imagine (Institute of molecular genetics and genetic engineering)
Not a member yet
3088 research outputs found
Sort by
Micro-wave induced pyrolysis of low density polyethylene (LDPE) and biodegradation of resulting wax in soil and by defined microbial consortia is closing the loop towards LDPE upcycling
No full textPlastic has become essential in daily life, replacing traditional materials like glass and wood due to its flexibility, durability, strength, and cost-effectiveness. However, the global plastic production surged to nearly 400 million tons in 2020, causing significant environmental accumulation. Polyethylene (PE), a ubiquitous polymer, poses recycling challenges due to its stability and widespread use in layered products, contributing to long-term pollution. This study focuses on PE degradation challenges, advocating for integrated chemical and biological treatments. Chemical methods like pyrolysis show promise but aren't fully eco-friendly. Microwave-induced pyrolysis emerges as a viable alternative, offering faster, targeted heating with lower energy consumption. Using microwave-absorbent materials such as silicon carbide, this method efficiently breaks down even challenging low-density PE (LDPE), yielding wax products of 68–91 % yield, with reduced molecular weight suitable for further biological degradation. Biodegradation experiments demonstrated over 95 % degradation by defined microbial consortia and considerable degradation in soil without bioaugmentation. The Rhodococcus consortium showed exceptional potential, degrading 90 % of LDPE-wax as a carbon source within 28 days, particularly strain CHBE-144 achieving 98 % degradation in just 14 days. Genomic analysis revealed enzymes crucial for alkane and plastic breakdown, with strains capable of producing biosurfactants, suggesting up-cycling potential for PE-derived materials into value-added products. Integrating microwave-induced pyrolysis with microbial biodegradation offers a promising pathway for managing PE waste sustainably, potentially reducing environmental impact while creating valuable resources from plastic waste. Further research is warranted to optimize these processes and scale them for practical application in waste management and resource recovery efforts globally
The role of ankrd1a in zebrafish skeletal muscle repair
No full textAnkyrin repeat domain 1 (ANKRD1/CARP) is involved in muscle cell
stress response. Through interaction with the N2A region of titin and
mediation in titin binding to actin filaments, ANKRD1 protects muscle
cells from being overstretched. In the nucleus, it plays the role of
transcriptional cofactor. ANKRD1 is upregulated in muscle diseases,
including muscular dystrophy and spinal muscular atrophy. Our
investigation of zebrafish homolog, ankrd1a showed its activation
during the repair of skeletal muscle and regeneration of the heart,
suggesting conserved function in muscle cell stress response
Molecular characterization of ANKRD1 in rhabdomyosarcoma cell lines: expression, localization, and proteasomal degradation
No full textRhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. Respecting the age of the patients and the tumor aggressiveness, investigation of the molecular mechanisms of RMS tumorigenesis is directed toward the identification of novel therapeutic targets. To contribute to a better understanding of the molecular pathology of RMS, we investigated ankyrin repeat domain 1 (ANKRD1), designated as a potential marker for differential diagnostics. In this study, we used three RMS cell lines (SJRH30, RD, and HS-729) to assess its expression profile, intracellular localization, and turnover. They express wild-type ANKRD1, as judged by the sequencing of the open reading frame. Each cell line expressed a different amount of ANKRD1 protein, although the transcript level was similar. According to western blot analysis, ANKRD1 protein was expressed at detectable levels in the SJRH30 and RD cells (SJRH30 > RD), but not in the HS-729, even after immunoprecipitation. Immunocytochemistry revealed nuclear and cytoplasmic localization of ANKRD1 in all examined cell lines. Moreover, the punctate pattern of ANKRD1 staining in the nuclei of RD and HS-729 cells overlapped with coilin, indicating its association with Cajal bodies. We have shown that RMS cells are not able to overexpress ANKRD1 protein, which can be attributed to its proteasomal degradation. The unsuccessful attempt to overexpress ANKRD1 in RMS cells indicates the possibility that its overexpression may have detrimental effects for RMS cells and opens a window for further research into its role in RMS pathogenesis and for potential therapeutic targeting
HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING
Get PDFSkin microbiome emerged as an important
factor which can balance tissue repair process
and wound healing. Recent evidence suggest
that intracellular bacterial localization could be
associated with the aberrant healing observed
in patients with chronic wounds, while therapeutics
targeting intracellular bacteria remain
limited. Probiotic lactobacilli and their bioactive
lysates (postbiotics) are well known for their role
in maintenance of gut epithelial homeostasis.
Hence, in this study we focused to understand
the mechanisms of cutaneous response to fourteen
postbiotics derived from different lactobacilli
to reduce intracellular Staphylococcus aureus
colonization and promote healing. Latilactobacillus
curvatus BGMK2-41 demonstrated the
most efficient capability to reduce intracellular infection by S. aureus in keratinocytes in vitro and
infection of human skin explants. Reduction of
bacterial number was followed by upregulation
of the expression of antimicrobial response
genes. Furthermore, BGMK2-41 postbiotic treatment
stimulates keratinocyte migration in vitro
and increases expression of anti-inflammatory
cytokine IL-10, promotes wound closure and
strengthens the epidermal barrier via upregulation
of tight junction proteins in a human ex vivo
wound model. Altogether, this study provided
evidence that postbiotics could stimulate fortification
of epithelial barrier to suppress dissemination
of intracellular pathogens which can be
used as a novel approach to treat dermatologic
and wound healing disorders associated with
persistent infections.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi
EMPOWERING ANTIFUNGAL DRUGS DISCOVERY THROUGH THE ZEBRAFISH-INFECTIOUS DISEASES MODELLING
Get PDFFungal infections, once considered a rare disease,
have become an everyday problem in modern
societies, posing major challenges to global
health. It is estimated that more than one billion
people are affected by fungal infections and 1.6
million people succumb to these diseases every
year. Of the 600 species of fungi capable of causing
infections in humans, species of the genus
Candida cause more than 85% of infections, especially
C. albicans, which has become a serious
threat to human health in immunocompromised
and immunosuppressed individuals. Unfortunately,
the current arsenal of clinical drugs relies
on only four classes of approved drugs (polyenes,
azoles, echinocandins and allylamines), which
are only partially effective, resulting in incomplete
eradication of the fungal infection. In
addition, the serious side effects, ranging from
systemic or organ-specific toxicity to poor bioavailability
and low activity, significantly hamper
the clinical use of antifungals. These problems
call for new effective and safe antifungal agents,but also for appropriate preclinical models to accurately
study potential adverse effects on the
human population and test their efficacy against
fungal infections. In this sense, zebrafish (Danio
rerio) embryos have become one of the most
powerful preclinical animal models in infection
biology and drug discovery, offering the unique
opportunity to simultaneously monitor the safety
and efficacy of the applied molecule in real
time. With the aim of providing a preclinical platform
for the identification of new safe antifungal
drugs to effectively control C. albicans infection,
we comprehensively tested the toxicity of 13
clinical antifungal drugs in the zebrafish embryo
model. The 21 toxicity endpoints, including
survival, teratogenicity, cardiotoxicity and hepatotoxicity,
were evaluated and compared with
adverse effects described in rats and humans. Of
the clinical drugs, the efficacy of fluconazole and
voriconazole was evaluated in the zebrafish - C.
albicans model of systemic and wound biofilm
infection.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi
Characterization of the ANKRD1 gene and the effect of violacein on rhabdomyosarcoma cells in vitro
No full textRabdomiosarkomi (RMS) su najčešći maligni tumori mekog tkiva kod dece i adolescenata. Zbog
uzrasta pacijenata i agresivnosti tumora, lečenje predstavlja veliki izazov. Da bi sе doprinelо
identifikaciji novih terapeutskih targeta i terapeutika za RMS, u ovoj disertaciji je istražen
ANKRD1 (eng. ankyrin repeat domain 1), označen kao potencijalni marker za diferencijalnu
dijagnostiku, i antitumorski potencijal prirodnog pigmenta violaceina, koristeći tri ćelijske
linije RMS.
Svaka linija je eksprimirala različite količine ANKRD1 proteina, iako je nivo transkripta bio
sličan. Imunocitohemijom je otkrivena jedarna i citoplazmatska lokalizacija ANKRD1 u svim
linijama. Tačkasti obrazac bojenja ANKRD1 u jedrima RD i HS-729 ćelija poklapao se sa
markerom Kahalovih tela. Povećanje ekspresije ANKRD1 nije bilo moguće, verovatno usled
proteazomalne degradacije. Ovo ukazuje na štetne efekte povećanja ekspresije ANKRD1 na
ćelije RMS, sugerišući opravdanost daljih istraživanja njegove uloge u patogenezi RMS i
razmatranja kao terapetskog targeta.
Violacein je pokazao citotoksični efekat na ćelije RMS, indukujući apoptozu, dok nije imao
značajan uticaj na preživljavanje neizmenjenih ćelija i embriona zebrica pri koncentracijama
toksičnim za tumorske ćelije. Uticao je i na migratorni potencijal ćelija RMS. Tokom tretmana
se zadržavao na površini ćelija, a njegovo dejstvo nije zavisilo od oksidativnog stresa.
Dodavanje violaceina je povećalo toksičnost doksorubicina prema ćelijama RMS.
Ovo istraživanje doprinosi boljem razumevanju funkcije ANKRD1 u RMS i ukazuje na potencijal
violaceina kao dodatne terapijske opcije za lečenje ovog tipa tumora.Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and
adolescents. Due to the age of patients and the tumor aggressiveness, treatment presents a
significant challenge. To contribute to the identification of new therapeutic targets and
treatment options for RMS, we investigated ANKRD1 (ankyrin repeat domain 1), marked as a
potential differential diagnostic marker, and the antitumor potential of natural pigment
violacein, using three RMS cell lines.
Each line expressed a different amount of ANKRD1 protein, although the transcript levels were
similar. Immunocytochemistry revealed nuclear and cytoplasmic localization of ANKRD1 in all
examined lines. The punctate pattern of ANKRD1 staining in the nuclei of RD and HS-729 cells
overlapped with the marker of Cajal bodies. Overexpression of ANKRD1 was not achieved in
the cells, likely due to proteasomal degradation. The unsuccessful overexpression of ANKRD1
indicates its detrimental effects on RMS cells, suggesting the need to investigate its role in RMS
pathogenesis and potential as a therapeutic target.
Violacein demonstrated a cytotoxic effect on RMS cells, inducing apoptosis, while it did not
significantly affect the survival of non-malignant cells and zebrafish embryos at concentrations
toxic to tumor cells. Violacein also affected the migratory potential of RMS cells. It did not
penetrate the cells but remained on their surface, and its action was independent of oxidative
stress. The addition of violacein increased the toxicity of doxorubicin to RMS cells.
This study contributes to a better understanding of the ANKRD1 function in RMS and highlights
the potential of violacein as an additional therapeutic agent for this tumor
Modifikacija mikrobiote kao pristup lečenju multiple skleroze
No full textThe advancement in new-generation sequencing and
big-data analysis has contributed greatly to ourunderstanding of the crucial role of gut microbiota in
both healthy organism development and various
pathological conditions. Bacterial strains residing in
the anaerobic environment of the colon, particularly
those capable of producing short-chain fatty acids
(SCFAs), play a significant role in maintaining gut
homeostasis and consequently, the overall well-being
of the host. Notably, a decrease in butyric acid (BA)-
producing bacteria has been linked to lower BA levels
observed in patients with multiple sclerosis (MS).
Moreover, the immunoregulatory properties of BA
have been demonstrated on various immune cells of
lymphoid and myeloid origin in vitro. Hence, the
study aimed to use different media in anaerobic con-
ditions to isolate bacterial strains with high BA pro-
duction capacity from the feces of healthy donors,
and to assess the effects of isolates in Caco-2/periph-
eral blood mononuclear cells (PBMC) in vitro model
of gut inflammation, Caenorhabditis elegans model
for neurodegenerative studies, and in mice model of
MS. Considering the sensitivity of these bacteria to
oxygen, the cultures with metabolites produced by
these bacteria during the night (postbiotic), were
used in experiments. Based on the high BA produc-
tion (15 mM), the anti-inflammatory effects in Caco-
2/PBMC co-culture, and neuromodulatory effects in
C.elegans model, Faecalimonas sp. NGB245 was
selected for further assessment in the mice model of
MS. Myelin oligodendrocyte glycoprotein peptide/
complete Freund’s adjuvant/pertussis toxin-induced
experimental autoimmune encephalomyelitis (EAE)
in C57BL6 mice was used as a model of MS. The
EAE mice consumed NGB245-postbiotic over 15
days in a 16-hour/day regime, ad libitum. The con-
trol group of EAE mice received supplementation
with PYG medium enriched with cellobiose and
starch, which was used for NGB245 cultivation, in
the same regime. The supplementation with
NGB245-postbiotic resulted in alleviation of daily
clinical scores, maximal clinical scores, and duration
of EAE compared to the control group. These effects
on EAE symptoms were accompanied by a decrease
in the abundance of Th1 and Th17 cells, as well as
different proinflammatory myeloid cells, along with
an increase in the level of myeloid-derived suppressor
cells in the central nervous system of NGB245-post-
biotic-supplemented EAE mice. This was associated
with a higher diversity of microbiota in the colon.
These findings underscore the potential of using the
postbiotics of BA-producing anaerobic bacteria to
preserve immune-microbiota homeostasis and miti-
gate the development of autoimmune processes.Napredak u metodama sekvenciranja nove generacije i analizi velikih podataka u velikoj meri je doprineo na{em razumevanju ključne uloge crevne mikrobiote
kako u razvoju zdravog organizma, tako i u raznim
patolo{kim stanjima. Sojevi bakterija koji `ive u
anaerobnom okru`enju debelog creva, posebno oni
koji su sposobni da proizvode masne kiseline kratkog
lanca (SCFA), igraju zna~ajnu ulogu u odr`avanju
homeostaze barijere i imunskog sitema creva.
Smanjenje bakterija koje proizvode SCFA je povezano
sa ni`im nivoima ovih kiselina kod pacijenata sa mul-
tiplom sklerozom (MS). Tako|e je pokazano da ove
kiseline imaju izra`ene imunomodulatorne efekte na
razli~ite populacije limfocita i }elija mijeloidnog
porekla. Stoga je cilj na{e studije bio da se iz fecesa
zdravih davalaca, kori{}enjem razli~itih medijuma u
anaerobnim uslovima, izoluju bakterijski sojevi sa
visokim kapacitetom za proizvodnju SCFA. U nas-
tavku je analiziran efekat ovih izolata u kulturama
intestinalnih epitelnih }elija Caco-2 i mononuklearnih
}elija periferne krvi (PBMC) u in vitro modelu zapa -
ljenja creva, u modelu Caenorhabditis elegans za
ispitivanja neuromodulatornih efekata, i na mi{ijem
modelu MS-a. Obzirom na osetljivost ovih bakterija
na kiseonik, u eksperimentima su kori{}ene kulture
sa metabolitima koje su bakterije proizvele tokom
no}i (postbiotici). Na osnovu visoke proizvodnje BA
(15 mM), anti-inflamatornog efekta u Caco-2/PBMC
kokulturi i neuromodulatornih efekata u modelu C.
elegans, Faecalimonas sp. NGB245 je odabran za
dalju procenu efekta u mi{ijem modelu MS-a. Kao
model MS-a kori{}eni su C57BL6 mi{evi kojima je
indukovan eksperimentalni autoimunski encefalomi-
jelitis (EAE) aplikacijom peptida mijelinskog oligo-
dendrocitnog glikoproteina, kompletnog Frojndovg
adjuvansa i toksina pertusisa. EAE mi{evi su pili
NGB245-postbiotik tokom 15 dana u re`imu od 16
sati dnevno, ad libitum. Kontrolna grupa EAE mi{eva
je pila PYG medijumom oboga}en celobiozom i
skrobom, koji je kori{}en za kultivaciju NGB245, u
istom re`imu. Primena NGB245-postbiotika je kod
EAE-mi{eva dovela do razvijanja bla`ih dnevnih
klini~kih rezultata, maksimalnih klini~kih rezultata i
kra}eg trajanja EAE u pore|enju sa kontrolnom
grupom. Ovi efekti NGB245-postbiotika na simp-
tome EAE bili su pra}eni ni`om u~estalo{}u Th1 i
Th17 }elija, kao i razli~itih proinflamatornih mijeloid-
nih }elija, zajedno sa pove}anjem nivoa supresorskih
}elija mijeloidnog porekla u centralnom nervnom sis-
temu. Mikrobiota u debelom crevu `ivotinja koje su
pile postbiotik imala je ve}i diverzitet od kontrolne
grupe `ivotinja. Rezultati ove studije ukazuju na
potencijal terapijskih pristupa baziranih na primeni
postbiotika anaerobnih bakterija koje produkuju buti-
rat kako bi se o~uvala homeostaza mikrobiote i
ubla`io razvoj autoimunskih procesa.Book of abstract: XIII International Serbian Congress of Medical Biochemistry and Laboratory Medicine. 16-18 September 2024, Belgrade, Serbia
Antidepresivni potencijal postbiotika u animalnom modelu depresije
No full textDepression is the most common psychiatric disorder
that affects more than 264 million people worldwide.
Antidepressants struggle with great challenges such as high rate of relapse, delayed clinical response and
numerous side-effects. Postbiotics, bioactive com-
pounds produced by psychobiotics, the emerging
group of probiotics that have beneficial effects on
mental health, have already shown promising results
in mood disorder alleviation. This study aimed to
evaluate the antidepressant potential of postbiotic
Phocaeicola vulgatus NGB218. P. vulgatus NGB218,
isolated from the fecal samples of a healthy donor,
was cultivated in PYG medium within an anaerobic
chamber. Among 35 isolated strains, P. vulgatus
NGB218 was selected for its pronounced production
of GABA and its observed anti-inflammatory effects
in Caco2 cell cultures, as well as its neural impact on
the Caenorhabditis elegans model. We used rats
exposed to chronic unpredictable mild stress (CUMS)
as an animal model of depression. Three-weeks old
rats were divided in 3 groups (n=16): control, non-
treated rats; rats treated with Pyg medium and rats
treated with P. vulgatus NGB218 postbiotic for 8
weeks. After 4 weeks half of the animals from each
group (n=8) was subjected to CUMS for 4 weeks.
Anhedonia, a core symptom of depression, was mon-
itored using sucrose preference and splash test, while
marble burying test and elevated plus maze were
used to score anxiety. The levels of corticosterone
and pro-inflammatory cytokines TNF-a, IL-1 and IL-
6 in serum were measured using ELISA kits.
Treatment with postbiotic P. vulgatus NGB218
demonstrated both antidepressive and anxiolytic
effects in CUMS rats.Depresija je naj~e{}e psihijatrijsko oboljenje od kog
boluje vi{e od 264 miliona ljudi {irom sveta.
Upotreba antidepresiva se suo~ava sa velikim izazovima poput visoke stope relapsa, odlo`enog klini~kog
odgovora i brojnih ne`eljenih efekata. Postbiotici,
bioaktivne komponente produkovane od strane psi-
hobiotika, probiotika koji imaju blagotvorni efekat na
mentalno zdravlje, pokazali su obe}avaju}e rezultate
u ubla`avanju poreme}aja raspolo`enja. Ova studija
ima za cilj da proceni antidepresivni potencijal post-
biotika Phocaeicola vulgatus NGB218. P. vulgatus
NGB218 je izolovan iz fecesa zdravog donora i kul-
tivisan u Pyg medijumu u anaerobnoj komori. P.
vulga tus NGB218 je odabran me|u 35 izolovanih
sojeva na osnovu najve}e produkcije GABA, anti-
infla ma tornog efekta uo~enog na Caco2 }elijama,
kao i zbog uticaja na nervni sistem koji je zabele`en
u eksperimentima na modelu Caenorhabditis ele-
gans. Pacovi podvrgavani hroni~nom nepredvidivom
blagom stresu su kori{}eni kao `ivotinjski model
depresije. Pacovi stari tri nedelje su podeljeni na tri
grupe (n=16): (1) kontrolni, netretirani pacovi; (2)
pacovi tretirani Pyg medijumom i (3) pacovi tretirani
P. vulgatus NGB218 postbiotikom u trajanju od 8
nedelja. Posle 4 nedelje tretmana, polovina pacova iz
svake grupe (n=8) je podvrgnuta CUMS-u naredne
4 nedelje. Test zainteresovanosti za zasla|en rastvor i
test prskanja (engl.splash test) kori{}eni su za mere -
nje anhedonije, glavnog simptoma depresije, a test
zakopavanja klikera i izdignutog lavirinta za procenu
anksioznosti. Koncentracija kortikosterona i proinfla -
matornih citokina TNF-a, IL-1 i IL-6 u serumu paco-
va merena je odgovaraju}im ELISA kitovima.
Tretman postbiotikom P. vulgatus NGB218 pokazao
je antidepresivno i anksioliti~ko dejstvo u CUMS
`ivotinjskom modelu depresije.Book of abstract: XIII International Serbian Congress of Medical Biochemistry and Laboratory Medicine. 16-18 September 2024, Belgrade, Serbi
(PB3047) REAL-WORLD 7-YEAR SINGLE-CENTER EXPERIENCE IN THE MANAGEMENT OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
No full textBackground:
Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma, with the vast
majority of cases being diffuse large B cell lymphoma (DLBCL) by histopathology. The nature of the
disease and its localization consequently determines clinical presentation, which leads to reduced
mobility and poor general condition in many patients (pts) diagnosed with PCNSL. These pts are
underrepresented in clinical trials, which may distort the impression of the prognosis of PCNSL pts in
general.
Aims:
To present a real-world cohort of unselected PCNSL pts and their clinical and laboratory features,
treatment and outcome.
Methods:
We conducted a single-center retrospective study presenting real-world data on PCNSL in the Clinic of
Hematology, University Clinical Center of Serbia. Data from 26 pts diagnosed and treated from 2017 to
2023 were collected from medical records and analyzed by basic statistical methods.
Histology other than DLBCL was excluded from the study.
Results:
Two-thirds of pts were males (65%, 17pts). The median age at diagnosis was 61 years. 85% of pts
presented with focal neurological deficit, 58% with signs of increased intracranial pressure, 31%
with behavioral disorder, and 27% with seizures and ocular symptoms. Focal disease was present in
19 pts (73%), while 18 pts (69%) had deep brain structures involved. Memorial Sloan Kettering
Cancer Center (MSKCC) score was 1 in 2 pts (8%), 2 in 7 pts (27%), and 3 in 17 pts (65%). Two-thirds
(17 pts, 65%) presented with poor performance status (ECOG 3-4 or Karnofsky index ≤50%). Most
pts (22/24, 81%) exhibited a non-GCB immunohistochemistry pattern. In 3/25 pts (11%) venous
thromboembolic event (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) was
confirmed.
The diagnosis was made after total tumor extirpation or maximal resection in 12 pts (46%). Almost all
pts (24/26, 92%) were treated with high-dose methotrexate (HDMTX) based therapy, 20 pts (77%)
with the addition of rituximab, while 2 pts (8%) received only corticosteroids. The induction phase
was completed in 14 pts (58%). Overall response rate (ORR) after induction was 62.5% (complete
response [CR] in 29.2% and partial response [PR] in 33,3% of 24 pts with known response data).
Median progression-free survival (PFS) was 7.5 months (m) (range, 0-71), and median overall
survival (OS) was 10 m (range, 2-72). Only 9 pts (35%) were alive at the last follow-up.
PFS was significantly prolonged in pts without VTE (P=0.047), pts who experienced diagnostic total or
maximal tumor resection (P=0.008), those treated with addition of rituximab (P<0.001), pts who
EHA2024 | Abstract Submission
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), addition of rituximab to HDMTX-based induction
treatment (P<0.001), response to induction treatment (P<0,001), consolidative RT or ASCT (P<0.001)
showed statistically significant positive impact on OS.
Summary/Conclusion:
A significant number of patients in real-world settings present with poor performance status and are
ineligible for intensive treatment, leading to poor outcomes in general. In our cohort, survival was
significantly affected by VTE, total/maximal tumor resection, addition of rituximab, achievement of
CR/PR to induction treatment, and consolidation. Larger real-world databases are warranted for more
reliable conclusions.29th Congress of the European Hematology Association EHA2024 Annual Congress Edition June 202
Frequency of genetic variants associated with celiac disease and lactose intolerance and changes in intestinal microbiota in children with neurodevelopmental disorders
No full textNeurorazvojni poremećaji (NRP) su poremećaji koji se javljaju rano u detinjstvu i karakteriše ih kašnjenje
u više sfera razvoja. Najteža forma ovih poremećaja je autizam. Smatra se da značajnu ulogu u etiologiji NRP
imaju genetički i sredinski faktori, kao i njihova interakcija. U poslednje vreme posebna pažnja posvećuje
se komorbidnim stanjima, naročito gastrointestinalnim smetnjama. Prema Opioidnoj teoriji, opioidni
peptidi poreklom od proteina kazeina i glutena, usled povećane propustljivosti crevnog epitela ulaze u
cirkulaciju i prolazeći kroz krvnomoždanu barijeru reaguju sa opioidnim receptorima u centralnom
nervnom sistemu, dovodeći do nastanka nekih neuroloških i psihijatrijskih simptoma. Stoga su istraživanja
usmerena ka boljem razumevanju potencijalnih mehanizama nastanka povećane propustljivosti crevnog
epitala kod dece sa NRP, odnosno da li do nje dolazi zbog genetski predisponirane intolerancije na neku
komponentu hrane ili usled crevne disbioze.Neurodevelopmental disorders (NDDs) are disorders that appear early in childhood and are characterized
by delays in several spheres of development. The most severe form of these disorders is autism. Genetic
and environmental factors, and their interaction, are considered to play a significant role in the etiology of
NDD. Recently, special attention was directed towards comorbid conditions, especially gastrointestinal
disorders. According to the Opioid theory, opioid peptides originating from casein and gluten proteins, due
to the increased permeability of the intestinal epithelium, enter the circulation and, passing through the
blood-brain barrier, react with opioid receptors in the central nervous system, leading to the appearance of
some neurological and psychiatric symptoms. Therefore, the research is focused on better understanding
of potential mechanisms of increased permeability of the intestinal epithelium in children with NDD, i.e.
whether it occurs due to genetically predisposed intolerance to some food component or due to intestinal
dysbiosis