Surface-enhanced Raman scattering (SERS) is a powerful technique for decoding of 2-5-component mixes of analytes. Low concentrations of analytes and complex biological media are usually non-decodable ...with SERS. Recognition molecules, such as antibodies and aptamers, provide an opportunity for a specific binding of ultra-low contents of analyte dissolved in complex biological media. Different approaches have been proposed to provide changes in SERS intensity of an external label upon binding of ultra-low contents of the analytes. In this paper, we propose a SERS-based sensor for the rapid and sensitive detection of botulinum toxin type A. The silver nanoisland SERS substrate was functionalized using an aptamer conjugated with a Raman label. The binding of the target affects the orientation of the label, providing changes in an analytical signal. This trick allowed detecting botulinum toxin type A in a one-stage manner without additional staining with a monotonous dose dependence and a limit of detection of 2.4 ng/mL. The proposed sensor architecture is consistent with the multiarray detection systems for multiplex analyses.
Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the ...study.
This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years.
SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (
= 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (
= 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (
= 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (
= 0.209). It was the same for patients without SIBO (
= 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (
= 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (
= 0.027) were significant independent risk factors for death in cirrhosis.
SIBO is associated with poor prognosis in cirrhosis.
Objective: According to the European guidelines for the prevention of cardiovascular diseases (CVD) (2021), Russia was identified as a country with a very high CV risk. We aimed to investigate the ...applicability of the standardized definitions of vascular aging phenotypes (VP) in Russian population and align them with the existing reference datasets. Design and method: In 2012-2013 1,600 residents of St. Petersburg (age 21-67) were randomly examined as a part of the multicenter epidemiological study. Anthropometry, blood pressure measurement, blood biochemistry analysis were taken. Subjects completed questionnaires describing their lifestyle, current health condition and medication usage. 618 patients (42% men) from initial cohort with a mean age of 48 37;55 years were randomly subsampled for carotid-femoral pulse wave velocity assessment (Sphygmocor). The VP were defined using the ‘Reference Values for Arterial Stiffness’ Collaboration database which included 16,867 measurements from eight European countries populations15 to 97 years. According to the criteria, patients with overt CVD, diabetes mellitus and the use of antihypertensive, lipid-lowering therapy were excluded from the analysis of VP. Results: The Russian cohort had significantly higher prevalence of CVD (11,4% compared to 6,9% in the Nreference population, p=5.65x10-5), intake of antihypertensives (28,1% compared to 14,3% in the reference, p<1x10-16) and lipid-lowering therapy (6,1% compared to 4,1%, p=0.025, Figure 1A). Additionally, our cohort had significantly higher prevalence of optimal BP (40,2% vs 28%, p=4.6x10-7) and lower prevalence of first-degree (p=0.048) and second degree (p=0.00084) hypertension (Figure 1B). Comparison of the prevalence of VP between the European and Russian cohorts showed a significant decrease of the early vascular aging (EVA) phenotype with age in the Russian population (p=0.011). The prevalence of the supernormal vascular aging phenotype (SUPERNOVA) in the group of 60-69 years old was higher in the Russian population (p=0.0035) Conclusions: A higher prevalence of CVD was demonstrated in the study cohort despite lower hypertension burden and higher CV drugs intake compared to the European cohort. Multidirectional trajectories of EVA and SUPERNOVA VP with age were detected in Russian population, potentially indicating the presence of the clearing selection pressure at the older age (Agreement No 075-15-2022-301).
The minimal inhibitory concentration (MIC) is conventionally used to define in vitro levels of susceptibility or resistance of a specific bacterial strain to an antibiotic and to predict its clinical ...efficacy. Along with MIC, other measures of bacteria resistance exist: the MIC determined at high bacterial inocula (MIC
) that allow the estimation of the occurrence of inoculum effect (IE) and the mutant prevention concentration, MPC. Together, MIC, MIC
and MPC represent the bacterial "resistance profile". In this paper, we provide a comprehensive analysis of such profiles of
strains that differ by meropenem susceptibility, ability to produce carbapenemases and specific carbapenemase types. In addition, we have analyzed inter-relations between the MIC, MIC
and MPC for each tested
strain. Low IE probability was detected with carbapenemase-non-producing
and high IE probability was detected with those that were carbapenemase-producing. MICs did not correlate with the MPCs; significant correlation was observed between the MIC
s and the MPCs, indicating that these bacteria/antibiotic characteristics display similar resistance properties of a given bacterial strain. To determine the possible resistance-related risk due to a given
strain, we propose determining the MIC
. This can more or less predict the MPC value of the particular strain.
Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been ...fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.
Valosin-containing human protein (VCP) or p97 performs enzyme functions associated with the maintenance of protein homeostasis and control of protein quality. Disruption of its normal functioning ...might be associated with the development of Parkinson's disease (PD). Tissues of mice with toxin-induced presymptomatic and early symptomatic stages of PD, as well as 52 treated and untreated patients with newly diagnosed PD and nine patients with a "predicted" form of PD, were investigated. Significant changes in Vcp gene expression were observed in almost all studied mouse tissues. A significant decrease in VCP expression specific for PD was also detected at both the late preclinical and the early clinical stages of PD in untreated patients. Thus, a decrease in VCP expression is important for changes in the function of the nervous system at early stages of PD. Analysis of changes in VCP expression in all patients with PD and in Vcp in the peripheral blood of mice used as models of PD revealed significant decreases in expression specific for PD. These data suggest that a decrease in the relative levels of VCP mRNA might serve as a biomarker for the development of pathology at the early clinical and preclinical stages of human PD.
Processes of intracellular and extracellular transport play one of the most important roles in the functioning of cells. Changes to transport mechanisms in a neuron can lead to the disruption of many ...cellular processes and even to cell death. It was shown that disruption of the processes of vesicular, axonal, and synaptic transport can lead to a number of diseases of the central nervous system, including Parkinson's disease (PD). Here, we studied changes in the expression of genes whose protein products are involved in the transport processes (
,
,
,
, and
) in the brain tissues and peripheral blood of mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced models of PD. We detected changes in the expressions of
,
, and
at the earliest modeling stages. Additionally, we have identified conspicuous changes in the expression level of
in the striatum and substantia nigra of mice with MPTP-induced models of PD in its early stages. These data clearly suggest the involvement of protein products in these genes in the earliest stages of the pathogenesis of PD.
Nucleic acid aptamers are prospective molecular recognizing elements. Similar to antibodies, aptamers are capable of providing specific recognition due to their spatial structure. However, the ...apparent simplicity of oligonucleotide folding is often elusive, as there is a balance between several conformations and, in some cases, oligomeric structures. This research is focused on establishing a thermodynamic background and the conformational heterogeneity of aptamers taking a series of thrombin DNA aptamers having G-quadruplex and duplex modules as an example. A series of aptamers with similar modular structures was characterized with spectroscopic and chromatographic techniques, providing examples of the conformational homogeneity of aptamers with high inhibitory activity, as well as a mixture of monomeric and oligomeric species for aptamers with low inhibitory activity. Thermodynamic parameters for aptamer unfolding were calculated, and their correlation with aptamer functional activity was found. Detailed analysis of thrombin complexes with G-quadruplex aptamers bound to exosite I revealed the similarity of the interfaces of aptamers with drastically different affinities to thrombin. It could be suggested that there are some events during complex formation that have a larger impact on the affinity than the states of initial and final macromolecules. Possible mechanisms of the complex formation and a role of the duplex module in the association process are discussed.
BACKGROUNDGut dysbiosis is common in cirrhosis. AIMTo study the influence of gut dysbiosis on prognosis in cirrhosis. METHODSThe case-control study included 48 in-patients with cirrhosis and 21 ...healthy controls. Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing. We used modified dysbiosis ratio (MDR): Bacilli (%) + Proteobacteria (%)/Clostridia (%) + Bacteroidetes (%). Patients with MDR more the median made up the group with severe dysbiosis, others did the group with non-severe dysbiosis. The follow-up period was 4 years. RESULTSThe mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis (54.2% vs 12.5%; P = 0.001). The presence of severe dysbiosis was independent risk factors for death hazard ratio = 8.6 × (1.9-38.0); P = 0.005. The abundance of Enterobacteriaceae (P = 0.002), Proteobacteria (P = 0.002), and Lactobacillaceae (P = 0.025) was increased and the abundance of Firmicutes (P = 0.025) and Clostridia (P = 0.045) was decreased in the deceased patients compared with the survivors. The deceased patients had a higher MDR value than the survivors 0.131 × (0.069-0.234) vs 0.034 × (0.009-0.096); P = 0.004. If we applied an MDR value of 0.14 as the cutoff point, then it predicted patient death within the next year with a sensitivity of 71.4% and a specificity of 82.9% area under the curve = 0.767 × (0.559-0.974). MDR was higher in patients with cirrhosis than in health controls 0.064 × (0.017-0.131) vs 0.005 × (0.002-0.007); P < 0.001, and in patients with decompensated cirrhosis than in patients with compensated cirrhosis 0.106 × (0.023-0.211) vs 0.033 × (0.012-0.074); P = 0.031. MDR correlated negatively with prothrombin (r = -0.295; P = 0.042), cholinesterase (r = -0.466; P = 0.014) and serum albumin (r = -0.449; P = 0.001) level and positively with Child-Turcotte-Pugh scale value (r = 0.360; P = 0.012). CONCLUSIONGut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.
PDF
