imagine (Institute of molecular genetics and genetic engineering)
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DEVELOPMENT AND CHARACTERIZATION OF NOVEL BIOBASED POLYURETHANE FILMS REINFORCED WITH BACTERIAL BIOMASS
No full textIn recent years, there has been a growing global interest in developing
sustainable and eco-friendly materials to address the depletion of fossil fuel resources
and the accumulation of non-biodegradable plastic waste. A potential strategy for
addressing these issues is replacing fossil-based feedstocks with bio-based alternatives.
Recent advancements in green polyurethane (PU) synthesis focus on using bio-based
materials such as non-edible oils and agricultural byproducts to replace diisocyanates
and polyols and create new PUs. This study explores the synthesis and characterization
of a series of novel bio-based polyurethanes (bio-PUs). The polymers were synthesized
using castor oil, mcl-PHA and bacterial biomass from PHA fermentations as bio-fillers
and hexamethylenediisocyanate (HMDI) as a crosslinking agent by solvent casting
without any catalyst. These bio-PUs were characterized by ATR-FTIR spectroscopy,
SEM, X-ray diffraction, and TG/DTG analysis. Urethane bond formation was
confirmed and their mechanical properties, transparency, swelling, and eco-toxicity
using Caenorhabditis elegans and healthy human fibroblasts cell line were evaluated
to determine their applicative potential. Notably, water contact angle measurements
revealed that bio-PU, containing spent biomass after PHA biopolymer extraction
exhibited higher hydrophobicity than other bio-PUs. Additionally, the biodegradability
of these PUs was investigated using known plastic-degrading esterases Humicola
insolens cutinase and Candida antarctica lipase B as well as PU-degrading bacterial
strains Amycolatopsis mediterranei ISP5501 and Streptomyces sp. PU10. This study
underscores the potential applicability and sustainability of castor oil, mcl-PHA, and
biomass-derived bio-PUs, presenting an exciting opportunity for the development of
innovative materials with tailored properties and reduced environmental impact.Compiled poster abstract booklet for the 19th Int’l Symposium on Biopolymers
20th-23rd October 2024
School of Biological Sciences, Universiti Sains Malaysi
DEVELOPMENT AND CHARACTERIZATION OF NOVEL BIOBASED POLYURETHANE FILMS REINFORCED WITH BACTERIAL BIOMASS
No full textIn recent years, there has been a growing global interest in
developing sustainable and eco-friendly materials to
address the depletion of fossil fuel resources and the
accumulation of non-biodegradable plastic waste. A
potential strategy for addressing these issues is replacing
fossil-based feedstocks with bio-based alternatives.
Recent advancements in green polyurethane (PU)
synthesis focus on using bio-based materials such as non-
edible oils and agricultural byproducts to replace
diisocyanates and polyols and create new PUs
9P Synergistic potential of vitamin D receptor and cancer stem cells markers expression in ovarian tumors
No full textBackground: Ovarian cancer (OC) is the most aggressive gynecological malignancy. Vitamin D actions mediated by its receptor (VDR) showed significant antitumor activity. Cancer stem cells (CSC) that are characterized by specific surface markers CD44 and CD133, are responsible for the tumor resistance to various treatment modalities. This study aimed to analyze the association of CD44, CD133, and VDR expression in epithelial ovarian tumors (EOT). Methods: Our cohort comprised 218 patients with EOT of which 131 were OC, 42 atypical proliferative tumors (APT), and 45 benign tumors. A set of histopathology parameters were correlated with CD44, CD133, and VDR immunohistochemical expressions, using the tissue microarray method. We used extensive scoring method (IR score, Remmele’s score) as a more validate than basic one. It considered multiplied staining intensity (0- absent, 1- low, 2- moderate, 3- strong) and the percentage of positive cancer cells (0 ¼ 0%, 1 10%, 2 ¼ 11e50%, 3 ¼ 51e80%, 4 81% of the cells). High expression was defined as IR score >2, while low expression was with IR score 0-2. Results: There was a positive correlation between CD44, CD133, and VDR markers in all groups (p<0.05). CD44 and cytoplasmic VDR expression showed higher levels in OC than in other groups, while CD133 expression was most prominent in the APT (p<0.05). Significant CD44 and VDR expression was evident in high grade serous carcinoma (HGSC) in advanced stages. CD133 marker did not show a correlation with these histopathology parameters. This study indicates very important and complex relationships between CSCs and VDR-mediated calcitriol function, which certainly is one of the very crucial regulation mechanisms in CSC. High VDR expression point to possible effective antitumor (calcitriol) therapy in HGSC ovarian cancer cells. Calcitriol treatment could activate the VDR signaling pathway in CSCs, which further disrupts the CSC’s stemness, leading to a reduction of the CSC population. Conclusions: Significant CD44 and cytoplasmic VDR expressions were demonstrated in ovarian CSC in aggressive types as HGSC, at advanced stages. It indicates the possible benefits of target therapy in patients with high expression levels of these markers
Tuning properties of microbial biopolymers towards biomedical applications
No full textMicrobial biopolymers, including bacterial nanocellulose (BNC) and
polyhydroxyalkanoates (PHA), have garnered increasing attention and potential in
biomedical applications due to their inherent tunable properties and biocompatibility.
These biopolymers offer unique advantages such as customizable chemical
compositions and versatile structural characteristics, which can be further optimized
through genetic, environmental, and process engineering approaches. Recent
advancements and strategies in harnessing BNC and PHA for biomedical applications,
focusing on tuning of structural properties and employing functionalization strategies,
will be highlighted.
The integration of BNC and PHA with biomolecules (such as prodigiosin and
nonactin), nanoparticles, or pharmaceutical agents has enabled the creation of tailored
functionalities essential for targeted drug delivery systems, accelerated wound healing
processes, and advanced tissue engineering constructs. Moreover, significant efforts
have been directed towards modifying the nanostructure and surface properties of BNC
and PHA to enhance mechanical resilience, expedite biodegradation rates, and improve
their compatibility with biological systems. These advancements pave the way for the
practical implementation of BNC and PHA in various biomedical devices, scaffolds for
tissue regeneration, wound dressings designed and diagnostic tools. By exploring these
innovations, the field of biomedical materials is advancing towards more effective and
sustainable solutionsAbstract booklet
for the 19th Int’l Symposium on Biopolymers
20th
-23rd October 2024
School of Biological Sciences, Universiti Sains
Malaysi
Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells
No full textAryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases
Effect of Acetylsalicylic Acid on Biological Properties of Novel Cement Based on Calcium Phosphate Doped with Ions of Strontium, Copper, and Zinc
No full textThis study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA
PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: REAL-WORLD DATA OF 7-YEAR SINGLE-CENTER EXPERIENCE SHOW MAJORITY OF PATIENTS IN POOR PERFORMANS STATUS AND POSITIVE IMPACT OF TOTAL/MAXIMAL TUMOR RESECTION ON SURVIVAL
No full textUvod: Pacijenti sa primarnim limfomom centralnog nervnog sistema (PCNSL) se
često prezentuju ograničenom pokretljivošću i lošim opštim stanjem što ih čini
nepogodnim za kliničke studije, te je rezultate takvih studija teško tumačiti u
kontekstu svakodnevne kliničke prakse.
Cilj: Prezentovati kohortu neselektovanih pacijenata sa PCNSL iz svakodnevne
kliničke prakse i analizirati njihove kliničke karakteristike, lečenje i ishod.
Metode: Sproveli smo retrospektivnu studiju na jednom centru analizirajući
podatke prikupljene iz dokumentacije 26 pacijenata koji su lečeni u periodu 2017-
2023. godine. Pacijenti sa histologijom koja nije difuzni B-krupnoćelijski limfom
nisu uzimani u obzir.
Rezultati: Dve trećine (17, 65%) su bili slabog performans statusa (PS) (ECOG
3-4/Karnofsky ≤ 50%). Dijagnoza je postavljena nakon totalne ili maksimalne
resekcije tumora kod 12 pacijenata (46%). Preživljavanje bez progresije (PFS) je
bilo značajno duže kod pacijenata bez venske tromboembolije (VTE) (p = 0,047),
pacijenata kod kojih je na dijagnozi učinjena totalna ili maksimalna resekcija tumora
(p = 0,008), kod kojih je kompletirana indukciona terapija (p < 0,001), koji
su postigli odgovor na indukcionu terapiju (p < 0,001) i koji su lečeni konsolidacijom
zračnom terapijom (RT) ili autolognom transplantacijom (ASCT) (p < 0,001).
Totalna ili maksimalna resekcija tumora (p = 0,035), kompletiranje (p < 0,001) i
postizanje odgovora na indukcionu terapiju (p < 0,001), konsolidacija RT ili ASCT
(p < 0,001) pokazali su značajan pozitivan efekat na ukupno preživljavanje.
Zaključak: Značajan broj pacijenata u svakodnevnoj kliničkoj praksi se prezentuje
slabim PS. Značajno bolji rezultati lečenja su postignuti ako je inicijalno
sprovedena opsežna operacija, odnosno ako je sistemsko lečenje bilo maksimalno
(indukcija + konsolidacija).Introduction: Patients with primary central nervous system lymphoma (PCNSL)
often present with reduced mobility and poor general condition which make
them ineligible for clinical trials, thus leading to results that cannot be extrapolate
to real-life.
Objective: To present real-world cohort of unselected PCNSL patients and their
clinical and laboratory features, treatment and outcome.
Methods: We conducted single-center retrospective study analysing real-world
data from 26 patients managed from 2017 to 2023. Patients with histology other
than diffuse large B-cell lymphoma were excluded from the study.
Results: Two thirds (17 patients, 65%) presented with poor performance status
(PS) (ECOG 3-4/ Karnofsky index ≤ 50%). Diagnosis was made after total tumor
extirpation or maximal resection in 12 patients (46%). Progression-free survival
was significantly prolonged in patients without VTE (p = 0.047), patients who
experienced diagnostic total or maximal tumor resection (p = 0.008), in those
who completed induction treatment (p < 0.001), who achieved response after
induction treatment (p < 0.001) and received consolidative radiotherapy (RT) or
autologous stem cell transplant (ASCT) (p < 0.001). Total or maximal tumor resection
(p = 0.035), completion (p < 0.001) and response to induction treatment
(p < 0,001), consolidative RT or ASCT (p < 0.001) showed significant positive impact
on overall survival.
Conclusion: Significant number of patients in real-world setting are in poor
PS. In our cohort survival was significantly affected by VTE, total/maximal tumor
resection, completion and achievement of CR/PR to induction treatment,
and consolidation. Larger real-world databases are warranted for more reliable
conclusions.Abstract book: Nacionalni kongres, 6. KONGRES HEMATOLOGA SRBIJE, Crowne Plaza, Beograd
17–19. oktobar 2024. godin
CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES ASSOCIATED WITH EPILEPSY
No full textChildhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% of the
origins of epilepsy can be attributed to genetic factors. The application of next-generation sequencing has
revolutionized molecular diagnostics and has enabled identification of disease-causing genes and variants
in childhood epilepsies. In our study, 55 children with epilepsy of unknown etiology were analyzed
combining clinical-exome and whole-exome sequencing. Molecular genetic cause of epilepsy was
identified in 31 patients and the overall diagnostic success rate was 56%. We identified variants in 23
different genes associated with epilepsy that correlate well with the observed phenotype. This includes
genes such as ASH1L, CILK1, KCNMA1, RHOBTB2 and SLC13A5, which have only recently been
associated with epilepsy. Half (51.6%) of solved patients carried novel variants. These sixteen novel
variants were characterized using various in silico algorithms including Phyre2, EzMol, Aminode and
MutPred2 for structure prediction. Interestingly, identification of a causative gene directed attention to
15 individuals, including six individuals who carry entirely novel genetic variants, for whom therapeutic
options may be available (ALDH7A1, GRIN1, KCNQ2, PNPO, SCN1A and SCN2A). Described novel
variants will contribute to better understanding of the European genetic landscape, while insights on
genotype-phenotype correlation will contribute to better understanding of childhood epilepsies around
the globe. Given the expansion of molecular-based approaches, each newly identified genetic variant
could become a potential therapeutic target.Book of abstracts: 2nd B&H Symposium of Laboratory Geneticists and Molecular Biologists (with International Participation) May, 202
TUMOR NECROSIS FACTOR ALPHA GENE POLYMORPHISMS -238G˃A AND -308G˃A AS GENETIC MARKERS FOR THE DEVELOPMENT OF ALCOHOL RELATED LIVER CIRRHOSIS
No full textAlcohol-related liver cirrhosis (ALC) is a progressive liver disease that may result
from excessive alcohol abuse. Endotoxemia induced by ethanol consumption represents a strong stimulus
for Kupffer cells to secrete Tumor necrosis factor-α (TNF-α). TNF-α induces an inflammatory response
that often leads to chronic liver injury. It plays a key role in the pathogenesis of alcohol-related liver
disease. Our study aimed to estimate the association of ΤNF-α promoter polymorphisms at two positions
(-238G˃A and -308G˃A) with ALC susceptibility from one group of ALC patients from Serbia. A total
of 118 patients with ALC and 131 sex and age-matched healthy controls were clinically examined and
genetically tested. DNA was extracted from peripheral blood lymphocytes, and genotyping was
performed using PCR-RFLP for both promoter variants. We determined the TNF-α genotypes of each
participant by the presence of the relevant DNA fragments on agarose gel. Groups were compared using
the Chi-Square test; binary logistic regression was used to obtain odds ratios. Concerning the -238G>A
variant, a significant association between A allele carriers and risk of ALC (OR=2.36, 95% CI=1.15-
4.83; p=0.019) was observed. We found only one patient with an AA genotype, so we compared the
combined AA and GA genotypes with GG genotype. No significant differences were found in either
genotype or allelic frequencies of the –308 TNF-α gene variant between the patients and controls (allele
frequencies 15.7% vs. 13.4%, p=0.463). The -238 TNF-α –A allele was associated with a higher risk of
developing ALC in our group of patients with ALC from Serbia. This variant could represent one of the
genetic factors that confer a predisposition to develop ALC.Book of abstracts: 2nd B&H Symposium of Laboratory Geneticists and Molecular Biologists (with International Participation) May, 202
Herbicide-treated soil as a reservoir of beneficial bacteria: microbiome analysis and PGP bioinoculants in maize
No full textHerbicides are integral to agricultural weed management but can adversely affect non-target organisms, soil health, and microbiome. We investigated the effects of herbicides on the total soil bacterial community composition using 16S rRNA gene amplicon community profiling. Further, we aimed to identify herbicide-tolerant bacteria with plant growth-promoting (PGP) capabilities as a mitigative strategy for these negative effects, thereby promoting sustainable agricultural practices