Determining the Cut-Off Value of Pro-Gastrin Releasing Peptide (ProGRP) in Lung Cancer According to Population Characteristics

The standardisation process consisted of determining tumour marker levels in all relevant population groups which are connected with the biology of the marker in normal and tumourous cells. This makes clinical application possible. ProGRP serum levels were measured in 273 healthy subjects, 176 patients with benign diseases and tumours, 200 with small cell lung cancer (SCLC), 294 with non-small cell lung cancer (NSCLC), 21 with carcinoid tumour, 93 with undifferentiated lung cancer, 35 with mixed SCLC-NSCLC, and 189 with other malignancies. ProGRP levels in patients with SCLC and SCLC-NSCLC were significantly higher than in all the other groups (p = 5.4 ´ 10–3). Moreover, in SCLC patients ProGRP levels significantly correlate with the extent of the disease and the patients’ smoking habit. The cut-off level of ProGRP for SCLC is 65.89 pg/mL in the Croatian population. It is based on 96.8% specificity in benign diseases which cause problems in differential diagnosis. The sensitivity of ProGRP was 85% at the time of SCLC diagnosis

ICTP in Bone Metastases of Lung Cancer

Bone metastases often appear in advanced stages of lung cancer. They are the result of modulation of bone metabolism by tumor cells that migrated into bone microenvironment and degraded bone organic matrix. Measurement of C-terminal telopeptide of type I collagen (ICTP) in the serum of subjects with lung cancer with and without bone metastases and healthy population is the way to explore bone resorption. In 343 subjects included in this research ICTP level was significantly higher in the bone metastasis than other two groups. The existence of pathologic fracture significantly increased ICTP level. ICTP showed sensitivity of 66.0% in bone metastases at 95.0% specificity in lung cancer stages IA and IB. ICTP is a good diagnostic marker in detection of bone metastasis of lung cancer. Its level can distinguish lung cancer with and without bone involvement and can be used as an addition to standard techniques used in diagnostics of bone metastasis

ICTP in Bone Metastases of Lung Cancer

Bone metastases often appear in advanced stages of lung cancer. They are the result of modulation of bone metabolism by tumor cells that migrated into bone microenvironment and degraded bone organic matrix. Measurement of C-terminal telopeptide of type I collagen (ICTP) in the serum of subjects with lung cancer with and without bone metastases and healthy population is the way to explore bone resorption. In 343 subjects included in this research ICTP level was significantly higher in the bone metastasis than other two groups. The existence of pathologic fracture significantly increased ICTP level. ICTP showed sensitivity of 66.0% in bone metastases at 95.0% specificity in lung cancer stages IA and IB. ICTP is a good diagnostic marker in detection of bone metastasis of lung cancer. Its level can distinguish lung cancer with and without bone involvement and can be used as an addition to standard techniques used in diagnostics of bone metastasis

HSA carbonylation with methylglyoxal and the binding/release of copper(II) ions

The potential of carbonylation with methylglyoxal to alter HSA's binding affinity for copper(II) ions and its influence on the release of copper(II) ions from copper-HSA complexes were studied. The affinity of HSA to coordinate copper(II) decreased upon carbonylation of the Cys34-SH group. Carbonylation of copper-HSA complexes caused a decrease in Cys34-SH content, conformational changes and the release of copper(II) ions. The ratio between the percentage of reduction in the Cys34-SH group content and the percentage of release of copper(II) from complexes is 2.12 +/- 0.28. Because the same ratio (1.96 +/- 0.36) was obtained upon oxidation of the Cys34-SH group (with no changes in HSA conformation), the binding/release of copper (II) by HSA depended mainly on the redox state of the Cys34-SH group. The contents of Cys34-SH and HSA-bound copper(II) ions in the diabetic group (0.457 +/- 0.081 mol SH per mol HSA, 10.7 +/- 0.01 mmol per mol HSA, resp.) were significantly lower (p lt 0.01) compared to the control group (0.609 +/- 0.027 mol SH per mol HSA; 13.4 +/- 0.01 mmol per mol HSA, resp.). Very strong correlations between the values for HSA-SH and glycated haemoglobin, HbA1c, (R = -0.803, p lt 0.01), and between the values for the HSA-bound copper(II) content and HSA-SH content (R = 0.841, p lt 0.002) were found in the diabetic group. Thus, HSA carbonylation leads to decrease in HSA-SH content and to the impairment of its copper(II) binding capacity that could contribute to further enhancement of oxidative and carbonyl stress in diabetes (as well as in other diseases with carbonyl stress)

Effect of enriched environment on serotonin and RNA editing of serotonin 2C receptor is specific for brain regions and mouse strains

Serotonin neurotransmission is sensitive to environmental stimuli. Serotonin receptor 2C (HTR2C) undergoes dynamic A-to-I editing that fine-tunes cell response to serotonin and is altered in depressed suicide victims and by pharmacological treatments. We aimed to explore a mediating role of Htr2c mRNA editing in response to enriched environment and factors involved in this response. Three-week-old BALB/c and C57BL/6 male mice were housed in enriched and standard conditions for four weeks. Htr2c mRNA editing pattern and expression, serotonin level and expression of Adar and Adarb1 mRNAs (coding enzymes catalyzing A-to-I editing) and Snord115 RNA (regulating Htr2c mRNA alternative splicing and editing) were measured in prefrontal cortex (PFC) and hippocampus (HC), brain regions implicated in suicidal behavior. BALB/c mice, a “stress-sensitive” strain due to genetically determined lower serotonin level, responded to enriched conditions by adapting the Htr2c editing pattern to a slight serotonin decrease in PFC and a significant increase in HC. C57BL/6 mice, a “stress-resilient” strain, responded to enriched environment by increasing the serotonin level and changing Adar and Adarb1 mRNAs expression in HC, and without changes in PFC. Our findings suggest that the enriched environment effect on the serotonin level and a mediating role of Htr2c mRNA editing in PFC depend on the genetic background and its interactions with the environment. On the other hand, changes in HC are primarily driven by enriched environment. Our results imply usefulness of enriched environment paradigm for understanding interactions of genetic and environmental factors underlying suicidal behavior, which might improve psychological treatments.BOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi

Srbija bez fosilnih goriva

Osmotreni porast srednje globalne temperature, koji sa sobom nosi i niz drugih dramatičnih promena unutar klimatskog sistema u direktnoj je vezi sa antropogenim emisijama gasova staklene bašte, na prvom mestu usled sagorevanja uglja, nafte i gasa. Ostanak i najmanjih pozitivnih neto emisija znači da problem nije rešen već samo da smo loš scenario odložili za dogledno vreme. Pariskim sporazumom je predviđeno dostizanje globalne neto nulte emisije GHG u drugoj polovini ovog veka. Ovaj zahtev se odnosi i na Republiku Srbiju koja je potpisala i ratifikovala Pariski sporazum. U članku je opisan predlog transformacije energetskog sektora Republike Srbije kako bi se omogućilo dostizanje nulte emisije iz energetskog sektora. Scenario opisuje uvođenje održive biomase i masivnu instalaciju solarnih i vetro elektrana do 2050. godine kojim bi se zamenio postojeći energetski sektor zasnovan na fosilnim gorivima. Razmatran je i finansijski aspekt ovakve tranzicije. Procenjena investicija u tranziciju na 100% obnovljive izvore energije jednaka je današnjim dodatnim zdravstvenim troškovima zbog zagađenja iz termoelektrana na ugalj. Pored unapređenja životne sredine, tranzicija bi omogućila nova radna mesta i unapređenja energetske bezbednosti naše zemlje

Between art and engineering: Studies on postwar architecture in Belgrade and Serbia

Publikacija nastaje kao prod višegodišnje saradnje sa gostujućim profesorom Lukom Skansijem u sklopu predmeta "Posebni problemi istraživanja arhitekture i urbanizma" na prvoj godini doktorskih studija. Tema trogodišnjeg ciklusa predavanja i diskusija, koje je vodio prof. Skansi između 2015 i 2017. godine, bio je pojam tektonike u arhitekturi, odnosno razvoj tog teoretskog i analitičnog pojma od sredine devetnaestog veka do danas. Studenti su bili pozvani da za svoj seminarski rad izvedu složenu i iscrpnu tektonsku analizu na jednoj relevantnoij arhitekturi izgrađenoj u Srbiji u konktekstu socijalističke Jugoslavije, u periodu između pedesetih i osamdesetih godina prošlog veka.urednik: Biljana JotićKategorija: M105 Učešće na 45. Salonu arhitekture, 28. mart - 29. april 2023. godine. u Muzeju primenjene umetnosti, Beograd, u kategoriji: Arhitektonska kritika i publikacij

Neurofilament as a biomarker of response to genetically designed therapies for spinal muscular atrophy

Considering the substantial impact of genetic therapies for spinal muscular atrophy (SMA), longitudinal follow-up of patients undergoing treatment is crucial to effectively monitor treatment response. While functional rating scales are commonly used as primary outcome measures, they may not fully capture all the therapeutic benefits. To address this limitation, the phosphorylated neurofilament heavy chain (pNFH) protein has emerged as a promising biomarker for evaluating treatment response. pNF-H is a neuron- specific filament that exhibits increased levels in the cerebrospinal fluid (CSF) and plasma in the presence of neuronal degeneration. Our study includes individuals treated with Nusinersen (CSF and plasma samples) and Risdiplam (plasma), as well as age- and sex-matched control subjects (CSF and plasma). By examining the dynamics of pNF-H levels in these groups, we sought to identify significant differences indicative of treatment response. Before treatment, SMA individuals typically exhibit higher levels of pNF-H compared to non-SMA individuals. Elevated levels of pNF-H are associated with more severe clinical manifestations of the disease. During Nusinersen treatment, a notable decline in pNF-H levels during the first 2 months can be observed. Current findings suggest that genetic therapies have a notable impact on reducing pNF-H levels over time. By examining the changes in pNF-H levels, our study offers valuable insights into the underlying biochemical alterations associated with these therapies. Furthermore, it supports the use of pNF-H as a complementary measure to functional rating scales and as a potential biomarker for evaluating treatment effectiveness and monitoring disease progression in SMA

Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia

IntroductionBiomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise.MethodsWe conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3).ResultsSMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment.ConclusionOur findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration