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Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats
No full textThe anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund’s adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect
Polne specifičnosti u modulatornom delovanju noradrenalina na CD4+ t-limfocite u modelu eksperimentalnog autoimunskog encefalomijelitisa
No full textIt has been hypothesized that dysfunction in, basically sexually dimorphic, activity of the sympathetic nervous system (SNS) contributes to the pathogenesis of experimental autoimmune encephalomyelitis (EAE). To test the hypothesis, the influence of pharmacological manipulations with action of noradrenaline (end point mediator of the SNS) on CD4+ T-cells in draining lymph nodes (dLNs) and CD4+ T-cell-mediated inflammation in the spinal cord (SC) of female and male Dark Agouti (DA) rats immunized for EAE was investigated. Since blockade of β-adrenoceptors (ARs), but not α-ARs, produced sexually dimorphic effects, study was focused on the effects of β-AR blockade. In vivo blockade of β-AR with propranolol (PROP) over the peri-inductive/inductive phase of EAE decreased dLN CD4+ T-cell proliferation and differentiation into potentially pathogenic cells regardless of sex. This reflected the net effect of sex-specific (greater in males) PROP-induced (a) inhibition of antigen presenting cell (APC) migration in vivo, and (b) stimulation of IL-1β and IL-23 expression in APCs, and CD4+ cell proliferation and differentiation into potentially highly pathogenic IL-17+GM-CSF+ cells, observed in vitro. PROP treatment in the effector phase of EAE promoted anti-inflammatory phenotype of microglia by direct or indirect (via CX3CL1/CX3CR1 pathway stimulation) transcriptional activation of Nrf2/HO-1 axis and inhibitory action on IL-6/Stat3 axis components expression (partly via upregulation of Socs3), and thereby decreased SC infiltration with blood-borne myeloid cells and CD4+ T-cells, and their reactivation and differentiation into IL-17+GM-CSF+ cells. Effects of PROP were more prominent in male than female rats, partly explaining greater decrease in EAE severity in PROP-treated males.Pretpostavljeno je da disfunkcija u, suštinski polno dimorfnoj, aktivnosti simpatičkog nervnog sistema (SNS) doprinosi patogenezi eksperimentalnog autoimunskog encefalomijelitisa (EAE). Ova hipoteza je testirana ispitivanjem uticaja farmakoloških manipulacija delovanjem noradrenalina (krajnji medijator SNS), na CD4+ T-limfocite u drenirajućim limfnim čvorovima (dLČ) i na inflamaciju posredovanu CD4+ T-limfocitima u kičmenoj moždini (KM) ženki i mužjaka pacova soja Dark Agouti (DA) kod kojih je indukovan EAE. Kako je blokada β-adrenalinskih receptora (AR), ali ne i α-AR, pokazala polno dimorfne efekte, istraživanje je bilo usmereno na efekte blokade β-AR. In vivo blokada β-AR propranololom (PROP) u peri-induktivnoj/induktivnoj fazi EAE smanjila je proliferaciju CD4+ T-limfocita i njihovu diferencijaciju u potencijalno patogene ćelije u dLČ nezavisno od pola. Ovakav efekat je rezultanta polno-specifičnog (izraženijeg kod mužjaka) (a) inhibitornog delovanja PROP na migraciju antigen-prezentujućih ćelija (APĆ) in vivo, i (b) stimulativnog efekta PROP na ekspresiju IL-1β i IL-23 u APĆ, te proliferaciju i diferencijaciju CD4+ limfocita u potencijalno visoko patogene IL-17+GM-CSF+ ćelije, uočenog in vitro. Tretman PROP u efektorskoj fazi EAE je stimulisao razvoj anti-inflamatornog fenotipa mikroglije, direktnom ili indirektnom (stimulacijom CX3CL1/CX3CR1 signalnog puta) transkripcionom aktivacijom Nrf2/HO-1 osovine, i inhibitornim delovanjem na komponente IL-6/Stat3 osovine (delom kroz ushodnu regulaciju ekspresije Socs3), i time smanjio infiltraciju KM mijeloidnim ćelijama i CD4+ T-limfocitima, i njihovu reaktivaciju i diferencijaciju u IL-17+GM-CSF+ ćelije. Ovi efekti PROP su bili izraženiji kod mužjaka nego ženki pacova, objašnjavajući, delom, izraženije smanjenje težine EAE kod pacova muškog pola
Influence of cultivation method on M. bovis pasteur 1173p2 fatty acid and protein content – preliminary results
No full textBCG vaccine is one of the most widely used vaccines, effectively preventing tuberculosis (TB) in
infants. Since the 70s Mycobacterium bovis BCG
str, Pasteur 1173P2 has been used to vaccinate
newborns in Serbia. In this study, we present fatty acid (FA) analysis and protein content of differently cultivated M. bovis 1173P2. M. bovis was cultivated in two growth media, the Sauton liquid
media pellicle growth method and cultivation in
Middlebrook media supplemented with OADC.
FA was extracted using chloroform/methanol
(2:1 v/v) and after direct trans-esterification FAs
were analyzed using gas chromatography. Proteins were extracted by homogenizing the bacterial pellet in 1% sodium dodecyl sulfate/protease inhibitors, followed by centrifugation and
methanol-chloroform precipitation. Proteomics
analysis was performed by in-gel trypsin digestion followed by label-free relative quantification
on a nano LC-ESI-MS/MS system. Cultivation in
Sauton media gave higher levels of FA 14:0, 18:0,
18:1n-9, 18:3n-6 and 20:3; higher peroxidability
index and lower levels of 15:0, 16:1, 17:0, 19:0,
18:2 compared to Middlebrook OADC. A total
of 335 proteins were identified which showed
>60% reduced expression in Middlebrook OADC
media (including probable fatty acid synthase, a
mycocerosic acid synthase and a putative thiosulfate sulfurtransferase), and 199 proteins with
>60% increased expression (including probable
oxidoreductase, a double hotdog hydratase and
probable short-chain dehydrogenase). Numerous differences in cell constituents upon cultivation of M. bovis in two different liquid media
infer that transfer from the classical cultivation in
Sauton liquid media to fermentation production
in Middlebrook OADC would require immunogenicity testing and/or dose adjustment
A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo
No full textInfections caused by multidrug-resistant pathogens are one of the biggest challenges facing the healthcare system today. Quorum quenching (QQ) enzymes have the potential to be used as innovative enzyme-based antivirulence therapeutics to combat infections caused by multidrug-resistant pathogens. The main objective of this research was to describe the novel YtnP lactonase derived from the clinical isolate Stenotrophomonas maltophilia and to investigate its antivirulence potential against multidrug-resistant Pseudomonas aeruginosa MMA83. YtnP lactonase, the QQ enzyme, belongs to the family of metallo-β-lactamases. The recombinant enzyme has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic effect. High-performance liquid chromatography analysis revealed the activity of recombinant YtnP lactonase toward a wide range of N-acyl-homoserine lactones (AHLs), quorum sensing signaling molecules, with a higher preference for long-chain AHLs. Recombinant YtnP lactonase was shown to inhibit P. aeruginosa MMA83 biofilm formation, induce biofilm decomposition, and reduce extracellular virulence factors production. Moreover, the lifespan of MMA83-infected Caenorhabditis elegans was prolonged with YtnP lactonase treatment. YtnP lactonase showed synergistic inhibitory activity in combination with gentamicin and acted additively with meropenem against MMA83. The described properties make YtnP lactonase a promising therapeutic candidate for the development of next-generation antivirulence agents
Supplementary Material for: Patiño-Guillén, G.; Pešović, J.; Panić, M.; Savić-Pavićević, D.; Bošković, F.; Keyser, U. F. Single-Molecule RNA Sizing Enables Quantitative Analysis of Alternative Transcription Termination. Nat Commun 2024, 15 (1), 1699. https://doi.org/10.1038/s41467-024-45968-8.
No full textThis PDF file includes: → Supplementary Figures 1 to 29 → Supplementary Tables 1 to 8Related to the published version: [https://intor.torlakinstitut.com/handle/123456789/865]Supplementary material for: [https://doi.org/10.17863/CAM.104528
Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions
No full textDiphtheria and tetanus, once formidable causes of morbidity and mortality worldwide, have seen their threats markedly diminished through the advent and widespread use of vaccines. This review article delves into the historical journey of diphtheria and tetanus vaccines, evaluates their current status in global immunization programs, and explores future perspectives in their evolution and implementation. The inception of diphtheria and tetanus vaccines marked a pivotal shift in infectious disease control. The development of diphtheria toxoid by Emil von Behring in the late 19th century and the subsequent creation of tetanus toxoid in the early 20th century set the stage for large-scale immunization efforts. These efforts were bolstered in the mid-20th century with the integration of these toxoids into combination vaccines, notably the DTP (diphtheria-tetanus-pertussis) vaccine, facilitating broader immunization coverage and enhanced public health outcomes. Currently, the inclusion of diphtheria and tetanus vaccines in national immunization schedules has led to a significant decline in the incidence of these diseases globally. However, challenges remain, including disparities in vaccine coverage and the emergence of non-toxigenic strains causing diphtheria. The review highlights the WHO’s strategies towards achieving higher immunization coverage and the importance of maintaining high vaccination rates to prevent resurgence. Looking forward, the review discusses the ongoing research and development aimed at improving vaccine formulations, reducing adverse reactions, and enhancing the efficacy and durability of protection. Innovations such as nanoparticle vaccines and DNA vaccines are explored as potential avenues for future advancements. Additionally, the review addresses the critical role of global health governance in addressing vaccine hesitancy, improving access in low-resource settings, and coordinating responses to outbreaks. In conclusion, while the battle against diphtheria and tetanus has seen significant victories, continuous efforts in vaccine innovation, policy implementation, and global cooperation are essential to sustain these gains and achieve the ultimate goal of global eradication
Impact of the COVID‐19 Pandemic on Influenza Circulation During the 2020/21 and 2021/22 Seasons, in Europe
No full textBackground: The emergence of SARS‐CoV‐2 in late 2019 saw the implementation of public health and social measures (PHSM) by countries across Europe to reduce its transmission and impact on populations. Consequently, countries reported changes in influenza circulation and extensive disruptions to routine surveillance systems.MethodsWe describe the epidemiology of influenza in Europe between Weeks 40/2020 and 39/2022 compared to the 2016/17 to 2019/20 seasons, to assess the impact of the COVID‐19 pandemic and PHSM on surveillance systems and influenza circulation.ResultsLow detections of influenza were observed through primary care sentinel sources during seasonal influenza periods (Week 40 to 20); 56 (of 39,457 specimens tested; < 1% positivity) in 2020/21 and 7261 (of 64,153 specimens tested; 11% positivity) detections in 2021/22 were observed, compared to an average of 18,383 (of 50,544 specimens tested; 36% positivity) detections in 2016/17 to 2019/20. Similarly, 11 (of 19,989 specimens tested; < 1% positivity) and 1488 (of 23,636 specimens tested; 6% positivity) detections were reported through SARI surveillance sources in 2020/21 and 2021/22, respectively, compared to an average of 2850 (of 10,389 specimens tested; 27% positivity) detections in 2016/17 to 2019/20. However, the 2021/22 interseasonal period saw unusual increases in influenza detections across surveillance site types when PHSM were easing.ConclusionIn conclusion, findings suggest that the restriction and easing of PHSM measures were associated with variations in influenza detections. Our observations of out‐of‐season influenza activity highlight the importance of an integrated respiratory surveillance strategy to monitor circulating respiratory viruses throughout the year to inform optimal prevention and control strategies.Data Availability Statement TESSy data are available upon request ([https://www.ecdc.europa.eu/ en/publications-data/european-surveillance-system-tessy])
Can Lacticaseibacillus rhamnosus modulate the immune response to inactivated Influenza vaccine in young and old rats?
No full textPurpose: The senescence of the immune system bears the burden of poor response to vaccination. The Influenza virus is
a common etiological factor that humans encounter every year. The elderly are at greater risk of undesirable outcomes,
even when vaccinated, since the vaccine response rate is 45-65%. To address the poor immunological response to
vaccination in the elderly, we sought a non-invasive and comfortable “adjuvant” in the form of probiotic
Lacticaseibacillus rhamnosus that could boost the immune response and affect the vaccination outcomes.
Methods: Young (3) and old (24 months) Dark Agouti female rats were set into four experimental groups (n=6). One
from each group of young and old rats received L.rhamnosus supplemented to the water (⁓1x109 CFU per day) 7 days
before the vaccination and during the next 3 weeks after it (L.rhamnosus+vaccinated). The control groups drank tap water
ad libitum (control+vaccinated). All 4 groups were vaccinated with the seasonal Influenza vaccine (inactivated,
fragmented virus). Three weeks after the vaccination, the experiment was ended and the thymuses and blood were
retrieved for flow cytometry, qPCR, and ELISA analysis.
Results: Our results indicated that supplementation with L.rhamnosus induced a significant increase (p<0.05) in the
frequency of Foxp3+CD25+CD4+TCRαβ+ cells in the blood of young, but not old vaccinated rats. Also, their thymuses
were significantly (p<0.05) larger compared to the control vaccinated group of the same age. Following this was the
significantly lower (p<0.05) frequency of memory CD90-CD45RC-CD4+ T cells in the blood of the young
L.rhamnosus+vaccinated group and CD28nullCD8+ T cells (p<0.05) in both young and old L.rhamnosus+vaccinated
groups compared to the control group. Interestingly, the concentration of proinflammatory IFNγ was significantly lower
(p<0.01) in sera retrieved from both young and old vaccinated rats that received L.rhamnosus supplementation.
Conclusion: The immunomodulatory effect of L.rhamnosus is complex and affects both primary and secondary lymphoid
systems. Our preliminary results suggest that L.rhamnosus supplementation: can be beneficial to vaccination outcomes
for both young and old but is guided by different mechanisms; it could potentially affect slower thymus involution and
take part in postponing the immunosenescence. Future experiments should provide us with additional answers
rBet v 1a-BanLecwt induce upregulation of IL-10 and IFN-γ gene expression in Caco-2/THP-1 co-culture and secretion of IL-10 and IFN-γ/IL-4 levels in PBMCs of birch pollen allergic donors
No full textNovel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT
Supplementary information for the article: Virijević, K.; Živanović, M. N.; Nikolić, D.; Milivojević, N.; Pavić, J.; Morić, I.; Šenerović, L.; Dragačević, L.; Thurner, P. J.; Rufin, M.; Andriotis, O. G.; Ljujić, B.; Miletić Kovačević, M.; Papić, M.; Filipović, N. AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing. ACS Appl. Mater. Interfaces 2024. https://doi.org/10.1021/acsami.4c03266.
No full textFigure S1. Publication Trends in “Electrospinning”, “Electrospinning + PCL + PEG”, “Electrospinning + Wound Healing” and “Electrospinning + Artificial Intelligence + Neural Network” Research (2001-2022) Table S1. Synonyms and Related Terms for Electrospinning in Research (2001-2022) Table S2. Input data structured for ANN – CSV data file Figure S2. Basic visualization of the dependence of output data (vertical axis) on individual input data (horizontal axis). Figure S3. Schematic representation of the neural network Figure S4. Graph of RMSE relation between training data set (blue line) and validation data set (orange line) depending on the number of neurons in the hidden layer Figure S5. Visual representation of ANN precision; the horizontal axis represents the percent of the real result, and the vertical axis represents the percent of ANN prediction; the training set (blue dots), prediction set (orange dots) Scheme S1. Electrospinning-Ready Polymer and Solvent Combinations. “Substance” is PCL or PCL combined with PEG. The substance is dissolved in mass concentrations from 17 to 28% in CHCl3 or a combination of CHCl3 and DMF. Figure S6. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 1: PCL in CHCl3. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% J) 26% K) 27% Figure S7. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 2: PCL in CHCl3:DMF=1:1. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% J) 26% K) 27% Figure S8. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 3: PCL in CHCl3:DMF=1:3. A) 17% B) 18% C) 19% Figure S9. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 4: PCL in CHCl3:DMF=3:1. A) 17% B) 18% C) 19% D) 20% E) 21% Figure S10. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 5: PCL:PEG=1:1 in CHCl3. A) 17% B) 18% C) 20% D) 21% E) 22% F) 24% G) 25% H) 26% I) 27% J) 28% Figure S11. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 6: PCL:PEG=1:1 in CHCl3:DMF=1:1. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% J) 26% K) 27% Figure S12. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 7: PCL:PEG=1:1 in CHCl3:DMF=3:1. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% Figure S13. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 8: PCL:PEG=3:1 in CHCl3:DMF=1:1. A) 17% B) 19% C) 20% D) 21% E) 22% F) 24% G) 26% Figure S14. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 9: PCL:PEG=3:1 in CHCl3:DMF=1:3. A) 17% B) 18% C) 19% D) 22% Figure S15. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 10: PCL:PEG=3:1 in CHCl3:DMF=3:1. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% J) 26% Figure S16. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 15: PCL:PEG=1:3 in CHCl3:DMF=3:1. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% Figure S17. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 16: PCL:PEG=7:3 in CHCl3:DMF=7:3. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% G) 23% H) 24% I) 25% J) 26% K) 27% Figure S18. Fiber Diameter Distribution Analysis of Electrospun-Derived Scaffold for Series 17: PCL:PEG=3:1 in CHCl3. A) 17% B) 18% C) 19% D) 20% E) 21% F) 22% Figure S19. The action of scaffolds bearing antibiotics on selected strains of bacteria by disk diffusion method. Figure S20. Chick Embryo CAM Assay Procedure: A) Egg selection B) Egg disinfection with 10% of iodine solution C) Inoculation and preparation for scaffold insertion D) Egg’s incubation E) Daily monitoring of embryo development and possible contamination F) Sacrifice of treated embryos and fixation with 4% PFA G) CAM membrane preparation H) Image capture and evaluation of blood vesselsSupplementary material for: [https://intor.torlakinstitut.com/handle/123456789/872]Related to the published version: [https://doi.org/10.1021/acsami.4c03266