCOS患者ODC水平显著升高,FRC水平显著降低。在二甲双胍和Primolut N处理下,ODC和FRC浓度均提高至接近对照组水平。这揭示了ODC和FRC在PCOS进展中的潜在作用。ROC结果显示,ODC和FRC对PCOS诊断具有良好的敏感性和特异性。结论:本研究引入了ODC和FRC作为诊断PCOS的有价值的生物标志物,强调了其在PCOS病理生理中的作用。
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引用次数: 0
Variability in the Content of 8-Hydroxy-2-deoxyguanosine as a Marker of Oxidative Stress during Subchronic Intoxication with Pesticides 8-羟基-2-脱氧鸟苷含量的变异性作为亚慢性农药中毒时氧化应激的标志
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-15 DOI: 10.1134/S1990750824601000
V. A. Korolev, L. A. Babkina, E. V. Felker, L. A. Yachmeneva, R. Yu. Chertova, M. A. Usachev, A. I. Milova

In this study, a change in the concentration of 8-hydroxy-2-deoxyguanosine (8-OHdG) in the oral fluid and plasma of model animals (rats) during subchronic intoxication with different classes of pesticides (thiram and imidacloprid) was studied. The intake of pesticides into the organism of rats with standard feed or water at a dose of 1/50 LD50 for 28 days is accompanied by the production of an excess amount of reactive oxygen species (ROS) in the oral fluid and plasma. A cessation in pesticide intake leads to an insignificant decrease in ROS but does not reach the level of intact animals. An increase in the amount of 8-OHdG during subchronic intoxication with pesticides indicates the oxidative damage to DNA. In the oral fluid, the effect of thiram is accompanied by an increase in the amount of 8-OHdG on the day 21 of intoxication and in plasma at the day 7; at the same time, the level of 8-OHdG after the cessation of intoxication decreases to the control in the oral fluid and remains excessive in plasma. Imidacloprid leads to a growth in 8-OHdG in the oral fluid and plasma during 28 days of intoxication. After the cessation of the intake after 28 days, an increased content of 8-OHdG in the oral fluid and plasma remains. Imidacloprid causes a more pronounced oxidative effect on DNA as compared with thiram, which is accompanied by higher concentrations of 8‑OHdG in biological fluids. The accumulation of 8-OHdG indicates a depletion of antioxidant and reparative systems of the organism.

本研究研究了模型动物(大鼠)亚慢性中毒时口服液和血浆中8-羟基-2-脱氧鸟苷(8-OHdG)浓度的变化。用标准饲料或水以1/50 LD50的剂量将农药摄入大鼠体内28天,同时在口服液和血浆中产生过量的活性氧(ROS)。停止摄入农药会导致ROS的显著下降,但不会达到正常动物的水平。亚慢性农药中毒期间8-OHdG含量的增加表明DNA受到氧化损伤。在口服液中,thiram的作用伴随着中毒第21天和第7天血浆中8-OHdG量的增加;同时,停止中毒后口服液中8-OHdG水平降至控制水平,血浆中8-OHdG水平仍然过高。吡虫啉导致28天中毒期间口服液和血浆中8-OHdG的增长。停药28天后,口服液和血浆中8-OHdG含量仍然升高。与噻美姆相比,吡虫啉对DNA的氧化作用更明显,这伴随着生物体液中更高浓度的8 - OHdG。8-OHdG的积累表明机体抗氧化和修复系统的衰竭。
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引用次数: 0
Cj0983 and Cj0090 Lipoproteins Contain Potential Linear Peptide Epitopes for Anti-Campylobacter jejuni Vaccine Applications Cj0983和Cj0090脂蛋白含有抗空肠弯曲杆菌疫苗应用的潜在线性肽表位
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-15 DOI: 10.1134/S1990750824600821
Jamai Pruline D. Sale, Monique M. Oro, Bennies T. Agnazata, Nedrick T. Distor

Campylobacter jejuni, a Gram-negative bacterium, is the major etiologic agent of campylobacteriosis responsible for approximately 90% of reported foodborne infections globally. As a result, alternative approaches such as bacterial vaccines may play pivotal roles in mitigating these bacterial public health concerns. Although there are ongoing studies on the development of vaccine candidates based on antigenic molecules of C. jejuni, the potential of Cj0983 and Cj0090 to be independently considered in the preparation of a protective lipoprotein antigen-based anti-C. jejuni vaccine remains elusive. Herein, the potential linear antigenic epitopes in Cj0983 and Cj0090 from C. jejuni were investigated for possible vaccine applications. Linear peptide epitopes were identified and evaluated for their antigenic and non-allergenic properties using VaxiJen and AllergenFP, respectively. Comprehensive bioinformatics-based in silico analyses revealed that there were 37 B-cell, 371 Class I T-cell, and 365 Class II T-cell peptide epitopes found in Cj0983. In comparison, there were 10 B-cell, 63 Class I T-cell, and 93 Class II T-cell peptide epitopes found in Cj0090. Through PyMOL, selected molecular interactions were screened and predicted between chains of human leukocyte antigen (HLA)-peptide epitope complexes, revealing that H-bonding is the predominant intermolecular force during binding. Our results identified the top three peptide epitopes for Cj0983 (312QNDDYKLNLDLKFKN326, 311TQNDDYKLNLDLKFK325, and 309NITQNDDYKLNLDLKF324) and Cj0090 (98QEVILRKLASDTRAND113, 106ASDTRANDFRLEIKA120, and 113DFRLEIKAK121) which have great potentials as vaccine components and can further be utilized as contributing protein-derived molecules towards advancing anti-C. jejuni vaccine development.

空肠弯曲杆菌是一种革兰氏阴性菌,是弯曲杆菌病的主要病原,全球约90%的食源性感染报告由弯曲杆菌引起。因此,细菌疫苗等替代方法可能在减轻这些细菌公共卫生问题方面发挥关键作用。虽然目前正在进行基于空肠梭菌抗原分子的候选疫苗开发研究,但在制备保护性的基于脂蛋白抗原的抗c抗体时,需要单独考虑Cj0983和Cj0090的潜力。空肠疫苗仍然难以捉摸。本文对空肠梭菌Cj0983和Cj0090的潜在线性抗原表位进行了研究,以期应用于疫苗。利用VaxiJen和AllergenFP分别鉴定和评价线性肽表位的抗原性和非致敏性。基于计算机生物信息学的综合分析显示,在Cj0983中发现37个b细胞、371个I类t细胞和365个II类t细胞肽表位。相比之下,在Cj0090中发现10个b细胞、63个I类t细胞和93个II类t细胞肽表位。通过PyMOL,筛选和预测了人类白细胞抗原(HLA)-肽表位复合物链之间的分子相互作用,揭示了h键是结合过程中主要的分子间作用力。我们的研究结果确定了Cj0983的前三个肽表位(312QNDDYKLNLDLKFKN326、311TQNDDYKLNLDLKFK325和309nitqnddyklnldllkf324)和Cj0090 (98QEVILRKLASDTRAND113、106ASDTRANDFRLEIKA120和113DFRLEIKAK121),它们具有很大的潜力作为疫苗成分,可以进一步利用作为促进抗c的蛋白源性分子。空肠疫苗开发。
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引用次数: 0
Thermodynamic and Electrochemical Characteristics of Urine Protein Molecules That Affect the Formation of Stones 影响结石形成的尿蛋白分子的热力学和电化学特性
IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-15 DOI: 10.1134/S1990750824601346
A. S. Tatevosyan, A. V. Bunyakin, S. N. Alekseenko, Z. O. Katani
<p>Pathogenetic development of urolithiasis (UL) can be divided chronologically into prestone phase and stone phase. Specifically, the stone phase (SP) occurs from the moment when Randall plaque (RP), which is calcium phosphate (CaP) in 100% of cases, having destroyed the epithelial layer of the papilla in the renal calyx, comes into direct contact with urine, which is saturated not only with numerous inorganic microelements but also with various organic molecules, which always leave “traces of protein.” The study of the composition of the stone shows that, in addition to inorganic substances, there is always a protein component, the role of which has not yet been fully disclosed. The most unclear question remains why urinary proteins (uromodulin, osteopontin…) are able to both inhibit stone growth and act as promoters of stone formation. No less intriguing is the question of why calcium oxalate (CaOx) is the most common calculus in the urinary system. Objective. To determine the features of thermodynamic (TD) and electrochemical (EC) mechanisms that promote the growth of urinary calculus on the calcium phosphate (CaP) template already formed in the renal papilla in the form of RP and to establish the role of the protein (organic) component in this process as well as to find out the reasons why CaOx is the most common calculus in the urinary system. Materials and methods. A metaanalysis of TD and EC mechanisms promoting the growth of urinary calculus on the already formed CaP “seed” in the form of RP was performed, and the effect of the isoelectric point (pI) of proteins deposited on this CaP template was determined. Considering that CaOx stones are the most common (60–80%), the рI of urinary protein molecules affecting their growth was compared with the features of circadian urine pH fluctuations. An analogy of the adhesive theory of electrical and electron formation of complex compounds that determine metal−ligand homeostasis is presented. Results and discussion. Proteins (peptides, amino acids) are weak electrochemical molecules, on the outer surface of which (depending on the pH of the external environment) a cationic or anionic charge prevails. An individual feature of any protein is its specific рI, in which the protein loses its EC activity and precipitates. Subsequently, the corresponding inorganic substances floating in the urine settle on the already aggregated protein layer. As a rule, рI of any protein is located within narrow limits of pH fluctuations not exceeding 1 unit (∆рН < 1), while, for the aggregation of the protein, in addition to its stay in рI, time is needed, which determines the rate; i.e., a long stay of the protein in pI is necessary for the formation of an organic layer on the RP. The range of physiological fluctuations in urine pH during the day varies from 5.0 to 8.0 (∆pH ≈ 3). Obviously, with such a 1000-fold range of proton (H<sup>+</sup>) oscillations, none of the proteins present in the urine have time to agg
尿石症的发病发展可按时间顺序分为结石前期和结石期。具体来说,结石期(SP)发生在兰德尔斑块(RP),即100%的磷酸钙(CaP),破坏了肾盂乳头的上皮层,与尿液直接接触的那一刻,尿液不仅饱和了大量的无机微量元素,还饱和了各种有机分子,这些分子总是留下“蛋白质的痕迹”。对石材组成的研究表明,除了无机物外,始终存在一种蛋白质成分,其作用尚未完全揭示。最不清楚的问题仍然是为什么尿蛋白(尿调节蛋白、骨桥蛋白等)既能抑制结石生长,又能促进结石形成。同样有趣的是,为什么草酸钙(CaOx)是泌尿系统中最常见的结石。目标。确定在肾乳头内以RP形式形成的磷酸钙(CaP)模板上促进尿结石生长的热力学(TD)和电化学(EC)机制的特点,确定蛋白质(有机)成分在这一过程中的作用,并找出CaOx是泌尿系统中最常见的结石的原因。材料和方法。我们对TD和EC在已经形成的RP形式的CaP“种子”上促进尿结石生长的机制进行了荟萃分析,并确定了沉积在该CaP模板上的蛋白质的等电点(pI)的影响。考虑到CaOx结石最为常见(60-80%),我们将尿蛋白分子对其生长的影响与尿pH昼夜波动的特征进行比较。一个类比的电和电子形成的复杂化合物的粘合理论,确定金属-配体稳态提出。结果和讨论。蛋白质(多肽、氨基酸)是弱电化学分子,其外表面(取决于外部环境的pH值)以阳离子或阴离子电荷为主。任何蛋白质的一个单独的特征是它的特异性,其中蛋白质失去其EC活性和沉淀。随后,尿液中相应的无机物漂浮在已经聚集的蛋白质层上。通常,任何蛋白质的 <; 1都位于pH波动不超过1个单位的狭窄范围内(∆рН < 1),而对于蛋白质的聚集,除了停留在 <; 1中外,还需要时间,这决定了速度;也就是说,蛋白质在pI中的长时间停留对于RP上有机层的形成是必要的。白天尿液pH值生理波动范围为5.0 ~ 8.0(∆pH≈3)。显然,在质子(H+)振荡的1000倍范围内,尿液中存在的蛋白质没有时间聚集,因此,尿液的整个胶体晶体系统处于溶解状态。在那些病理病例中,当尿液pH值长时间(10-15天)在狭窄的范围内,不超过1(等酸尿症),可能是一些蛋白质(其pI在这些特定范围内)失去其活性(溶解度)并沉淀在RP上,形成有机层。一层假体金属离子和各种酸盐(通常是草酰乙酸…),存在于尿液中,然后在这种蛋白质基质的表面形成。根据高斯-拉普拉斯定律,尿液pH值的日波动分布不均匀(≠恒定),最常见(60-80%)的值位于6.0 - 7.0(∆pH < 1)之间。初期尿石症(包括肾小管酸中毒)患者的尿液pH值也在微酸性范围内,主要是对于CaOx结石,发现pI正好在这个范围内(6.0 ~ 7.0)的尿蛋白具有高可靠性(p = 0.04)!这解释了一个众所周知的事实,即在60-80%的尿石症病例中,发现了这种特殊类型的结石,CaOx。结论。在尿石症期间,在乳头顶端形成的RP与尿液无阻碍接触,并作为结石进一步生长的模板,位于等电点(pI)的蛋白质聚集过程开始发挥主要作用,这种聚集过程对每种特定蛋白质来说都是个体的。由于pI对所有蛋白质分子都有自己狭窄的酸度范围(ΔpH < 1),因此,当尿液pH值波动超过两个单位的极限(ΔpH > 2)时,任何蛋白质在RP上的聚集基本上是不可能的,并且,在没有蛋白质层(基质)的情况下,无论盐浓度如何,任何结石(有机矿物基质- oms)后续形成和生长的可能性都被排除了!
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引用次数: 0
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Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry
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