Fluid Protein Research Articles

273. Neurological Involvement Caused by Intracellular Bacteria

BackgroundInfection of the central nervous system is a severe and fatal disease. Causative agents include bacteria, viruses or fungi. Intracellular bacteria are not only overlooked, but also underdiagnosed. We aimed to study the clinical, laboratory and evolutionary features of neurological involvement caused by intracellular bacteria.MethodsWe conducted a retrospective study including all patients hospitalized in the infectious disease department for neurological involvement caused by intracellular bacteria between 1995 and 2020. The diagnosis was confirmed by serology.ResultsWe encountered 76 cases among which 43 were males (56.6%). The mean age was 32±18 years. The revealing symptoms included fever (97.4%), cephalalgia (73.7%), vomiting (64.5%) and arthralgia (51.3%). Lumbar puncture revealed a median white blood cell count of 120[56-340]/mm3. Lymphocytic pleocytosis was noted in 62% of the cases. Elevated cerebrospinal fluid (CSF) protein level was noted in 37 cases (48.7%) with a median of 0.84[0.6-1.37] g/L. Low CSF fluid glucose level was noted in 14 cases (18.4%). There were 70 cases (92.1%) of meningitis and 6 cases of meningoencephalitis (7.9%). The causative agent included Rickettsia species in 47 cases (61.8%), Brucella species in 17 cases (22.4%) and Mycoplasma species in 12 cases (15.8%). Laboratory investigations included elevated C-reactive protein levels (40.7%), thrombocytopenia (32.8%) and increase in hepatic enzyme levels (21%). Anemia was noted in 27 cases (35.5%), leukocytosis in 24 cases (31.5%) and leucopoenia in 6 cases (7.8%). Blood and CSF cultures were positive for Brucella in 2 cases (2.6%) and 5 cases (6.5%), respectively. The mean duration of treatment was 156±94 days for brucellosis cases, 9±4 days for rickettsiosis cases and 10±6 days for Mycoplasma cases. The disease evolution was favorable in 72 cases (94.7%). Four patients were dead (5.3%). Complications were noted in 5 cases (6.5%) and sequelae in 2 cases (2.6%).ConclusionIntracellular bacteria including Brucella, Rickettsia and Mycoplasma species should be considered in front of neurological symptoms. Meningitis with lymphocytic pleocytosis was the most common clinical presentation. An early diagnosis followed by the adequate treatment might avoid complications and death.Disclosures All Authors: No reported disclosures

Methodological Features of the Spectrophotometric Determination of Proteins in Biological Fluids Using Reactions with Brompyrogallol Red

Methodological Features of the Spectrophotometric Determination of Proteins in Biological Fluids Using Reactions with Brompyrogallol Red

Evaluation of association between parameters related to penetration into cerebrospinal fluid and the microbiological efficacy of vancomycin in patients with bacterial meningitis

Vancomycin (VM) is used as empirical therapy for bacterial meningitis (BM). We investigated the relationship of the microbiological efficacy of VM for BM with VM minimum inhibitory concentration (MICVM), serum VM trough concentration (VMser) and cerebrospinal fluid (CSF) protein (P)/serum albumin (SA) ratio, which may reflect the extent of blood–brain barrier (BBB) disruption. Twelve BM patients were enrolled and VM was microbiologically effective in seven (58.3%). VMser, MICVM, and CSF-P/SA ratio were not associated with the microbiological efficacy of VM. The microbiological efficacy of VM was significantly associated with CSF-P/SA ratio multiplied by VMser relative to the MICVM (η = 0.61, p = 0.04). These results indicate that the parameter combining VMser, MICVM, and the extent of BBB disruption could be associated with the microbiological efficacy of VM in BM patients.

Correlation of Pregnancy-Associated Plasma Protein (PAPP-A) in Serum and Follicular Fluid with Oocyte and Embryo Quality in PCOS and non-PCOS Women Undergoing ICSI Cycle

Pregnancy-Associated Plasma Protein (PAPP-A) is a zinc metalloproteinase in the insulin growth factor system (IGFs) produced by the syncytiotrophoplast region of the placenta. It plays a critical function in the cleavage of IGFBP4. In the ovary IGFs, it regulates follicular and oocyte maturation, and steroidogenesis. While in polycystic ovarian syndrome (PCOS) Hyperinsulinemia and hyperandrogenemia it causes follicular environment changes and early ovulation resulting in lower oocyte and embryo quality in patients and this will decrease the success of pregnancy in women enrolled in the ICSI cycle. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid in women with PCOS and non-PCOS with oocyte and embryo quality in women undergoing ICSI cycle. 45 infertile Iraqi women were enrolled. Women with PCOS had to meet at least two of the three criteria set by the Rotterdam ESHRE/ASRMS criteria, the age of the included women ranged between 20-45 years. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without a statistically significant difference matching with PCOS group. In addition, there was no significant correlation between PAPP-A levels in serum and follicular fluid with oocytes and embryo characteristics. However, PAPP-A levels are higher in serum and follicular fluid in women with positive pregnancy but without significant differences. PAPP-A had no correlation with oocyte and embryo quality.

Biomarkers in rare neuromuscular diseases

Duchenne muscular dystrophy (DMD) is a severe, X-linked disease, affecting 1:5000 males, and characterized by progressive muscle weakness and muscle mass loss in children. Genetic and biochemical research over the years has led to the characterization of the genetic cause and pathophysiology of the disease. Moreover, the elucidation of genetic mechanisms underlining Duchenne muscular dystrophy has allowed the design of innovative personalized molecular therapies. The identification of specific, accurate, and sensitive biomarkers is becoming crucial for evaluating muscle disease progression and response to therapies, for disease monitoring, and to accelerate drug development and related regulatory processes. Several exploratory biomarkers have been discovered by analyzing DMD patients' cohorts and provided clues about tissue or fluid proteins and RNA biomarkers (Table 1), as well as allowed the identification of SNPs acting as DMD genetic modifiers (Table 2). Nevertheless, challenges were encountered in translating biomarkers into the clinical context and many bottlenecks still exist, hampering their adoption as surrogate endpoints. These issues could be overcome by national and international collaborative efforts, multicenter data sharing, and by the creation of large cohorts of patients as well as by the application of novel statistical tools, that can be effective also when patient numbers are small. Being DMD a Mendelian disease, building up “biomarker heatmaps” might help making multiple biomarkers applicable to clinical practice and possibly to clinical trials.

The molecular mechanism of the transcriptional activator SWI regulating gene ARID1B affecting swallowing dysfunction after stroke in rats.

Background: After a stroke, more than 50% of patients are suffering from dysphagia. Because the swallowing dysfunction is closely related to some neural pathways, the probing of the neuro-molecular mechanism of dysphagia is very important for future diagnosis and treatment. Methods: Our study is a typical causal study with the purpose of exploring molecular mechanisms. In this study, a rat model of dysphagia after stroke was constructed, and ARID1B overexpression plasmid was injected into the rat body through tail vein injection. The number of swallows and the swallowing response time induced by distilled water in each group of rats on the 7 th and 14 th day after modeling were detected. After 14 days of successful model establishment, the rat brain tissues were collected, part of the brainstem nucleus tractus solitarius and nucleus suspicious tissues were analyzed with a Ca2+ fluorescent indicator to analyze the intracellular concentration of Ca2+. For a part of the brainstem nucleus tractus solitarius and suspected nucleus tissues, immunohistochemistry was used to analyze the expression characteristics of genes ARID1B and TACR1 related proteins. The cerebrospinal fluid of brain tissue was collected, and the expression of gene TAC1 related protein in cerebrospinal fluid was analyzed by ELISA. For a part of the brainstem nucleus tractus solitarius and suspicious nucleus tissues, western blot was used to analyze the expression of gene SMARCA1 related protein, protein UNC80 and NALCN. Results: The detection of swallowing characteristics and the detection of intracellular Ca2+ concentration indicate the serious impact of stroke on swallowing function. The protein expression showed a consistent trend, which also showed that the overexpression of gene ARID1B can improve swallowing function to a certain extent. Conclusion: Due to our experiments, the molecular mechanism related to dysphagia was explored to a certain extent. At the same time, we found that the overexpression of the gene ARID1B can improve the swallowing function.

Антиоксидантная система респираторного тракта Антиоксидантные эффекторы в надэпителиальном и экстрацеллюлярном пространстве (часть 1)

В обзоре литературы изложены современные данные об антиоксидантной системе респираторного тракта. Показаны локализация компонентов и функционирование ферментного звена антиоксидантной системы в респираторном тракте. Дана характеристика протеинового состава жидкости бронхоальвеолярного лаважа. Представлено изменение содержания различных протеинов в жидкости бронхоальвеолярного лаважа после воздействия аллергеном у больных бронхиальной астмой. Показаны функции и локализация неферментных биоантиоксидантов бронхоальвеолярного секрета. Подробно рассмотрены характеристика, индукция синтеза и физиологическая роль в респираторном тракте антиоксидантного фермента бронхоальвеолярного секрета — экстрацеллюлярной супероксиддисмутазы.

Oligoclonal IgGs against DNA, Histones, and Myelin Basic Protein in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.

A study to observe quantitative levels of C- Reactive Protein in Cerebrospinal fluid in patients with Meningitis as an add-on routine investigation- a case-control study

Introduction: C-reactive protein (CRP) is a member of the class of acute phase reactants as itslevel rises dramatically during inflammatory processes occurring in the body. Measuring and chartingCRP values can prove useful in determining the disease progress. Aim: To estimate the CRP level inCerebrospinal fluid (CSF) of patients with meningitis; and to evaluate whether CRP levels could beused to differentiate the various types of meningitis in adults. Materials and Methods: This studywas a case-control study. 80 enrolled patients were subjected to a protocol that included detailedclinical history including duration of illness, symptoms and signs, history or any treatment history.Written informed consent was taken from the patients/guardian. Results: Meningitis was morecommon in the 18-30 years age group. Mean values of CSF CRP were- viral meningitis (2.70 mg/L)and pyogenic meningitis (91.13 mg/L) and control group (1.54 mg/L). CSF CRP can be used as adiagnostic tool to differentiate between pyogenic and viral meningitis as it is significantly raised inpyogenic meningitis in comparison to viral meningitis (p-value <0.0001). Conclusion: CRP in CSF isa valuable, rapid, bedside diagnostic test for differentiating between pyogenic and viral meningitis;with reasonably good sensitivity, specificity and positive predictive value. The absence of CRP in CSFrather than its presence is more important for the diagnosis of viral meningitis.

Clinical Characteristics of H1N1 Influenza A-Associated Mild Encephalopathy with Reversible Splenial Lesion: 4 Pediatric Cases.

Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

Sex-Related Differences in Cerebrospinal Fluid Plasma-Derived Proteins of Neurological Patients.

Background and aims: Cerebrospinal fluid (CSF) protein content presents a sexual dimorphism in humans. We investigated sex-related differences in CSF IgG levels and in the quantification of intrathecal IgG synthesis (IIS). Methods: CSF, serum albumin and IgG were measured in 1519 neurological patients and both linear and hyperbolic formulas were used for the quantification of IIS. CSF-restricted oligoclonal IgG bands (OCBs) were used as “gold standard”. Results: The linear IgG Index showed a weak agreement with OCBs in males and females (k = 0.559, k = 0.587, respectively), while the hyperbolic Reiber’s formulas had a moderate agreement with OCBs in females (k = 0.635) and a weak agreement in males (k = 0.565). Higher CSF albumin and IgG levels were found in men than in women in the whole population and in subjects without IIS after adjusting for age and for serum concentrations of albumin and IgG, respectively (Quade statistics, p < 0.000001). CSF and serum albumin and IgG levels positively correlated to age in both sexes. CSF total protein content did not correlate with CSF leukocyte numbers but was higher in patients with marked pleocytosis. Conclusions: In neurological patients, men have higher levels of CSF serum-derived proteins, such as albumin and IgG.

Risk factors for poor outcome in childhood tuberculous meningitis

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment.

Comparison of plasma and cerebrospinal fluid proteomes identifies gene products guiding adult neurogenesis and neural differentiation in birds

Cerebrospinal fluid (CSF) proteins regulate neurogenesis, brain homeostasis and participate in signalling during neuroinflammation. Even though birds represent valuable models for constitutive adult neurogenesis, current proteomic studies of the avian CSF are limited to chicken embryos. Here we use liquid chromatography–tandem mass spectrometry (nLC-MS/MS) to explore the proteomic composition of CSF and plasma in adult chickens (Gallus gallus) and evolutionarily derived parrots: budgerigar (Melopsittacus undulatus) and cockatiel (Nymphicus hollandicus). Because cockatiel lacks a complete genome information, we compared the cross-species protein identifications using the reference proteomes of three model avian species: chicken, budgerigar and zebra finch (Taeniopygia guttata) and found the highest identification rates when mapping against the phylogenetically closest species, the budgerigar. In total, we identified 483, 641 and 458 unique proteins consistently represented in the CSF and plasma of all chicken, budgerigar and cockatiel conspecifics, respectively. Comparative pathways analyses of CSF and blood plasma then indicated clusters of proteins involved in neurogenesis, neural development and neural differentiation overrepresented in CSF in each species. This study provides the first insight into the proteomics of adult avian CSF and plasma and brings novel evidence supporting the adult neurogenesis in birds.

Cerebrospinal Fluid and Serum C-Reactive Protein among Children with Acute Encephalitis Syndrome

Abstract Objectives This study aimed to evaluate the positivity of C-reactive protein (CRP) in cerebrospinal fluid (CSF) and serum in children presented with clinical diagnosis of acute encephalitis syndrome (AES). Methods A total of 164 children between 6 months and 14 years with clinical diagnosis of AES were investigated. Qualitative CRP (slide agglutination) was determined in CSF and serum sample of each patient. On the basis of clinical examination and investigations, all the patients were divided into four groups as pyogenic meningitis, viral encephalitis, tuberculous meningitis, and cerebral malaria. The positivity of CRP in CSF and serum were compared in these groups. Results CSF CRP was found to be positive in the majority of patients with pyogenic meningitis and a statistically significant (p ≤ 0.001) association was found between CSF CRP and final diagnosis of AES, while this association was nonsignificant (p = 0.141) in case of serum CRP. When we compared the CSF and serum CRP, serum CRP was found to be more suggestive of tuberculous meningitis, viral encephalitis, and cerebral malaria while CSF CRP was more sensitive and specific for the diagnosis of pyogenic meningitis. Conclusion The sensitivity and specificity of CSF CRP for pyogenic meningitis was quite high. Serum CRP with a high sensitivity can be used as a screening test for different types of meningitis and cerebral malaria; however, its diagnostic accuracy has yet to be established.

Quantitative proteomic profiling of Cervicovaginal fluid from pregnant women with term and preterm birth

BackgroundPreterm birth (PTB) is one of major causes of perinatal mortality and neonatal morbidity, but knowledge of its complex etiology is still limited. Here we present cervicovaginal fluid (CVF) protein profiles of pregnant women who subsequently delivered at spontaneous preterm or term, aiming to identify differentially expressed CVF proteins in PTB and term birth.MethodsThe CVF proteome of women who sequentially delivered at preterm and term was analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS). We compared the CVF proteome of PTB (n = 5) and control subjects (term birth, n = 7) using pooled control CVF (term birth, n = 20) as spike-in standard.ResultsWe identified 1294 CVF proteins, of which 605 were newly identified proteins. Of 990 proteins quantified in both PTB and term birth, 52 proteins were significantly up/down-regulated in PTB compared to term birth. The differentially expressed proteins were functionally associated to immune response, endopeptidase inhibitors and structural constituent of cytoskeleton. Finally, we confirm the down-regulation of SERPINB7 (a serine-type protease inhibitor) in PTB compared to control by Western blot.ConclusionsTaken together, our study provide quantitative CVF proteome profiles of pregnant women who ultimately delivered at preterm and term. These promising results could help to improve the understanding of PTB etiology and to discover biomarkers for asymptomatic PTB.

Novel Variants in the CLCN1, RYR2, and DCTN1 Found in Elderly Japanese Dementia Patients: A Case Series.

Dementia has an enormous impact on medical and financial resources in aging societies like Japan. Diagnosis of dementia can be made by physical and mental examinations, imaging tests, and findings of high abnormal proteins in cerebrospinal fluids. In addition, genetic tests can be performed in neurodegenerative diseases such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease (PD). In this case series, we presented three cases of dementia with unknown causes who carry novel variants in the genes associated with neurodegenerative diseases. Three patients (Patients 1, 2, and 6) were found by screening 18 dementia patients using a gene panel including 63 genes. The age of onset for Patient 1 was 74 years old, and his father had PD and mother had AD. The age of onset for Patient 2 was 75 years old, and her mother had AD. The age of onset for Patient 6 was 83 years old, and her father, two sisters, and daughter had dementia. The Mini-Mental State Examination produced results of 20, 15, and 22, respectively. The suspected diagnosis by neurological examinations and imaging studies for Patients 1 and 2 was AD, and for Patient 6 was FTD. Patient 1 was treated with donepezil; Patient 2 was treated with donepezil and memantine; and Patient 6 was treated with donepezil, galantamine, and rivastigmine. The three rare variants identified were: CLCN1, encoding a chloride channel, c.2848G>A:p.Glu950Lys (Patient 1); RYR2, encoding a calcium releasing ryanodine receptor, c.13175A>G:p.Lys4392Arg (Patient 2); and DCTN1, encoding a subunit of dynactin, c. 3209G>A:p.Arg1070Gln (Patient 6). The detected variants were interpreted according to the American College of Medical Genetics (ACMG) guidelines. The minor allele frequency for each variant was 0.025%, 0.023%, and 0.0004% in East Asians, respectively. The DCTN1 variant found in Patient 6 might be associated with FTD. Although none of them were previously reported in dementia patients, all variants were classified as variants of unknown significance (VUS). Our report suggests that results of genetic tests in elderly patients with dementia need to be carefully interpreted. Further data accumulation of genotype–phenotype relationships and development of appropriate functional models are warranted.

In silico data mining of human body fluids to unravel the immunomes in breast cancer

Breast cancer is asymptomatic with a poor prognosis at late stage. We used in-silico based proteomics data mining to identify immunoproteins in body fluids as potential indicators of onset and progression of breast cancer. We curated a list of differentially expressed proteins in tissue and body fluids (e.g. saliva and blood) on subtype and non-subtype specific breast cancer over the last 20 years, to show the extent of similarities in protein expression in tissue and bio-fluids. Based on specific selection criteria, significantly altered proteins were filtered to functionally annotate and analyze using different databases. Furthermore, the immunoproteins that showed cross-talks were further analyzed for amino-acid sequence-specific alterations associated with breast cancer to predict their potential impact on the disease. The curated datasets consolidated 4716 non-redundant proteins collectively in tissue, blood, and saliva from literature focused on subtype or non-subtype specific breast cancer. Of these immunoproteins, 39 (e.g., saliva) and 20 (e.g., blood) were found to cross-talk, of which 28 and 6 from saliva and blood, respectively, showed amino acid variations and were associated with breast cancer. Similarly, a total of 92 and 10 driver mutants were identified in saliva and blood, respectively, with ‘deleterious’ or ‘damaging’ impact on the biological function of a protein. The results of the study established correlations between expression profile and variation of immunoproteins with breast cancer to assess the cumulative effect of mutational hotspots and identify proteome-scale alterations that could trigger abnormal cell behavior.

Evaluation of the potential of Pap test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics

BackgroundThe purpose of this study was to determine whether the residual fixative from a liquid-based Pap test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap test or a cervical swab for the detection of ovarian cancer protein biomarkers.MethodsProteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap test fixative or eluted from the cervical swab. Protein was also extracted from the patient’s tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration.ResultsWe identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap test fluid and cervical swab proteins are similar to each other, and also to the tumor extract.ConclusionsOur results suggest that Pap test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a test for ovarian cancer detection.

Модификация метаболических нарушений в патогенезе спонтанных преждевременных родов

Objective. To determine the levels of interleukins, neopterin, S100β protein in amniotic fluid and cord blood, show their role in the pathogenesis of preterm birth and perinatal injury of the central nervous system (CNS) in newborns. Patients and methods. The study included 77 women randomly selected by simple randomization. A single-center, singlestage, controlled, randomized trial was conducted, which included 77 women comprising two groups: the main group – 33 patients with spontaneous preterm birth (35–37 weeks) and the control group – 44 women with the physiological course of pregnancy and childbirth (38–40 weeks). All newborns were also examined. The levels of interleukins IL-33 and IL-4, as well as neopterin and S100β protein were determined in amniotic fluid and cord blood by a solid-phase enzyme-linked immunosorbent assay (ELISA). Results. It was found that the increased production of interleukins and neurospecific proteins under study have a negative effect on the body of the pregnant woman and the fetus, which leads to serious pregnancy complications such as premature birth and perinatal CNS injury. Conclusion. The identified patterns provide a basis for the development of schemes for predicting preterm birth, which will improve perinatal outcomes and the health status of newborns. Key words: S100β protein, interleukins, neopterin, amniotic fluid, spontaneous preterm birth

Cytokine Profiling as A Potential Biomarker in Diffuse Large B-Cell Lymphoma

Cytokines are small proteins that mediate and regulate immunity. They are involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these cytokines may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many of these soluble proteins simultaneously, thus allowing rapid, cost-effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines from the serum derived from diffuse large b-cell lymphoma (DLBCL, n =11) and healthy volunteers (N, n =11) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these cytokines are significantly different in these two groups and explore the possible application of the cytokine as biomarkers in early-stage screening and/or surveillance. Our results show a significantly high level of IL-17A, IL-10 and IL-6 in DLBCL-derived serum compared to n-derived serum. These preliminary results were obtained from a small sample size and could be further validated with a larger sample size cohort to produce a panel of biomarkers for DLBCL. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.