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1.
Psychoneuroendocrinology ; 166: 107062, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38678733

Adverse childhood experiences (ACEs) are a well-known risk factor of schizophrenia. Moreover, individuals with schizophrenia are likely to use maladaptive stress coping strategies. Although it has been reported that a history of ACEs might be associated with a pro-inflammatory phenotype in patients with schizophrenia, the interacting effect of coping styles on this association has not been tested so far. In the present study, we aimed to investigate the levels of immune-inflammatory markers in patients with schizophrenia and healthy controls (HCs), taking into consideration a history of ACEs and coping strategies. Participants included 119 patients with schizophrenia and 120 HCs. Serum levels of 26 immune-inflammatory markers were determined. A history of any categories of ACEs was significantly more frequent in patients with schizophrenia. Moreover, patients with schizophrenia were significantly more likely to use emotion-focused coping and less likely to use active coping strategies compared to HCs. The levels of interleukin(IL)-6, RANTES, and tumor necrosis factor-α (TNF-α), appeared to be elevated in patients with schizophrenia after adjustment for potential confounding factors in all tested models. Participants reporting a history of any ACEs had significantly higher levels of TNF-α and IL-6. No significant main and interactive effects of active strategies as the predominant coping on immune-inflammatory markers with altered levels in patients with schizophrenia were found. Findings from the present study indicate that ACEs are associated with elevated TNF-α and IL-6 levels regardless of schizophrenia diagnosis and predominant coping styles.

3.
J Autoimmun ; 145: 103204, 2024 May.
Article En | MEDLINE | ID: mdl-38520895

Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress ß1-tubulin and ß-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding ß1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.


Blood Platelets , Cytoskeletal Proteins , Cytoskeleton , Multiple Sclerosis , Tubulin , Humans , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Multiple Sclerosis/blood , Blood Platelets/metabolism , Tubulin/metabolism , Tubulin/genetics , Female , Cytoskeleton/metabolism , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Adult , Male , Middle Aged , Actins/metabolism , Actins/genetics , Megakaryocytes/metabolism , Megakaryocytes/pathology , Protein Processing, Post-Translational , Mutation
4.
Sci Rep ; 14(1): 3046, 2024 02 06.
Article En | MEDLINE | ID: mdl-38321199

Tanshinones, are a group of diterpenoid red pigments present in Danshen - an important herbal drug of Traditional Chinese Medicine which is a dried root of Salvia miltiorrhiza Bunge. Some of the tanshinones are sought after as pharmacologically active natural products. To date, the biosynthetic pathway of tanshinones has been only partially elucidated. These compounds are also present in some of the other Salvia species, i.a. from subgenus Perovskia, such as S. abrotanoides (Kar.) Sytsma and S. yangii B.T. Drew. Despite of the close genetic relationship between these species, significant qualitative differences in their diterpenoid profile have been discovered. In this work, we have used the Liquid Chromatography-Mass Spectrometry analysis to follow the content of diterpenoids during the vegetation season, which confirmed our previous observations of a diverse diterpenoid profile. As metabolic differences are reflected in different transcript profile of a species or tissues, we used metabolomics-guided transcriptomic approach to select candidate genes, which expression possibly led to observed chemical differences. Using an RNA-sequencing technology we have sequenced and de novo assembled transcriptomes of leaves and roots of S. abrotanoides and S. yangii. As a result, 134,443 transcripts were annotated by UniProt and 56,693 of them were assigned as Viridiplantae. In order to seek for differences, the differential expression analysis was performed, which revealed that 463, 362, 922 and 835 genes indicated changes in expression in four comparisons. GO enrichment analysis and KEGG functional analysis of selected DEGs were performed. The homology and expression of two gene families, associated with downstream steps of tanshinone and carnosic acid biosynthesis were studied, namely: cytochromes P-450 and 2-oxoglutarate-dependend dioxygenases. Additionally, BLAST analysis revealed existence of 39 different transcripts related to abietane diterpenoid biosynthesis in transcriptomes of S. abrotanoides and S. yangii. We have used quantitative real-time RT-PCR analysis of selected candidate genes, to follow their expression levels over the vegetative season. A hypothesis of an existence of a multifunctional CYP76AH89 in transcriptomes of S. abrotanoides and S. yangii is discussed and potential roles of other CYP450 homologs are speculated. By using the comparative transcriptomic approach, we have generated a dataset of candidate genes which provides a valuable resource for further elucidation of tanshinone biosynthesis. In a long run, our investigation may lead to optimization of diterpenoid profile in S. abrotanoides and S. yangii, which may become an alternative source of tanshinones for further research on their bioactivity and pharmacological therapy.


Salvia miltiorrhiza , Salvia , Salvia/metabolism , Abietanes , Salvia miltiorrhiza/genetics , Gene Expression Profiling , Cytochrome P-450 Enzyme System/genetics , Plant Roots/metabolism
5.
Int J Mol Sci ; 25(2)2024 Jan 13.
Article En | MEDLINE | ID: mdl-38256072

Brassinosteroids (BRs) are a class of plant steroid hormones that are essential for plant growth and development. BRs control important agronomic traits and responses to abiotic stresses. Through the signaling pathway, BRs control the expression of thousands of genes, resulting in a variety of biological responses. The key effectors of the BR pathway are two transcription factors (TFs): BRASSINAZOLE RESISTANT 1 (BZR1) and BRI1-EMSSUPPRESSOR 1 (BES1). Both TFs are phosphorylated and inactivated by the Glycogen synthase kinase 3 BRASSINOSTEROID INSENSITIVE2 (BIN2), which acts as a negative regulator of the BR pathway. In our study, we describe the functional characteristics of HvGSK1.1, which is one of the GSK3/SHAGGY-like orthologs in barley. We generated mutant lines of HvGSK1.1 using CRISPR/Cas9 genome editing technology. Next Generation Sequencing (NGS) of the edited region of the HvGSK1.1 showed a wide variety of mutations. Most of the changes (frameshift, premature stop codon, and translation termination) resulted in the knock-out of the target gene. The molecular and phenotypic characteristics of the mutant lines showed that the knock-out mutation of HvGSK1.1 improved plant growth performance under salt stress conditions and increased the thousand kernel weight of the plants grown under normal conditions. The inactivation of HvGSK1.1 enhanced BR-dependent signaling, as indicated by the results of the leaf inclination assay in the edited lines. The plant traits under investigation are consistent with those known to be regulated by BRs. These results, together with studies of other GSK3 gene members in other plant species, suggest that targeted editing of these genes may be useful in creating plants with improved agricultural traits.


Brassinosteroids , Hordeum , Brassinosteroids/pharmacology , Hordeum/genetics , Glycogen Synthase Kinase 3/genetics , Salt Tolerance/genetics , Signal Transduction , Plant Growth Regulators
6.
J Psychiatr Res ; 171: 152-160, 2024 Mar.
Article En | MEDLINE | ID: mdl-38281465

The present study had the following aims: 1) to compare gut microbiota composition in patients with schizophrenia and controls and 2) to investigate the association of differentially abundant bacterial taxa with markers of inflammation, intestinal permeability, lipid metabolism, and glucose homeostasis as well as clinical manifestation. A total of 115 patients with schizophrenia during remission of positive and disorganization symptoms, and 119 controls were enrolled. Altogether, 32 peripheral blood markers were assessed. A higher abundance of Eisenbergiella, Family XIII AD3011 group, Eggerthella, Hungatella, Lactobacillus, Olsenella, Coprobacillus, Methanobrevibacter, Ligilactobacillus, Eubacterium fissicatena group, and Clostridium innocuum group in patients with schizophrenia was found. The abundance of Paraprevotella and Bacteroides was decreased in patients with schizophrenia. Differentially abundant genera were associated with altered levels of immune-inflammatory markers, zonulin, lipid profile components, and insulin resistance. Moreover, several correlations of differentially abundant genera with cognitive impairment, higher severity of negative symptoms, and worse social functioning were observed. The association of Methanobrevibacter abundance with the level of negative symptoms, cognition, and social functioning appeared to be mediated by the levels of interleukin-6 and RANTES. In turn, the association of Hungatella with the performance of attention was mediated by the levels of zonulin. The findings indicate that compositional alterations of gut microbiota observed in patients with schizophrenia correspond with clinical manifestation, intestinal permeability, subclinical inflammation, lipid profile alterations, and impaired glucose homeostasis. Subclinical inflammation and impaired gut permeability might mediate the association of gut microbiota alterations with psychopathological symptoms and cognitive impairment.


Gastrointestinal Microbiome , Schizophrenia , Humans , Inflammation , Glucose , Lipids
9.
BMC Vet Res ; 19(1): 281, 2023 Dec 20.
Article En | MEDLINE | ID: mdl-38124157

BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids.  The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography. RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions. CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.


Cat Diseases , Inflammatory Bowel Diseases , Microbiota , Cats , Animals , Fatty Acids/analysis , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , Fatty Acids, Volatile/analysis , Inflammatory Bowel Diseases/veterinary , Feces/microbiology
10.
Clin Med Insights Oncol ; 17: 11795549231206796, 2023.
Article En | MEDLINE | ID: mdl-38023290

Background: Microbiome dysbiosis plays a role in the pathogenesis of many urological diseases, including bladder cancer (BC). The aim of the study was to compare the urinary and gut microbiota of patients with BC with a healthy control (HC) group. Methods: The study group included patients hospitalized in 2020 to 2021 with diagnosed BC and HC. Prior to the transurethral resection of bladder tumor, patients collected their urine and stool which was then subjected to 16S rRNA gene sequencing. Results: Overall, 25 patients were enrolled in the study: 18 in the BC group and 7 in the HC group. Analysis of the urine and stool microbiome showed no statistically significant differences between patients with BC and HC in alpha diversity, beta diversity, and difference in taxa relative abundance. Detailed analysis of urine and stool microbiome depending on patient- and tumor-related characteristics also showed no statistically significant differences in alpha diversity and beta diversity. Differences in abundance (ANCOM) were noted in both types of samples in patients with BC. In the urine test, genus Lactobacillus was more common in patients with a positive history of Bacillus Calmette-Guérin (BCG) therapy, while genus Howardella and the strain Streptococcus anginosus were more common in women. In stool samples, abundance of phylum Desulfobacterota was most abundant in Grade G1 and least in G2. Class Alphaproteobacteria, order Rhodospirillales, order Flavobacteriales, and family Flavobacteriaceae were more common in women. Conclusions: The microbiome of urine and stool of patients with BC does not differ significantly from that of HC; however, its composition in patients with BC varies according to the patient's sex.

11.
Gut Microbes ; 15(2): 2274126, 2023 Dec.
Article En | MEDLINE | ID: mdl-37979154

Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.


Gastrointestinal Microbiome , Multiple Sclerosis , Probiotics , Humans , Gastrointestinal Microbiome/physiology , Multiple Sclerosis/therapy , Probiotics/therapeutic use , Fecal Microbiota Transplantation , Diet , Dysbiosis , Prebiotics
12.
J Psychiatr Res ; 165: 298-304, 2023 09.
Article En | MEDLINE | ID: mdl-37552919

Schizophrenia is a multi-systemic disorder that is associated with lipid profile disturbances, altered glucose homeostasis and subclinical inflammation. It has been proposed that dysfunction of the gut-brain axis might underlie these alterations. Short-chain fatty acids (SCFAs) are considered to play a pivotal role in the gut-brain axis. In this study, we aimed to compare fecal levels of SCFAs in patients with schizophrenia and healthy controls (HCs), taking into consideration their relationship with common peripheral blood alterations observed in schizophrenia. The study included 100 stable outpatients with schizophrenia and 55 HCs. The levels of SCFAs (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and lactic acid) in fecal samples were measured. Also, lipid profile together with the levels of C-reactive protein, glucose and insulin were determined. The levels of isovaleric acid were significantly higher in patients with schizophrenia after co-varying for age, sex, and the adherence to the Mediterranean diet. Moreover, there were significant positive correlations of the levels of valeric acid, isovaleric acid and CRP in patients with schizophrenia. In this group of participants, higher levels of isovaleric acid were associated with significantly lower scores of delayed memory after adjustment for potential covariates and interactions with CRP levels. Our results indicate that individuals with schizophrenia show altered levels of isovaleric acid that might be associated with impairments of delayed memory. The association with cognitive impairments might be independent of interactions with immune-inflammatory processes. Longitudinal and experimental studies are needed to test causal mechanisms of observed correlations.


Gastrointestinal Microbiome , Schizophrenia , Humans , Schizophrenia/complications , Fatty Acids, Volatile/metabolism , Feces , Inflammation , Cognition
13.
Article En | MEDLINE | ID: mdl-37473955

BACKGROUND: Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). METHODS: A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples. RESULTS: Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants. CONCLUSION: Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation.


Gastrointestinal Microbiome , Schizophrenia , Humans , Gastrointestinal Microbiome/genetics , Schizophrenia/microbiology , Case-Control Studies , Glucose , Clostridiales
14.
Psychoneuroendocrinology ; 155: 106335, 2023 09.
Article En | MEDLINE | ID: mdl-37467542

Specific mechanisms underlying gut microbiota alterations in schizophrenia remain unknown. We aimed to compare gut microbiota between patients with schizophrenia and controls, taking into consideration exposure stress across lifespan, dietary habits, metabolic parameters and clinical manifestation. A total of 142 participants, including 89 patients with schizophrenia and 52 controls, were recruited. Gut microbiota were analyzed using the 16 S rRNA sequencing. Additionally, biochemical parameters related to glucose homeostasis, lipid profile and inflammation were assessed. Increased abundance of Lactobacillus and Limosilactobacillus as well as decreased abundance of Faecalibacterium and Paraprevotella were found in patients with schizophrenia. The machine learning analysis demonstrated that between-group differences in gut microbiota were associated with psychosocial stress (a history of childhood trauma, greater cumulative exposure to stress across lifespan and higher level of perceived stress), poor nutrition (lower consumption of vegetables and fish products), lipid profile alterations (lower levels of high-density lipoproteins) and cognitive impairment (worse performance of attention). Our findings indicate that gut microbiota alterations in patients with schizophrenia, including increased abundance of lactic acid bacteria (Lactobacillus and Limosilactobacillus) and decreased abundance of bacteria producing short-chain fatty acids (Faecalibacterium and Paraprevotella) might be associated with exposure to stress, poor dietary habits, lipid profile alterations and cognitive impairment.


Gastrointestinal Microbiome , Schizophrenia , Animals , Inflammation , Lipids , RNA, Ribosomal, 16S/genetics
15.
Sci Rep ; 13(1): 8603, 2023 05 26.
Article En | MEDLINE | ID: mdl-37237003

It is widely believed that microorganisms belonging to L. casei group can have positive effects on the human body. Therefore, these bacteria are used in many industrial processes, including the production of dietary supplements and probiotic preparations. When using live microorganisms in technological processes, it is important to use those without phage sequences within their genomes that can ultimately lead to lysis of the bacteria. It has been shown that many prophages have a benign nature, meaning that they don't directly lead to lysis or inhibit microbial growth. Moreover, the presence of phage sequences in the genomes of these bacteria increases their genetic diversity, which may contribute to easier colonization of new ecological niches. In the 439 analyzed genomes of the L. casei group, 1509 sequences of prophage origin were detected. The average length of intact prophage sequences analyzed was just under 36 kb. GC content of tested sequences was similar for all analyzed species (44.6 ± 0.9%). Analyzing the protein coding sequences collectively, it was found that there was an average of 44 putative ORFs per genome, while the ORF density of all phage genomes varied from 0.5 to 2.1. The average nucleotide identity calculated on sequence alignments for analyzed sequences was 32.7%. Of the 56 L. casei strains used in the next part of the study, 32 did not show culture growth above the OD600 value of 0.5, even at a mitomycin C concentration of 0.25 µg/ml. Primers used for this study allowed for the detection of prophage sequences for over 90% of tested bacterial strains. Finally, prophages of selected strains were induced using mitomycin C, phage particles were isolated and then genomes of viruses obtained were sequenced and analyzed.


Bacteriophages , Prophages , Humans , Mitomycin/pharmacology , Bacteriophages/genetics , Bacteria/genetics , Genetic Variation , Genome, Bacterial
16.
Lab Invest ; 103(8): 100177, 2023 08.
Article En | MEDLINE | ID: mdl-37207705

Two accepted possible pathways for Merkel cell carcinoma (MCC) pathogenesis include the clonal integration of the Merkel cell polyomavirus (MCPyV) into the neoplastic cells and by UV irradiation. We hypothesize that, in UV etiology, the expression of genes associated with epithelial-mesenchymal transition (EMT) would be higher in MCPyV-negative MCCs. We compared RNA expression in 16 MCPyV-negative with that in 14 MCPyV-positive MCCs in 30 patients using NanoString panel of 760 gene targets as an exploratory method. Subsequently, we confirmed the findings with a publicly available RNA sequencing data set. The NanoString method showed that 29 of 760 genes exhibited significant deregulation. Ten genes (CD44, COL6A3, COL11A1, CXCL8, INHBA, MMP1, NID2, SPP1, THBS1, and THY1) were part of the EMT pathway. The expression of CDH1/E-cadherin, a key EMT gene, and TWIST1, regulator gene of EMT, was higher in MCPyV-negative tumors. To further investigate the expression of EMT genes in MCPyV-negative MCCs, we analyzed publicly available RNA sequencing data of 111 primary MCCs. Differential expression and gene set enrichment analysis of 35 MCPyV-negative versus 76 MCPyV-positive MCCs demonstrated significantly higher expression of EMT-related genes and associated pathways such as Notch signaling, TGF-ß signaling, and Hedgehog signaling, and UV response pathway in MCPyV-negative MCCs. The significance of the EMT pathway in MCPyV-negative MCCs was confirmed independently by a coexpression module analysis. One of the modules (M3) was specifically activated in MCPyV-negative MCCs and showed significant enrichment for genes involved in EMT. A network analysis of module M3 revealed that CDH1/E-cadherin was among the most connected genes (hubs). E-cadherin and LEF1 immunostains demonstrated significantly more frequent expression in MCPvV-negative versus MCPyV-positive tumors (P < .0001). In summary, our study showed that the expression of EMT-associated genes is higher in MCPyV-negative MCC. Because EMT-related proteins can be targeted, the identification of EMT pathways in MCPyV-negative MCCs is of potential therapeutic relevance.


Carcinoma, Merkel Cell , Merkel cell polyomavirus , Polyomavirus Infections , Skin Neoplasms , Tumor Virus Infections , Humans , Carcinoma, Merkel Cell/genetics , Carcinoma, Merkel Cell/metabolism , Carcinoma, Merkel Cell/pathology , Skin Neoplasms/metabolism , Merkel cell polyomavirus/genetics , Tumor Virus Infections/complications , Tumor Virus Infections/genetics , Polyomavirus Infections/complications , Polyomavirus Infections/genetics , Epithelial-Mesenchymal Transition/genetics , Hedgehog Proteins , Cadherins
17.
Psychoneuroendocrinology ; 153: 106109, 2023 07.
Article En | MEDLINE | ID: mdl-37075652

There is evidence that subclinical inflammation and increased gut permeability might be involved in the pathophysiology of schizophrenia. Less is known about these phenomena in patients with the deficit subtype of schizophrenia (D-SCZ) characterized by primary and enduring negative symptoms. Therefore, in the present study we aimed to compare the levels of zonulin (the marker of gut permeability) and immune-inflammatory markers in patients with D-SCZ, those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). A total of 119 outpatients with schizophrenia and 120 HCs were enrolled. The levels of 26 immune-inflammatory markers and zonulin were determined in serum samples. The following between-group differences were significant after adjustment for multiple testing and the effects of potential confounding factors: 1) higher levels of interleukin(IL)- 1ß and C-reactive protein (CRP) in patients with D-SCZ compared to those with ND-SCZ and HCs; 2) higher levels of tumor necrosis factor-α and RANTES in both groups of patients with schizophrenia compared to HCs and 3) higher levels of IL-17 in patients with D-SCZ compared to HCs. No significant between-group differences in zonulin levels were found. Higher levels of IL-1ß and CRP were associated with worse performance of attention after adjustment for age, education and chlorpromazine equivalents. Also, higher levels of IL-1ß were correlated with greater severity of negative symptoms after adjustment for potential confounding factors. In conclusion, individuals with D-SCZ are more likely to show subclinical inflammation. However, findings from the present study do not support the hypothesis that this phenomenon is secondary to increased gut permeability.


Schizophrenia , Humans , Case-Control Studies , Biomarkers , C-Reactive Protein , Inflammation , Phenotype
18.
Genes (Basel) ; 14(4)2023 03 24.
Article En | MEDLINE | ID: mdl-37107547

The number of people suffering from metabolic syndrome (MetS) including type 2 diabetes (T2DM), hypertension, and obesity increased over 10 times through the last 30 years and it is a severe public health concern worldwide. Uncoupling protein 1 (UCP1) is a mitochondrial carrier protein found only in brown adipose tissue involved in thermogenesis and energy expenditure. Several studies showed an association between UCP1 variants and the susceptibility to MetS, T2DM, and/or obesity in various populations; all these studies were, however, limited to a few selected polymorphisms. The present study aimed to search within the entire UCP1 gene for new variants potentially associated with MetS and/or T2DM risk. We performed NGS sequencing of the entire UCP1 gene in 59 MetS patients including 29 T2DM patients, and 36 controls using the MiSeq platform. An analysis of allele and genotype distribution revealed nine variations which seem to be interesting in the context of MetS and fifteen in the context of T2DM. Altogether, we identified 12 new variants, among which only rs3811787 was investigated previously by others. Thereby, NGS sequencing revealed new intriguing UCP1 gene variants potentially associated with MetS and/or T2DM risk in the Polish population.


Diabetes Mellitus, Type 2 , Metabolic Syndrome , Humans , Metabolic Syndrome/genetics , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolism , Diabetes Mellitus, Type 2/genetics , Poland , Obesity/genetics
19.
Pharmaceutics ; 15(2)2023 Jan 28.
Article En | MEDLINE | ID: mdl-36839755

In recent years, multidrug-resistant (MDR) strains of Klebsiella pneumoniae have spread globally, being responsible for the occurrence and severity of nosocomial infections. The NDM-1-kp, VIM-1 carbapenemase-producing isolates as well as extended-spectrum beta lactamase-producing (ESBL) isolates along with Klebsiella oxytoca strains have become emerging pathogens. Due to the growing problem of antibiotic resistance, bacteriophage therapy may be a potential alternative to combat such multidrug-resistant Klebsiella strains. Here, we present the results of a long-term study on the isolation and biology of bacteriophages active against K. pneumoniae, as well as K. oxytoca strains. We evaluated biological properties, morphology, host specificity, lytic spectrum and sensitivity of these phages to chemical agents along with their life cycle parameters such as adsorption, latent period, and burst size. Phages designated by us, vB_KpnM-52N (Kpn52N) and VB_KpnM-53N (Kpn53N), demonstrated relatively broad lytic spectra among tested Klebsiella strains, high burst size, adsorption rates and stability, which makes them promising candidates for therapeutic purposes. We also examined selected Klebsiella phages from our historical collection. Notably, one phage isolated nearly 60 years ago was successfully used in purulent cerebrospinal meningitis in a new-born and has maintained lytic activity to this day. Genomic sequences of selected phages were determined and analyzed. The phages of the sequenced genomes belong to the Slopekvirus and Jiaodavirus genus, a group of phages related to T4 at the family level. They share several features of T4 making them suitable for antibacterial therapies: the obligatorily lytic lifestyle, a lack of homologs of known virulence or antibiotic resistance genes, and a battery of enzymes degrading host DNA at infection.

20.
Acta Neuropsychiatr ; 35(3): 147-155, 2023 Jun.
Article En | MEDLINE | ID: mdl-36503629

OBJECTIVE: The pathogenesis of schizophrenia is multidimensional and intensively studied. The gut-brain axis disturbances might play a significant role in the development of schizophrenia. METHODS: We compared the gut microbiota of 53 individuals with schizophrenia and 58 healthy controls, using the 16S rRNA sequencing method. Individuals with schizophrenia were assessed using the following scales: the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Social and Occupational Functioning Assessment Scale and the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: No significant between-group differences in α-diversity measures were observed. Increased abundance of Lactobacillales (order level), Bacilli (class level) and Actinobacteriota (phylum level) were found in individuals with schizophrenia regardless of potential confounding factors, and using two independent analytical approaches (the distance-based redundancy analysis and the generalised linear model analysis). Additionally, significant correlations between various bacterial taxa (the Bacteroidia class, the Actinobacteriota phylum, the Bacteroidota phylum, the Coriobacteriales order and the Coriobacteria class) and clinical manifestation (the severity of negative symptoms, performance of language abilities, social and occupational functioning) were observed. CONCLUSIONS: The present study indicates that gut microbiota alterations are present in European patients with schizophrenia. The abundance of certain bacterial taxa might be associated with the severity of negative symptoms, cognitive performance and general functioning. Nonetheless, additional studies are needed before the translation of our results into clinical practice.


Gastrointestinal Microbiome , Schizophrenia , Humans , Schizophrenia/diagnosis , Outpatients , Case-Control Studies , RNA, Ribosomal, 16S/genetics
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