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Maternal and Newborn Blood Aluminum Levels and Neurodevelopment of Infants: Is there a Need for Concern? 孕产妇和新生儿血液中的铝含量与婴儿的神经发育:是否需要关注?
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2021-09-29 DOI: 10.1007/s12291-021-01002-y
Dolat Singh Shekhawat, Pratibha Singh, Vikash Chandra Janu, Praveen Sharma, Kuldeep Singh

Aluminum is a neurotoxic element that enters the human body due to its widespread usage in daily life. It has the potential to affect the neurological development of the fetus and infant adversely. This study aimed to evaluate the relationship between maternal and umbilical cord serum aluminum level and infant neurodevelopment. Over a period of March 2018 to September 2019, we conducted a prospective cohort study; 173 Mother-new-born pairs were enrolled. Aluminum levels were measured using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The correlation with Bayley Scales of Infant Development (BSID) -3rd edition score and maternal and cord serum aluminum were assessed via linear regression model. The mean concentration of maternal and cord serum aluminum was 2.58 ± 1.14 µg/dL and 1.44 ± 0.62 µg/dL, respectively. There was a significant correlation in aluminum level between maternal and umbilical cord serum (Pearson's r = 0.591, p < 0.000). There is no significant correlation between maternal and serum aluminum level, and BSID-3rd edition (cognitive, motor, language, and social-emotion) score at the average age of 6.5 months. In conclusion, maternal and cord serum aluminum levels were significantly correlated but did not correlate with infant neurodevelopment. Thus, low serum aluminum concentration and their association with child neurodevelopment deserve further investigation longitudinally in a large cohort.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-021-01002-y.

铝是一种神经毒性元素,由于在日常生活中的广泛使用而进入人体。它有可能对胎儿和婴儿的神经系统发育产生不利影响。本研究旨在评估母体和脐带血清铝水平与婴儿神经发育之间的关系。在 2018 年 3 月至 2019 年 9 月期间,我们开展了一项前瞻性队列研究;共招募了 173 对母婴。采用电感耦合等离子体光学发射光谱法(ICP-OES)测量铝含量。通过线性回归模型评估了贝利婴儿发展量表(BSID)第 3 版评分与母体和脐带血清铝的相关性。母体和脐带血清铝的平均浓度分别为 2.58 ± 1.14 µg/dL 和 1.44 ± 0.62 µg/dL。在平均 6.5 个月大时,母体和脐带血清中的铝含量存在明显相关性(Pearson's r = 0.591,p rd)。总之,母体和脐带血清铝水平与婴儿的神经发育有显著相关性,但没有相关性。因此,低血清铝浓度及其与儿童神经发育的关系值得在大型队列中进行纵向研究:在线版本包含补充材料,可在 10.1007/s12291-021-01002-y。
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引用次数: 0
Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases. C4b作为症状性RT-PCR阴性Covid-19病例辅助标志物的评价
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-06-20 DOI: 10.1007/s12291-022-01033-z
Bandana Kumari, Krishnan Hajela, Asgar Ali, Abhay Kumar Sharma, Rajesh Kumar Yadav, Alok Ranjan, Rathish Nair, Shreekant Bharti, Satish Dipankar, Prabhat Kumar Singh, Sadhana Sharma

Introduction: Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low.

Methods: Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40); symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA).

Results: C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases.

Conclusions: The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

引言:在这场导致其传播升级的疫情中,检测低病毒载量一直是一项挑战。补体激活与新冠肺炎感染的发病机制有关。因此,对疑似新冠肺炎感染中补体激活的评估可能有助于检测感染并限制假阴性病例,从而限制感染的传播。我们推测,即使在病毒滴度较低的情况下,测量因新冠肺炎的存在而激活的补体系统产生的C4b也可能有助于检测。方法:有症状的RT-PCR阳性患者(例 = 40);症状性RT-PCR阴性患者(n = 35)和无症状RT-PCR阴性对照(n = 40)进行评价。病例和对照组的血浆C5b-9、IL-6、D-二聚体和C1抑制剂(C1-INH)也进行了测量。ELISA试剂盒用于所有测量。使用Stata第12版(Stata Corp.,Texas,USA)进行统计分析。结果:与无症状RT-PCR阴性对照组相比,RT-PCR阳性患者的C4b水平显著升高。RT-PCR阴性但有症状的患者仍显示C4b水平升高。在临界值≥ 116ng/ml,最佳灵敏度和特异性分别为80%和52%,表明其可能用作辅助标记。与对照组相比,病例中发现D-二聚体IL6水平升高,C1-INH水平降低。然而,C5b-9水平在病例中没有显著升高。结论:我们的研究结果表明,血浆C4b可能有助于检测RT-PCR假阴性病例的感染,这些病例因病毒载量低而逃避检测。然而,要证实这一点,还需要进行大规模的研究。补充信息:在线版本包含补充材料,可访问10.1007/s12291-022-1033-z。
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引用次数: 0
Role of Klotho Protein in Neuropsychiatric Disorders: A Narrative Review. Klotho 蛋白在神经精神疾病中的作用:叙述性综述。
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-08-13 DOI: 10.1007/s12291-022-01078-0
Amandeep Birdi, Sojit Tomo, Dharmveer Yadav, Praveen Sharma, Naresh Nebhinani, Prasenjit Mitra, Mithu Banerjee, Purvi Purohit

Neuropsychiatric disorders are comprised of diseases having both the neurological and psychiatric manifestations. The increasing burden of the disease on the population worldwide makes it necessary to adopt measures to decrease the prevalence. The Klotho is a single pass transmembrane protein that decreases with age, has been associated with various pathological diseases, like reduced bone mineral density, cardiac problems and cognitive impairment. However, multiple studies have explored its role in different neuropsychiatric disorders. A comprehensive search was undertaken in the Pubmed database for articles with the keywords "Klotho" and "neuropsychiatric disorders". The available literature, based on the above search strategy, has been compiled in this brief narrative review to describe the emerging role of Klotho in various neuropsychiatric disorders. The Klotho levels were decreased in various neuropsychiatric disorders except for bipolar disorder. A suppressed Klotho protein levels induced oxidative stress and incited pro-inflammatory conditions significantly contributing to the pathophysiology of neuropsychiatric disorder. The increasing evidence of altered Klotho protein levels in cognition-decrement-related disorders warrants its consideration as a biomarker in various neuropsychiatric diseases. However, further evidence is required to understand its role as a therapeutic target.

神经精神疾病包括神经和精神两方面的疾病。这种疾病给全球人口造成的负担日益加重,因此有必要采取措施降低发病率。Klotho 是一种单通道跨膜蛋白,会随着年龄的增长而减少,与多种病理疾病相关,如骨矿物质密度降低、心脏问题和认知障碍。不过,已有多项研究探讨了它在不同神经精神疾病中的作用。我们在 Pubmed 数据库中全面搜索了以 "Klotho "和 "神经精神疾病 "为关键词的文章。根据上述搜索策略,我们将现有文献整理成这篇简短的叙述性综述,以描述 Klotho 在各种神经精神疾病中的新作用。除躁狂症外,各种神经精神疾病中的 Klotho 水平都有所下降。被抑制的 Klotho 蛋白水平会诱发氧化应激和促炎症反应,这在很大程度上导致了神经精神疾病的病理生理学。越来越多的证据表明,Klotho 蛋白水平的改变与认知功能障碍有关,因此有必要将其视为各种神经精神疾病的生物标志物。然而,要了解其作为治疗靶点的作用,还需要进一步的证据。
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引用次数: 4
Extracellular Vesicles (EVs) as "A Window to the Brain": Potential, Challenges and Future Perspectives. 作为 "大脑之窗 "的细胞外囊泡 (EV):潜力、挑战和未来展望。
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-01-09 DOI: 10.1007/s12291-023-01111-w
Prasenjit Mitra, Shruti Gupta, Praveen Sharma
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引用次数: 2
Impact of Covishield Vaccination in Terms of SARS CoV-2 Neutralizing Antibody Expression. 接种covshield对SARS CoV-2中和抗体表达的影响
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.1007/s12291-022-01030-2
Rhema Elizabeth Thomas, Ajaikumar Sukumaran, Arun Krishnan R, Thushara Thomas, Biby T Edwin, P R Haritha, Bilha M Varghese, Jofy K Paul, Satheesh Kumar C S, D M Vasudevan

The vaccination efficacy can indirectly be assessed through the quantification of neutralizing antibodies. Very few data are available on Covishield efficacy in terms of neutralizing antibody expression upon vaccination. This study is focused on profiling of neutralizing antibody expression during and after the Covishield two shot vaccination and observing COVID-19 infection in vaccinated participants during the period. SARS CoV-2 neutralizing antibody concentrations in samples were estimated using electrochemiluminescence immunoassay kit for Lifotronics eCL8000. The sampling had been done sequentially at 45th, 85th day after 1st dose and 15th day after 2nd dose Covishield vaccination. Parallelly, in order to confirm the total SARS CoV-2 IgG response in COVID-19 infection, measured the IgG using SARS CoV-2 IgG lateral flow immunoassay test kit. The subjects previously infected with COVID-19 before 1st dose vaccination demonstrated high neutralizing antibody (> 10AU/ml). In COVID-19 uninfected subjects, there was a sudden incline in neutralizing antibody after the 2nd dose. Infection with SARS CoV-2 between 1st and 2nd dose of Covishield vaccination implicate that the level of neutralizing antibody in serum after 1st dose was not adequate to combat the virus and prevent infection. We observed COVID-19 infection in participants even after 2nd dose of vaccination. Interestingly, there was no protection against SARS CoV-2 even with a high neutralizing antibody expression of 188.5 AU/mL after the 2nd dose. Findings of Covishield efficacy in different cohort samples before and after 2 doses of Covishield vaccination provide impetus for improvement or development of next generation vaccines.

通过中和抗体的定量,可以间接评价疫苗接种效果。在疫苗接种后,很少有数据表明Covishield在中和抗体表达方面的有效性。本研究的重点是分析Covishield两次疫苗接种期间和之后的中和抗体表达,并观察接种参与者在此期间的COVID-19感染情况。使用Lifotronics eCL8000的电化学发光免疫测定试剂盒估计样品中SARS CoV-2中和抗体的浓度。接种第1剂后第45天、第85天、第2剂后第15天依次取样。同时,为了确认COVID-19感染时SARS CoV-2 IgG总应答,采用SARS CoV-2 IgG侧流免疫测定试剂盒检测IgG。首次接种前已感染COVID-19的受试者表现出较高的中和抗体(> 10AU/ml)。在未感染COVID-19的受试者中,第二次注射后,中和抗体出现突然倾斜。在第一次和第二次接种Covishield期间感染SARS CoV-2意味着第一次接种后血清中和抗体水平不足以对抗病毒和预防感染。我们观察到参与者在接种第二剂疫苗后仍有COVID-19感染。有趣的是,即使在第二次剂量后,中和抗体的表达达到188.5 AU/mL,也没有对SARS CoV-2产生保护作用。两剂Covishield疫苗接种前后不同队列样本的有效性研究结果为下一代疫苗的改进或开发提供了动力。
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引用次数: 0
Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study. 易患巨幼红细胞性贫血人群血清全曲钴胺与血清维生素 B12 的比较及其与神经传导研究的相关性。
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-03-17 DOI: 10.1007/s12291-022-01027-x
Abhishek Verma, Sunita Aggarwal, Sandeep Garg, Smita Kaushik, Debashish Chowdhury

Early detection of megaloblastic anemia and associated neurological complications is crucial for management. This study was conducted to compare serum holotranscobalamin level with serum vitamin B12 level as early biomarker in people prone to megaloblastic anemia and to evaluate co-relation between these biomarkers and nerve conduction study in study patients. 83 adult patients (Hb > 12 gm/dl) prone to megaloblastic anemia were studied for basic haematological investigations, random blood sugar, thyroid function test, liver function test, kidney function test, serum vitamin B12, serum holotranscobalamin and serum folic acid levels. 45 patients among them underwent nerve conduction studies. All study patients were classified in 6 groups on the basis of risk factors for megaloblastic anemia. 29 patients (34.9%) were on antiepileptic drugs, 26 (31.3%) were chronic alcoholic, 10 patients (12%) each, had malabsorption and ileal tuberculosis, 6 (7.22%) had chronic pancreatitis and 2 (2.4%) had ileal resection. 30 patients (36.14%) had low serum holotranscobalamin, including 7 patients (8.43%) with low serum vitamin B12 level also, unmasking vitamin B12 deficiency in 23 patients (27.7%). 7 patients (8.43%) had mean corpuscular volume (MCV) > 100fL and 8 patients (9.63%) had vitamin B12 deficiency related changes on peripheral smear. Serum vitamin B12 and holotranscobalamin levels were significantly low in patients with peripheral smear changes, with p value 0.039 and 0.041 respectively, while no such association seen with MCV. Subclinical peripheral neuropathy was detected in 18 (40%) out of 45 patients on nerve conduction study. Serum holotranscobalamin levels were significantly lower (p = 0.031) than serum vitamin B12 levels (p = 0.2) in patients with neuropathic changes. Rest investigations and serum folic acid levels were normal in all patients. Holotranscobalamin levels can be considered early and reliable marker for vitamin B12 deficiency and deficiency associated peripheral neuropathy, even in patients who are prone to megaloblastic anemia, and not yet anemic or symptomatic for neuropathy.

早期发现巨幼细胞性贫血及相关神经系统并发症对于治疗至关重要。本研究旨在比较血清全转铁蛋白水平和血清维生素 B12 水平作为巨幼细胞性贫血患者的早期生物标志物,并评估这些生物标志物与患者神经传导研究之间的相关性。研究人员对 83 名易患巨幼细胞性贫血的成年患者(血红蛋白大于 12 克/分升)进行了基本血液学检查、随机血糖、甲状腺功能检测、肝功能检测、肾功能检测、血清维生素 B12、血清全转铁蛋白和血清叶酸水平检测。其中 45 名患者接受了神经传导检查。根据巨幼细胞贫血的风险因素,所有研究对象被分为 6 组。29名患者(34.9%)服用过抗癫痫药物,26名患者(31.3%)长期酗酒,10名患者(12%)患有吸收不良和回肠结核,6名患者(7.22%)患有慢性胰腺炎,2名患者(2.4%)进行过回肠切除术。30 名患者(36.14%)的血清全转录钴胺素水平较低,其中 7 名患者(8.43%)的血清维生素 B12 水平也较低,23 名患者(27.7%)的维生素 B12 缺乏。7 名患者(8.43%)的平均血球容积(MCV)大于 100fL,8 名患者(9.63%)的外周涂片出现与维生素 B12 缺乏相关的变化。有外周涂片变化的患者血清维生素 B12 和全血钴胺素水平明显偏低,P 值分别为 0.039 和 0.041,而 MCV 与维生素 B12 缺乏症无关联。45 名患者中有 18 人(40%)在神经传导检查中发现了亚临床周围神经病变。在有神经病变的患者中,血清全曲钴胺素水平(p = 0.031)明显低于血清维生素 B12 水平(p = 0.2)。所有患者的其他检查和血清叶酸水平均正常。即使是易患巨幼红细胞性贫血、尚未贫血或没有神经病变症状的患者,全血钴胺水平也可被视为维生素 B12 缺乏症和缺乏症相关周围神经病变的早期可靠标志物。
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引用次数: 0
Study of MicroRNA (miR-221-3p, miR-133a-3p, and miR-9-5p) Expressions in Oral Submucous Fibrosis and Squamous Cell Carcinoma. 口腔黏膜下纤维化和鳞状细胞癌中的微RNA(miR-221-3p、miR-133a-3p 和 miR-9-5p)表达研究
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-04-29 DOI: 10.1007/s12291-022-01035-x
Shweta Ukey, Ankit Jain, Shailendra Dwivedi, Chinmayee Choudhury, Jeewan Ram Vishnoi, Ankita Chugh, Purvi Purohit, Puneet Pareek, Poonam Elhence, Sanjeev Misra, Praveen Sharma

Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Epigenetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening. The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. In the present study, the expression of these miRNAs was examined in 34 histopathologically confirmed OSCC, 30 OSMF, and 29 control (healthy volunteers) human samples. There was a significant downregulation of miRNA-133a-3p in OSCC compared to OSMF and controls, whereas there was up-regulation in oral submucous fibrosis compared to controls. There was no significant difference in the expression of miR-221-3p between OSCC and OSMF, but an upregulation in OSCC compared to controls. miR-9-5p was also found upregulated in both OSCC and OSMF. Further, miR-133a-3p expression was negatively correlated with age, smoking, drinking status, and AJCC staging, whereas miR-9-5p expression was only positively associated with tobacco/ areca nut chewing. The ROC plots, logistic regression model generated, and the correlation between the expression of miR-9-5p and miR-133a-3p in blood and tissue suggests that these could be used as risk stratification biomarkers.

口腔鳞状细胞癌(OSCC)是常见的癌症类型之一。它的发病过程是从口腔潜在恶性疾病(OPMD)(如口腔黏膜下纤维化(OSMF))过渡而来。表观遗传修饰因子,尤其是微小核糖核酸(miRNA),在各种致癌途径的调控中发挥着重要作用,被用作生物标志物。在文献检索中发现,miR-221-3p、miR133a-3p 和 miR-9-5p 这三种 miRNA 在许多癌症中都有不同程度的表达。文献和我们在早期研究中进行的功能富集分析表明,这些 miRNA 可在不同阶段调控癌变。本研究检测了 34 例经组织病理学证实的 OSCC、30 例 OSMF 和 29 例对照组(健康志愿者)人体样本中这些 miRNA 的表达。与 OSMF 和对照组相比,miRNA-133a-3p 在 OSCC 中明显下调,而与对照组相比,miRNA-133a-3p 在口腔黏膜下纤维化中上调。在 OSCC 和 OSMF 中,miR-221-3p 的表达没有明显差异,但与对照组相比,OSCC 中的 miR-221-3p 表达上调。此外,miR-133a-3p 的表达与年龄、吸烟、饮酒状况和 AJCC 分期呈负相关,而 miR-9-5p 的表达仅与咀嚼烟草/山苍子呈正相关。ROC图、逻辑回归模型的生成以及血液和组织中miR-9-5p和miR-133a-3p表达量之间的相关性表明,这些指标可用作风险分层生物标志物。
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引用次数: 3
Glutamine-Driven Metabolic Adaptation to COVID-19 Infection. 谷氨酰胺驱动的COVID-19感染代谢适应
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.1007/s12291-022-01037-9
Hüseyin Aydın, Yusuf Kenan Tekin, İlhan Korkmaz, Gülaçan Tekin, Sefa Yurtbay, Sami Keleş, Nezih Hekim

Background: COVID-19 is known to be transmitted by direct contact, droplets or feces/orally. There are many factors which determines the clinical progression of the disease. Aminoacid disturbance in viral disease is shown in many studies. İn this study we aimed to evaluate the change of aminoacid metabolism especially the aspartate, glutamine and glycine levels which have been associated with an immune defence effect in viral disease.

Methods: Blood samples from 35 volunteer patients with COVID-19, concretized diagnosis was made by oropharyngeal from nazofaringeal swab specimens and reverse transcriptase-polymerase chain reaction, and 35 control group were analyzed. The amino acid levels were measured with liquid chromatography-mass spectrometry technology. Two groups were compared by Kolmogorov-Smirnov analysis, Kruskal-Wallis and the Mann-Whitney U. The square test was used to evaluate the tests obtained by counting, and the error level was taken as 0.05.

Results: The average age of the patient and control group were 48.5 ± 14.9 and 48.8 ± 14.6 years respectively. The decrease in aspartate (p = 5.5 × 10-9) and glutamine levels (p = 9.0 × 10-17) were significiantly in COVID group, whereas Glycine (p = 0.243) increase was not significiant.

Conclusions: Metabolic pathways, are affected in rapidly dividing cells in viral diseases which are important for immun defence. We determined that aspartate, glutamine and glycine levels in Covid 19 patients were affected by the warburg effect, malate aspartate shuttle, glutaminolysis and pentose phosphate pathway. Enteral or parenteral administration of these plasma amino acid levels will correct the duration and pathophysiology of the patients' stay in hospital and intensive care.

背景:已知COVID-19通过直接接触、飞沫或粪便/口服传播。有许多因素决定疾病的临床进展。许多研究表明病毒性疾病中存在氨基酸紊乱。İn本研究旨在评估在病毒性疾病中与免疫防御作用相关的氨基酸代谢,特别是天冬氨酸、谷氨酰胺和甘氨酸水平的变化。方法:对35例自愿感染COVID-19的患者进行血液采集,经口咽咽咽拭子标本和逆转录-聚合酶链反应进行具体诊断,并对35例对照组进行分析。采用液相色谱-质谱联用技术测定氨基酸水平。两组比较采用Kolmogorov-Smirnov分析、Kruskal-Wallis分析和Mann-Whitney U.检验,计数所得检验采用平方检验,误差水平取0.05。结果:患者和对照组的平均年龄分别为48.5±14.9岁和48.8±14.6岁。COVID组天冬氨酸水平(p = 5.5 × 10-9)和谷氨酰胺水平(p = 9.0 × 10-17)显著降低,甘氨酸水平(p = 0.243)升高不显著。结论:在病毒性疾病中,代谢途径在细胞快速分裂过程中受到影响,在免疫防御中起重要作用。我们发现,新冠肺炎患者体内天冬氨酸、谷氨酰胺和甘氨酸水平受warburg效应、苹果酸-天冬氨酸穿梭、谷氨酰胺水解和戊糖磷酸途径的影响。这些血浆氨基酸水平的肠内或肠外管理将纠正患者住院和重症监护的时间和病理生理。
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引用次数: 3
Identification of Plasma Proteomic Biomarkers in Patients with Mild Cognitive Impairment. 鉴定轻度认知障碍患者的血浆蛋白质组生物标志物
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-02-15 DOI: 10.1007/s12291-022-01023-1
Vineeta Singh, Vijaya Nath Mishra, Mahendra Kumar Thakur

Plasma proteomic profiling may provide novel biomarkers for the identification of mild cognitive impairment (MCI). The early diagnosis of MCI still remains a challenging task due to its diverse origin. Currently, molecular approaches have been used to identify MCI diversified origin as its onset is governed by a variety of molecular changes. Therefore, we aimed to find out molecular alteration in plasma using proteomics in patients with MCI for early detection of prodromal Alzheimer's disease (AD). To achieve this, we performed two-dimensional (2-D) gel electrophoresis coupled with MALDI-TOF/MS, which is used to analyze the differentially expressed proteins. In our study, we found three significantly altered proteins. Out of three differentially expressed proteins, one was downregulated and two were upregulated in MCI individuals as compared to control. Further, In silico analysis showed that identified proteins are involved in pathways such as complement and coagulation cascades, platelet activation and AD. STRING interaction network analysis revealed that the majority of proteins including apolipoprotein E (APO-E) have a common association with Transthyretin (TTR) and fibrinogen chain beta (FGB) protein. This suggests that APO-E, TTR and FGB are the key proteins with which other proteins interact to exert other biological functions. Conclusively, these proteins showing differential expression in the plasma might be used as a potent signature in blood for the diagnosis of MCI individuals.

血浆蛋白质组分析可为轻度认知障碍(MCI)的鉴定提供新的生物标志物。由于MCI的发病原因多种多样,因此早期诊断MCI仍然是一项具有挑战性的任务。目前,由于 MCI 的发病受多种分子变化的影响,分子方法已被用于识别 MCI 的不同起源。因此,我们的目的是利用蛋白质组学发现 MCI 患者血浆中的分子变化,以便早期发现阿尔茨海默病(AD)的前兆。为此,我们进行了二维(2-D)凝胶电泳并结合 MALDI-TOF/MS,用于分析差异表达的蛋白质。在我们的研究中,我们发现了三种明显改变的蛋白质。在三种差异表达的蛋白质中,与对照组相比,MCI 患者的一种蛋白质下调,两种蛋白质上调。此外,硅学分析表明,确定的蛋白质参与了补体和凝血级联、血小板活化和 AD 等通路。STRING相互作用网络分析显示,包括载脂蛋白E(APO-E)在内的大多数蛋白质与转甲状腺素(TTR)和纤维蛋白原链β(FGB)蛋白有共同的关联。这表明,APO-E、TTR 和 FGB 是与其他蛋白质相互作用以发挥其他生物功能的关键蛋白质。最后,这些在血浆中呈现差异表达的蛋白质可作为诊断 MCI 患者的有效血液特征。
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引用次数: 0
Identification of h-TERT Promoter Mutations in Germline DNA from North Indian Lung Carcinoma Patients. 北印度肺癌患者种系 DNA 中 h-TERT 启动子突变的鉴定
IF 2.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-05-19 DOI: 10.1007/s12291-022-01047-7
Rajendra Prasad, Sonia Panchal, Isha Rani, Jai Kishan, Gaurav Parashar

Lung cancer is a severe and the leading cause of cancer related deaths worldwide. The recurrent h-TERT promoter mutations have been implicated in various cancer types. Thus, the present study is extended to analyze h-TERT promoter mutations from the North Indian lung carcinoma patients. Total 20 histopathologically and clinically confirmed cases of lung cancer were enrolled in this study. The genomic DNA was extracted from venous blood and subjected to amplification using appropriate h-TERT promoter primers. Amplified PCR products were subjected for DNA Sanger sequencing for the identification of novel h-TERT mutations. Further, these identified h-TERT promoter mutations were analysed for the prediction of pathophysiological consequences using bioinformatics tools such as Tfsitescan and CIIDER. The average age of patients was 45 ± 8 years which was categorized in early onset of lung cancer with predominance of male patients by 5.6 fold. Interestingly, h-TERT promoter mutations were observed highly frequent in lung cancer. Identified mutations include c. G272A, c. T122A, c. C150A, c. 123 del C, c. C123T, c. G105A, c. 107 Ins A, c. 276 del C corresponding to -168 G>A, -18 T>A, -46 C>A, -19 del C, -19 C>T, -1 G>A, -3 Ins A, -172 del C respectively from the translation start site in the promoter of the telomerase reverse transcriptase gene which are the first time reported in germline genome from lung cancer. Strikingly, c. -18 T>A [C.T122A] was found the most prevalent variant with 75% frequency. Notwithstanding, other mutations viz c. -G168A [c. G272A] and c. -1 G>A [c. G105A] were found to be at 35% and 15% frequency respectively whilst the rest of the mutations were present at 10% and 5% frequency. Additionally, bioinformatics analysis revealed that these mutations can lead to either loss or gain of various transcription factor binding sites in the h-TERT promoter region. Henceforth, these mutations may play a pivotal role in h-TERT gene expression. Taken together, these identified novel promoter mutations may alter the epigenetics and subsequently various transcription factor binding sites which are of great functional significance. Thereby, it is plausible that these germline mutations may involve either as predisposing factor or direct participation in the pathophysiology of lung cancer through entangled molecular mechanisms.

肺癌是一种严重的癌症,也是全球癌症相关死亡的主要原因。反复出现的 h-TERT 启动子突变与多种癌症类型都有关联。因此,本研究扩展分析了北印度肺癌患者的 h-TERT 启动子突变。共有 20 例经组织病理学和临床确诊的肺癌患者参与了本研究。从静脉血中提取基因组 DNA,并使用适当的 h-TERT 启动子引物进行扩增。扩增的 PCR 产物经 DNA Sanger 测序,以鉴定新型 h-TERT 基因突变。此外,还使用 Tfsitescan 和 CIIDER 等生物信息学工具对这些已确定的 h-TERT 启动子突变进行分析,以预测其病理生理后果。患者的平均年龄为 45 ± 8 岁,属于早发性肺癌,男性患者占多数,比例为 5.6 倍。有趣的是,h-TERT 启动子突变在肺癌中非常常见。已发现的突变包括 c. G272A、c. T122A、c. C150A、c. 123 del C、c. C123T、c. G105A、c. 107 Ins A、c.276 del C,分别对应于端粒酶反转录酶基因启动子翻译起始位点的-168 G>A、-18 T>A、-46 C>A、-19 del C、-19 C>T、-1 G>A、-3 Ins A、-172 del C,这在肺癌种系基因组中是首次报道。引人注目的是,c. -18 T>A [C.T122A]是最常见的变异,频率为75%。G168A [c. G272A]和 c. -1 G>A [c. G105A]的频率分别为35%和15%,而其他变异的频率分别为10%和5%。此外,生物信息学分析表明,这些突变可导致 h-TERT 启动子区域中各种转录因子结合位点的缺失或增益。因此,这些突变可能在h-TERT基因表达中起着关键作用。综上所述,这些已发现的新型启动子突变可能会改变表观遗传学,进而改变具有重要功能意义的各种转录因子结合位点。因此,这些种系突变可能是肺癌的易感因素,也可能通过纠缠不清的分子机制直接参与肺癌的病理生理学。
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Indian Journal of Clinical Biochemistry
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