Serum Peptide Research Articles

A metagenome-wide association study of the gut microbiota in recurrent aphthous ulcer and regulation by thalidomide.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Serum peptidomic screening identified circulating peptide biomarkers predictive for preeclampsia.

BackgroundReliable biomarkers are needed to improve preeclampsia (PE) prediction accuracy. With the investigational tool of peptidomics, we aimed to identify and validate potential serum peptide biomarkers in cohorts suspected for PE development in middle or late pregnancy.MethodsTotally 195 serum samples were prospectively collected from pregnant women with PE-related syndromes who were followed up for PE development until delivery. Serum peptidomic analysis was performed in the discovery cohort of 115 samples using matrix-assisted laser desorption ionization-time of flight coupled with Linear Trap Quadropole Orbitrap mass spectrometry. The candidate biomarkers were further validated using an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method in an independent validation cohort of 80 serum samples.ResultsWe identified 8 peptides that were differentially expressed and originated from fibrinogen alpha chain (FGA), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and complement component 3. In the subsequent LC-MS/MS quantitation analysis, the levels of the three peptides (FGA-1033.4, ITIH4-2026.9, ITIH4-2051.1) exhibited a significant difference between the PE-positive and PE-negative groups. Further, the three-peptide panel yielded an area under the ROC curve (AUC) of 0.985 [95% confidence interval (CI) 0.965–1.000] and 0.923 (95% CI 0.845–1.000) in the discovery and validation cohorts respectively, with negative predictive values of 98.1–98.8% and positive predictive values of 73.1–85.3% that were much improved when compared with that of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio.ConclusionsWe have discovered and validated a novel three-peptide biomarker panel predictive for the occurrence PE in pregnant women.

Перинатальні наслідки при передчасному розриві плодових оболонок до 36 тижнів вагітності

The purpose - to evaluate the clinical status of newborns in women with pregnancy complicated by preterm premature rupture of membranes (pPROM) and its relationship with the course of pregnancy and childbirth, the duration of the latency period between pPROM and delivery (LP), as well as with the levels of vitamin 25(OH)D and the expression of antimicrobial peptides (β-defensins 2) in the mother’s blood. Materials and methods. The condition and morbidity of newborns with preterm birth due to pPROM have been carefully studied. The levels of vitamin 25(OH)D and the expression of antimicrobial peptides (β-defensins 2) in the blood serum of 109 women with singleton pregnancy complicated by pPROM at 23-36 weeks of gestation and 20 pregnant women of the control group with intact membranes, who subsequently gave birth to full-term babies, were studied by enzyme-linked immunosorbent assay. Results. No significant relationship between the condition of newborns and the duration of LP was found. Medical tactics of pregnancy management with pPROM led to the presence of a direct relationship between the prolongation of LP and the prevention of respiratory distress syndrome with dexamethasone/betamethasone (r=+0.36; p<0.001), tocolytic therapy with nifedipine (r=+0.30; p<0.01) against the background of antibacterial therapy. Groups of pregnant women with different duration of LP were statistically comparable in terms of gestation at the time of delivery. The average content of vitamin 25(OH)D in the blood of pregnant women with pPROM was reduced by half (26.3±0.9 pg/ml vs. 52.9±2.4 pg/ml), and the expression level of β-defensins 2 - by 1.4 times compared to the control group (78.4±1.8 pg/ml vs. 107.4±2.6 pg/ml). It has been confirmed that the level of vitamin 25(OH)D in the blood of women with pregnancy complicated by pPROM is directly associated with the gestational age of the newborn (r=+0.22; p<0.05) and the corresponding assessments of its condition. Reliable associations of the expression level of β-defensins 2 in the mother's blood with the indicators of the course of pregnancy and perinatal period, as well as with certain characteristics of the condition of newborns were found. Conclusions. No reliable association between the condition of newborns and the LP was found, which can be explained by the adequate tactics of managing pregnant women with pPROM. A significant decrease in the levels of vitamin 25(OH)D and the expression of antimicrobial peptides (β-defensins 2) in blood serum of the examined pregnant women with pPROM compared to the control group was determined. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients was obtained for conducting the studies. No conflict of interests was declared by the authors.

ST2 and copeptine – modern biomarkers for monitoring the effectiveness of treatment of decompensated heart failure in patients after acute myocardial infarction

The aim of the study was to increase the efficiency of diagnostic methods to find means to improve the treatment of patients with decompensated heart failure in the post-infarction period.
 Materials and methods. This study is based on an examination of 120 patients with decompensated HF (60 patients with STEMI and 60 with non-STEMI). Patients with previous STEMI complicated by decompensated heart failure were divided into groups, depending on their treatment. The studied groups were homogeneous in terms of age, sex, the severity of the course of the disease, duration of the post-infarction period, and the presence of clinical manifestations of decompensation. The patients were observed on the first day after hospitalization, after 1 and 2 months after treatment. Copeptin serum levels were assayed using the EK 065-32, EIA Copeptine kit (RayBiotech, Inc., USA). ST-2 in blood serum was determined with the help of the Presage ST-2 kit (Critical Diagnostics, USA). The level of ST2 was determined in ng/ml.
 Results. We analysed the effect of therapy on the level of ST2 in the blood serum of examined patients with STEMI and non-STEMI complicated by decompensated heart failure. All the treatment regimens we proposed led to a significant decrease in the level of this peptide in blood serum after the end of the treatment. In patients of group I who received basic therapy drugs, the average ST2 concentration was (49.47±1.77) ng/ml before treatment. After 1 and 2 months of therapy, it was (44.92±1.22) ng/ml and (41.67±1.18) ng/ml, respectively (p˂0.05). The patients with decompensated heart failure after non-STEMI from group I had a copeptin level of (18.13±0.10) pg/ml before treatment and probably decreased to levels of (16.29±0.15) pg/ml and (15.09±0.14) pg/ml after 1 and 2 months under the influence standard therapy.
 Conclusions. We found the dependence of copeptin and ST2 levels on decompensated HF in the early and late post-infarction periods. It was established that the use of the therapy with a combination of the studied drugs led to a more intense decrease in serum copeptin, compared to therapy with succinic acid, arginine drugs, and standard therapy (p˂0.05). Using a differentiated treatment algorithm for patients with decompensated heart failure in the post-infarction period, copeptin and ST2 in blood serum increases the effectiveness of treatment and prevents complications.

Diagnosis and subtype classification on serum peptide fingerprints by mesoporous polydopamine with built-in metal-organic framework

Crohn's disease (CD) as a big issue to public health needs an accurate diagnosis urgently that is the common challenge among internal diseases. Herein, we design a mesoporous polydopamine with built-in metal-organic frameworks (dubbed MMP-b-MOFs) to combine with high-throughput mass spectrometry to extract serum peptide fingerprints from CD and healthy controls (HC). Benefitting by the size-exclusion and strong hydrophilicity of MMP-b-MOFs, the extracted peptide fingerprints present extremely high quality. CD and HC are explicitly discriminated with orthogonal partial least squares discriminant analysis (OPLS-DA), the corresponding area under the curve (AUC) value is 1.000. Moreover, eight peptides with clear identity are screened out and achieve the accurate diagnosis and subtype classification of CD, with all AUC values up to 1.000. Moreover, the unsupervised model is also established to precisely classify HC and CD based on these eight clearly identified peptides. This work brings great benefits for clinical detection especially internal medicine.

Derivatization to increase the detectability of small peptides in blood serum in the analysis by ESI and MALDI high resolution mass spectrometric methods

This work highlights the efficient approach to highly sensitive determination of dipeptides that can present in biological liquids at very low and trace quantities. The approach involves preliminary derivatization of peptides with tris(2,4,6-trimethoxyphenyl)-methyl carbenium hexafluoroborate followed by ESI and MALDI high-resolution mass spectrometry. Using model dipeptides with various amino acid compositions and sequences, it was shown that the derivatization reaction proceeded smoothly in mild conditions and gave rise to pink-red colored salt derivatives. Ready cations of interest for the analysis are easily desorbed from the salt-derivatives providing strong signals in ESI and MALDI mass spectra and this ensures high sensitivity of the analysis. Another positive aspect is the removal of the target signal from the region of a matrix noise, since the introduced fragment possesses a large mass increment (359 Da). High resolution mass spectrometry, which provides the determination of accurate weights and elemental compositions of ions, was used to reliably detect model dipeptides added to artificial urine and blood serum. A number of these dipeptides was shown to be present in real blood serum collected from volunteers. Collision induced dissociation of precursor cations composed of derivatizing reagent and dipeptide moieties gives rise to characteristic and simple fragmentation mass spectra. A comparison of limits of detection (LOD) measured for non-modified and derivatized dipeptides showed that the latter derivatives provide the highest sensitivity when LOD is determined by using multiple reaction monitoring (MRM) transitions. The suggested derivatization approach was shown to be useful for unambiguous identification of special dipeptides in artificial media and dietary supplements.

Serum peptidome profiles immune response of COVID-19 Vaccine administration.

BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings.MethodsWe performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information.ResultsSignificant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR).ConclusionsThe study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

A Peptidomic Approach to Identify Novel Antigen Biomarkers for the Diagnosis of Tuberculosis.

BackgroundHere, we conducted a peptidomic study in murine model to identify novel antigen biomarkers for the diagnosis of tuberculosis (TB) with improved performance.MethodsFour recombinant proteins, including Mycobacterium tuberculosis protein 32 (MPT32), Mycobacterium tuberculosis protein 64 (MPT64), culture filtrate protein 10 (CFP10), and phosphate ABC transporter substrate-binding lipoprotein (PstS1) were expressed and intravenously injected into BALB/c mice. The serum were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of candidate peptides in serum of suspected TB patients were determined using competitive enzyme-linked immunosorbent assay.ResultsA total of 65 peptides from 4 MTB precursor recombinant proteins were identified in mouse serum by LC-MS/MS, of which 5 peptides were selected as candidates for serological analysis. The concentrations of peptides MPT64-2, CFP10-2 and PstS1-2 in TB patients were significantly higher than those in non-TB patients. MPT64-2 exhibited the most promising sensitivity (81.4%), followed by PstS1-2 and CFP10-2. In addition, PstS1-2 had the highest specificity (93.3%), followed by CFP10-2 and MPT64-2. According to the area under the curve (AUC), MPT64-2 (AUC = 0.863), PstS1-2 (AUC = 0.812) and CFP10-2 (AUC = 0.809) exhibited better diagnostic validity.ConclusionWe develop an effective approach to identify new antigen biomarkers via LC-MS/MS-based peptidomics. Multiple peptides exhibit promising efficacy in diagnosis of active TB patients.

TamaFlex™-A novel nutraceutical blend improves lameness and joint functions in working horses.

BackgroundLameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti‐inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio.MethodsWe conducted a 12‐week single‐center, randomized, blinded, placebo‐controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2–4 on the American Association of Equine Practitioners (AAEP) scale. Twenty‐two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or placebo over a period of 84 days. Improvement in lameness over placebo was the primary endpoint, and changes in the levels of rheumatoid factor (RF), anti‐nuclear antibody (ANA), and anti‐cyclic citrullinated peptide (ACC‐peptide) in serum, and pro‐inflammatory cytokines including interleukin (IL‐1β and IL‐6), tumor necrosis factor‐α (TNF‐α) and prostaglandin‐E2 (PGE2) in serum and synovial fluid were the secondary endpoints.ResultsNXT15906F6 exhibited significant relief from lameness in a time‐dependent manner. NXT15906F6 also reduced levels of ANA, PGE2, IL‐1β, TNF‐α and IL‐6. Moreover, NXT15906F6 supplementation is safe and tolerable in alleviating joint pain in lame horses, and protects the joints from further degradation by reducing pro‐inflammatory mediators.ConclusionNXT15906F6 significantly reduces the lameness during walking and trotting, leading to an improvement in their joint flexibility, health, and working performances.

Hemopexin as a Potential Binding Partner of Arginine-Rich Cell-Penetrating Peptides in Serum.

Serum proteins affect the in vivo fate and cellular uptake of arginine-rich cell-penetrating peptides (CPPs) and drugs delivered by CPPs. Although the binding of CPPs to serum proteins may possibly reduce their cellular uptake to some extent, it may also prolong their circulation half-life in vivo. We aimed to identify novel binding proteins of arginine-rich CPPs in serum to better understand their in vivo fate and develop more sophisticated drug delivery systems using CPPs. Isothermal titration calorimetry analysis suggests that albumin, the most abundant protein in serum, binds to d-forms of oligoarginine; however, the dissociation constants are several tens of a micromolar. Candidate proteins with the potential of binding to arginine-rich CPPs in serum were then explored using nondenaturing polyacrylamide gel electrophoresis followed by mass spectrometry analysis. Studies using fluorescence correlation spectroscopy determined hemopexin as a potential binding partner of d-forms of arginine-rich CPPs, including d-octaarginine (r 8) and the d-form of the peptide, corresponding to HIV-1 Rev (34-50), with dissociation constants of submicromolar to micromolar range. Using flow cytometry and a split-luciferase-based system, the promotion effect of hemopexin on the total cellular uptake and cytosolic localization of cargos conjugated with these CPPs was confirmed. Therefore, this study elucidated hemopexin as a potential binding partner of d-arginine-rich CPPs that may affect their in vivo fate and cellular uptake.

Differences in cognition, short-chain fatty acids and related metabolites in pregnant versus non-pregnant women: a cross-sectional study

BackgroundPregnancy induces cognitive reorganization which can lead to mental disorders. The aim of this study is to determine differences in cognitive scores, short-chain fatty acids (SCFAs) and related metabolites between pregnant and non-pregnant participants.MethodsThis cross-sectional study included 67 full-term pregnant women and 31 non-pregnant women. We compared scores of mental state and cognitive assessment tests, as well as serum concentrations of SCFAs, hormones, inflammatory factors, and neurotransmitters between these groups.ResultsScores for information processing speed, immediate visual memory, motor response speed and accuracy, execution ability and verbal use ability in the pregnant group were lower than those in the non-pregnant group (p < 0.05 for all tests). Total serum SCFAs in the pregnant group were significantly lower than those in the non-pregnant group (P = 0.031). Among them, acetate and propionate were significantly decreased (P = 0.013 and 0.037, respectively) whereas butyrate was significantly increased (P = 0.035). Serum peptide YY, glucagon-like peptide-1, γ-aminobutyric acid, and dopamine showed no differences between the two groups. However, cortisol, adrenocorticotropic hormone, and acetylcholine were significantly increased in the pregnant group as compared with the non-pregnant group (P = 0.039, 0.016, and 0.012, respectively). Tumor necrosis factor-α was increased and interleukin-10 significantly decreased in the pregnant group (P = 0.045 and 0.019, respectively).ConclusionAccording to our study findings, cognitive reorganization in the third trimester of pregnancy showed that both the passive storage capacity of working memory and the executive function of online information processing were decreased to varying degrees. At the same time, the changes in total SCFAs, the proportions of SCFAs and related metabolites were also detected. These changes in the internal environment may be increasing the risk of perinatal mental illness.

MO094: Intensive Blood Pressure Lowering and Myocardial Fibrosis Biomarkers in Individuals With and Without CKD: Results From the Systolic Blood Pressure Intervention Trial (Sprint)

Abstract BACKGROUND AND AIMS Circulating cardiac biomarkers implicated in the pathogenesis of heart disease may provide a non-invasive, more precise assessment of cardiovascular risk. In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive blood pressure lowering was associated with a 25% reduction in cardiovascular events and a 27% reduction in all-cause mortality. We sought to assess whether the beneficial effect of lowering systolic blood pressure on clinical outcomes was accompanied by a reduction in serum biomarkers of myocardial fibrosis. METHOD SPRINT, a multicenter randomized controlled trial conducted in the United States, enrolled participants aged ≥ 50 years, at increased risk for cardiovascular disease and randomized them to intensive systolic blood pressure lowering (target &amp;lt; 120 mmHg) or standard blood pressure lowering (target &amp;lt; 140 mmHg). In a randomly selected subgroup of SPRINT participants, myocardial fibrosis was assessed by two collagen-derived serum peptides, C-terminal propeptide of procollagen type I (CICP) and N-terminal propeptide of procollagen type 3 (P3NP) and Galectin 3 measured at study baseline and at 24 months follow-up. Chronic kidney disease was defined as eGFR &amp;lt; 60 mL/min/1.73 m2. Analyses were based on linear mixed models including clinic site as a random effect, with adjustments for treatment group and baseline level of each respective biomarker. RESULTS A total of 742 SPRINT participants with and without CKD with available measurements of myocardial fibrosis biomarkers at study baseline and 24 months were included in the study. The median (IQR) Galectin 3, CICP and P3NP levels at study baseline and 24 months follow-up in the intensive versus standard group are presented in the Table 1. Intensive blood pressure lowering was not associated with longitudinal changes in CICP or P3NP (Table 1 and Figure 1). Intensive blood pressure lowering was associated with a statistically significant increase in Galectin 3 level [between group mean difference 0.47 (IQR: 0.03–0.92) ng/mL, P = 0.04]. All of the findings were generally consistent across participants with and without CKD (Table 1). CONCLUSION In a random sample of SPRINT participants, intensive versus standard blood pressure lowering was not associated with a reduction in circulating myocardial fibrosis biomarkers overtime in hypertensive individuals with and without CKD.

Search and investigation of potential peptide agents of interaction between human organism and its microbiome

Symbiotic interaction between the human body and its microbiota is an important issue of modern biomedicine and personalized medicine. However, little is known on molecular mechanisms of that relationship. Bearing in mind the ubiquitous participation of peptides in biomolecular interactions and regulatory processes we attempted direct search of blood peptides originated from microbial proteins. LC‐MS/MS analysis was carried out of blood serum and plasma samples taken from 20 healthy donors on Q Exactive HF‐X Hybrid Quadrupole‐Orbitrap mass‐spectrometer. Sample preparation was carried out based on our previously developed method of peptide desorption from the surface of major blood plasma proteins followed by standard chromatographic steps. Human microbiota protein sequences were taken from NIH Human Microbiome Project.As a result, out of 13,625 identified peptides 912 were unique fragments of microbial precursors, which is about 6.69% of the total amount of detected bloodstream peptides. In 30 cases peptide identification was confirmed by mass‐spectral study of individual synthetic samples. Absolute quantification by the mass‐spectrometric method of multiple reaction monitoring (MRM) confirmed the presence of bacterial peptides in plasma and serum in the range of approximately 0.1 nM to 1 uM, which is comparable to physiologically significant hormone concentrations in human blood in normal conditions. The abundance of microbiota peptides reaches its maximum 5h after a meal. Most of the peptides correlate with the bacterial composition of the small intestine and are likely obtained by hydrolysis of membrane proteins with trypsin, chymotrypsin and pepsin — the main proteases of the gastrointestinal tract.The isolated fraction of peripheral blood mononuclear cells showed increase secretion of proinflammatory cytokines, colony stimulating factors and chemoattractants as the response to the addition of some of the identified microbiotic peptides. Such peptides — identified both in the plasma and in the serum — have properties of resistance to fibrinolysis, since the pool of peptides is preserved after passing through the digestive tract. The physicochemical properties of the identified bacterial peptides are consistent with those required for the selective permeability of mucosal barriers. Our approach to the identification of microbiota peptides in the blood serum and plasma may be useful for determining the microbiota composition of hard‐to‐reach intestinal areas, such as the small intestine, and for monitoring the permeability of the intestinal mucosal barrier.

Antibody and T Cell Immune Responses to SARS-CoV-2 Peptides in COVID-19 Convalescent Patients.

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

Diagnostic markers of early metabolic disorders in workers of an oil-producing enterprise

The oil industry is a significant component of the industry of Bashkortostan. The complex of harmful factors for oil production workers includes industrial noise, vibration, exposure to harmful substances, the severity and intensity of work, unfavorable microclimate conditions. The researchers conditionally divide production factors of chemical nature into natural chemicals that are part of oil and associated gases (hydrocarbons, hydrogen sulfide, carbon monoxide, nitrogen oxide, mercaptans), and substances used to enhance oil recovery, preparation, transportation of oil and gas (reagents, acids, surfactants, methanol, welding aerosols). There is a role of changes in metabolic processes at the level of cells and subcellular structures in the development of pathological processes under the influence of harmful production factors in a number of studies. The study aims to substantiate the markers of early metabolic disorders in employees of an oil-producing enterprise. We conducted a study of metabolic processes in 340 oil production workers. The researchers represented the professional production groups by drillers (35.3%), operators of underground well repair (64.7%). The authors carried out characteristics of the factors of the working environment and the labor process of oil-producing industries in accordance with R 2.2.2006-05. The researchers also performed biochemical studies of the parameters of the lipid spectrum of blood serum, free radical processes and endogenous intoxication. The level of exposure to the average concentrations of the chemical factor at the workplaces of drillers and operators of underground well repair corresponds to classes 2-3.1. The influence of harmful production factors causes metabolic disorders in the body of oil production workers in the form of a violation of the lipid spectrum (an increase in total cholesterol, triglycerides), changes in the activity of cytolytic enzymes (GGT, AST, ALT), activation of lipid peroxidation processes, a decrease in catalase activity, an increase in the level of medium-molecular peptides in blood serum, which confirms the presence of endogenous intoxication syndrome in the examined workers. The impact of harmful production factors on the body of oil production workers causes metabolic disorders in the body and dictates the need for a complex of biochemical studies for the early diagnosis of prenosological processes and timely preventive measures.

A Novel Trimethylamine Oxide-Induced Model Implicates Gut Microbiota-Related Mechanisms in Frailty.

Frailty is a complicated syndrome that occurs at various ages, with highest incidence in aged populations, suggesting associations between the pathogenesis of frailty and age-related changes. Gut microbiota (GM) diversity and abundance change with age, accompanied by increased levels of trimethylamine oxide (TMAO), a systemic inflammation-inducing GM metabolite. Thus, we hypothesized that TMAO may be involved in the development of frailty. We successfully established and verified a novel model of frailty in adult mice based on a 4-week intraperitoneal injection regime of TMAO followed by LPS challenge. The frailty index significantly increased in TMAO-treated mice after LPS challenge. TMAO also decreased claudin-1 immunofluorescent staining intensity in the jejunum, ileum, and colon, indicating that the destruction of intestinal wall integrity may increase vulnerability to exogenous pathogens and invoke frailty. 16S sequencing showed that TMAO significantly reduced the GM Firmicutes/Bacteroidetes (F/B) ratio, but not α-diversity. Interestingly, after LPS challenge, more genera of bacterial taxa were differently altered in the control mice than in the TMAO-treated mice. We infer that a variety of GM participate in the maintenance of homeostasis, whereas TMAO could blunt the GM and impair the ability to recover from pathogens, which may explain the continuous increase in the frailty index in TMAO-treated mice after LPS challenge. TMAO also significantly increased serum imidazole metabolites, and led to different patterns of change in serum peptide and phenylpropanoid metabolites after LPS stimulation. These changes indicate that glucose metabolism may be one mechanism by which GM inactivation causes frailty. In conclusion, TMAO leads to frailty by destroying intestinal barrier integrity and blunting the GM response.

Tau and Amyloid-β Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters.

Relevance of blood-based biomarkers is increasing into the neurodegenerative diseases field, but data on Parkinson's disease (PD) remain still scarce. In this study, we used the SiMoA technique to measure serum content of total tau protein and amyloid-β peptides (Aβ-42, Aβ-40) in 22 PD patients and ten control subjects. Serum levels of each biomarker were correlated with the respective CSF levels in both the groups; in PD patients, also the correlations between serum biomarkers and main clinical parameters were tested (motor, non-motor, cognitive scores and levodopa equivalent daily dose). Serum biomarkers did not exhibit quantitative differences between patients and controls; however, only PD patients had inter-fluids (serum-CSF) associations in tau and amyloid-β-42 levels. Moreover, serum content of tau protein was inversely correlated with cognitive performances (MoCA score). These findings, albeit preliminary, indicate that brain-derived peptides may change in parallel in both peripheral blood and CSF of PD patients, eventually even in association with some clinical features. Further studies are now needed to validate the use of blood-based biomarkers in PD.

MALDI-TOF-MS analysis in low molecular weight serum peptidome biomarkers for NSCLC.

ObjectsLung cancer is one of the leading causes of death from cancer in the world. Screening new serum biomarkers is important for the early detection of lung cancer. The purpose of this study was to investigate the serum peptide model between non‐small cell lung cancer (NSCLC) patients and healthy controls, as well as between paired pre‐ and postoperative NSCLC patients, and to find the low molecular weight (LMW) potential tumor markers for NSCLC.Methods56 serum samples from NSCLC patients, 56 controls, and 20 matched pre‐ and postoperative patients were analyzed using magnetic‐bead (MB)‐based purification technique combined with MALDI‐TOF‐MS. To distinguish NSCLC from cancer‐free controls, three models were established. Finally, comparing the three groups of serum protein fingerprints, nano‐liquid chromatography–electrospray ionization tandem mass spectrometry was used to further identify the differential peptides.ResultsAmong the three models constructed, the GA model had the best diagnostic efficacy. Five differential peaks were screened by combining the case group, healthy controls, and postoperative group analysis, which were up‐regulated in the case group and showed a tendency to return to healthy control values after surgery. The protein matching the mass spectrometry peak m/z 2953.73 was identified as fibrinogen α chain.ConclusionThis study shows that the application of MALDI‐TOF‐MS is a promising approach for the identification of potential serum biomarkers for NSCLC, which is potentially valuable for establishing a new diagnostic method for lung cancer. In addition, we found that fibrinogen α chain may be an auxiliary diagnostic indicator for NSCLC.

The lipid components of high-density lipoproteins (HDL) are essential for the binding and transportation of antimicrobial peptides in human serum

Antimicrobial peptides (AMPs) have been developed for the treatment of bacterial infections, but their applications are limited to topical infections since they are sequestered and inhibited in serum. Here we have discovered that the inhibition of AMPs by human serum was mediated through high-density lipoproteins (HDL) which are known to remove cholesterol from peripheral tissues. The susceptibility of AMPs to HDL varied depending on the degree of hydrophobicity of AMPs and their binding affinities to HDL. The phospholipids, such as phosphatidylcholine, of HDL were essential for AMP-binding. The dynamic binding interactions between AMPs and HDL were mediated through the hydrophobic interactions rather than by ionic strength. Interestingly, some AMPs, such as SMAP29, dissociated from the AMP-HDL complex and translocated to bacteria upon contact, while some AMPs, such as LL37, remained in complex with HDL. These results suggest that HDL binds AMPs and facilitates the translocation of them to the bacteria.

The Expression Significance of LPa, BNP, and McP-1 in CHD Patients and Their Relationship with Echocardiographic Parameters.

In order to investigate the expression levels of Lipoprotein A (LPa), B-type Natriuretic Peptide (BNP) and Monocyte chemoattractor Protein-1 (McP-1) in serum of patients with coronary heart disease (CHD) are used to detect significance and to analyze the correlation between these indicators and parameters of echocardiography. The clinical data of 132 CHD patients in our hospital from January 2021 to October 2021 are retrospectively analyzed and included in the CHD group. Another 100 healthy people who came to our hospital for general physical examination were selected as the control group. The expressions of Serum McP-1 and BNP are detected by the ELISA. The expression of Serum LPa is detected by immunoturbidimetry, and the expressions of SERUM McP-1, BNP, and LPa are compared between the two groups. The experiments show that the expressions of McP-1, BNP, and LPa in serum of control group are significantly lower than those of the CHD group (P < 0.05). Echocardiography results show that left ventricular ejection fraction (LVEF) in CHD group is significantly lower than that in control group, but left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) are significantly higher than those in control group (P < 0.05).