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The evolving therapeutic landscape of spinal muscular atrophy – A scoping review of investigational agents, emerging delivery technologies and strategic innovations
No full textSpinal muscular atrophy (SMA) is a severe neuromuscular disease with emerging therapeutic complexity. This review aims to systematically map the global pipeline of investigational treatments for SMA. Using ClinicalTrials.gov and complementary international registries, we identified 21 planned or ongoing interventional trials from 2020 to 2025 targeting novel agents, alternative dosing and delivery routes. Inclusion criteria focused on unapproved therapies or new uses of existing drugs, with rigorous data extraction across demographics, modalities and trial phases. Results reveal a shift towards dual-pronged strategies: refining SMN-targeted interventions and expanding SMN-independent approaches, such as myostatin inhibitors, neuromuscular modulators and ion-channel blockers. Early-phase outcomes suggest promising motor function improvements and acceptable safety profiles, though long-term efficacy remains under investigation. This evolving landscape underscores the importance of registry-based analyses in tracking translational innovation, informing stakeholders and guiding future research priorities
Exposure Assessment of Tropane Alkaloids via Barley Grain-Based Products Among Serbian Population
No full textDietary exposure to tropane alkaloids (TAs) in Serbia remains insufficiently investigated, while awareness among consumers and agricultural producers of potential exposure and related health risks, particularly for children, is low. Barley, a cereal widely used in food production, is still not included in the EU and Serbian regulations on maximum allowable atropine and scopolamine concentrations in food. However, the CONTAM panel established the group ARfD of 0.016 µg/kg bw/day for the sum of atropine and scopolamine. Therefore, a study was conducted on barley samples from organic and conventional production systems, in order to quantify the presence of atropine and scopolamine by LC-MS/MS. In all of the tested samples, both TAs were detected at concentrations above the LOD. The most contaminated sample was from the organic production, with the sum of atropine and scopolamine being 3.2 µg/kg. In order to evaluate the consumer risk from At and Sc in barley-based products, the EFSA framework for acute dietary exposure assessment was applied. The exposure was assessed for seven population groups consuming barley-based foods and beverages: toddlers, children, adolescents, adults, elderly, vegetarians, and pregnant women. The estimated daily intake, calculated according to the three consumption scenarios, did not exceed the established ARfD value. Since barley is not the only source of TA intake in Serbia, a prospective study on TA exposure should be performed in order to monitor TA concentrations, estimate exposure, and manage the risk
The influence of sociodemographic factors on blood lead levels in healthy adults living in Belgrade, Serbia
No full textLead is a highly recognised toxic metal. Long-term exposure to low Pb levels in the environment could induce adverse effects (developmental, neurological, cardiovascular, endocrine). Some developing countries, such as Serbia, has not identify the possible sociodemographic factors that could increase blood lead levels (BLL), yet. The aim of this study was to examine the effects of sociodemographic factors (gender, age, origin, smoking, sport activity, education, economy status, high traffic vicinity to the residence, and drinking habits) on BLL of voluntary blood donors, living in Belgrade, Serbia. The study included 984 participants. Blood samples were analysed using ICP-MS. The log-transformed BLL had a normal distribution. Geometric mean (18.6 µg/L, 95 %CI 17.8–19.4 µg/L) was similar with values obtained in some EU countries. However, 15.9 % of all participants had BLL levels higher than US CDC recommended threshold for BLL for adults (35 µg/L). Gender, age, smoking, and alcohol consumption were the significant factors that contributed almost 15 % to the BLL. Groups with the highest BLL were men, the eldest, active smokers, and the frequently alcohol drinkers. Education and economy status were observed as moderate to significant indirect factors via smoking, sport and residential environment. This study offers the first observation on the influence of a combination of socioeconomic and demographic factors on BLL in adults living in urban areas of Serbia, confirms and complements previous findings worldwide, and expands the knowledge on BLL in developing countries. Understanding the impact of various sociodemographic factors is necessary to reduce lead exposure of general population
Identification of Drug Repurposing Opportunities of Immunomodulatory Drugs for Inflammatory Bowel Disease Through Inverse Pharmacovigilance Signal Detection in the FAERS Database
No full textBackground/Objectives: Drug repurposing represents a promising strategy to expand ther-
apeutic options for inflammatory bowel disease (IBD), a chronic condition with persistent
unmet clinical needs. This study aimed to identify existing drugs with potential relevance
for IBD by exploring inverse associations in the FDA Adverse Event Reporting System
(FAERS) as a hypothesis-generating, real-world data approach. Methods: In this retrospec-
tive observational pharmacovigilance study, drug–IBD associations were extracted from
the FAERS database using OpenVigil 2.1. Inverse associations were identified based on
reporting odds ratios (ROR) < 1 with adjusted p-values < 0.05. Identified drug–event pairs
were further evaluated for pharmacokinetic feasibility, clinical applicability, and biological
plausibility in the context of IBD, with the exclusion of drugs with implausible indica-
tions, contraindications, or mechanisms inconsistent with IBD pathophysiology. Given
the immune-mediated nature of IBD and the breadth of the identified candidates, detailed
evaluation focused on immunomodulatory agents. Results: Among the 3585 initial drug–
IBD combinations, 73 candidates met the predefined criteria for statistical significance and
feasibility. From these, nine drugs were prioritized based on inverse signal strength and
mechanistic relevance to immune modulation pathways implicated in IBD. The strongest in-
verse association with IBD was observed for lenalidomide (ROR 0.056, 95% CI 0.043–0.073),
followed by dupilumab (ROR 0.213, 95% CI 0.185–0.245), cyclophosphamide (ROR 0.215,
95% CI 0.175–0.265), fingolimod (ROR 0.216, 95% CI 0.205–0.334), dimethyl fumarate (ROR
0.332, 95% CI 0.275–0.400), apremilast (ROR 0.357, 95% CI 0.296–0.431), imatinib (ROR
0.423, 95% CI 0.339–0.527), glatiramer acetate (ROR 0.446, 95% CI 0.352–0.565), and inter-
feron beta-1a (ROR 0.594, 95% CI 0.533–0.662). These agents possess immunomodulatory
properties relevant to inflammatory pathways implicated in IBD; however, clinical evidence
supporting the therapeutic efficacy of some candidates remains variable or incomplete.
Conclusions: By integrating inverse signal detection with clinical and biological assessment,
this study demonstrates how pharmacovigilance data can be extended from traditional
safety surveillance toward systematic drug repurposing applications. The findings generate
testable hypotheses and highlight candidate therapies that warrant further experimental
and clinical investigation in IBD
Ultrasound-Assisted Extraction of Bioactive Compounds from Strawberry Pomace: Optimization and Bioactivity Assessment
No full textThe growing production of strawberry-based foods generates large quantities of pomace, a phenolic-rich by-product with high valorization potential. This study aimed to optimize ultrasound-assisted extraction (UAE) of strawberry pomace and to evaluate the bioactivity of the resulting extracts. The greenness assessment using the AGREEprep metric yielded a score of 0.68/1, confirming the environmental friendliness of the process. Under the optimized UAE conditions (20 min, 50 °C, solid-to-liquid ratio 1:20 g/mL), the extract exhibited the highest total phenolic (16.49 mg GAE/g) and flavonoid contents (2.10 mg RE/g). The optimized extract showed strong antioxidant activity, with DPPH, ABTS, CUPRAC, and FRAP values of 32.70, 46.76, 57.29, and 38.90 mg TE/g, respectively. Enzyme inhibition was particularly pronounced against tyrosinase (55.45 mg KAE/g), while moderate inhibition of acetylcholinesterase and butyrylcholinesterase was also observed. Artificial neural network (ANN) modeling demonstrated excellent predictive performance (R2 > 0.99) and enabled effective optimization of extraction parameters. These findings confirm UAE as an efficient and sustainable approach for strawberry pomace valorization and highlight ANN-based optimization as a robust tool for developing multifunctional bioactive extracts for food, nutraceutical, and pharmaceutical applications
Does the carrier type affect the CQAs of liquisolid tablets with atorvastatin calcium?
No full textLiquisolid technique is a simple and cost-effective method to enhance the dissolution of
poorly soluble drugs. Porous carriers are crucial in these formulations, as their
physicochemical properties and compaction behaviour determine the amount of liquid phase,
and therefore drug, that can be incorporated, as well as the overall processability and
characteristics of liquisolid systems. In this study, liquisolid tablets were prepared using three
different porous carriers (Neusilin®US2, Syloid®XDP3050, and Fujicalin®) to investigate the
effect of carrier type on compaction behaviour and dissolution. Compaction properties
(tensile strength, work of compression, elastic recovery, and detachment and ejection
stresses) were measured, alongside contact angle and dissolution testing. All three carriers
produced tablets with acceptable mechanical strength (>1.7MPa) and moderate elastic
recovery (21–31%). Tablets with Syloid® required the highest net work of compression,
reflecting carrier’s rigid, brittle structure. Tablets with Fujicalin® showed the highest ejection
stress, likely due to lower liquid-loading capacity. In contrast, the formulation with Neusilin®,
which had the highest liquid load, demonstrated the lowest detachment and ejection stresses,
and the lowest net work of compression and elastic recovery, indicating efficient plastic
deformation and effective liquid distribution. Dissolution testing showed that formulations
with Neusilin® and Syloid® achieved rapid and complete drug release, with Syloid® being faster
(80% in 5 min), consistent with its high wettability (contact angle 17°). In comparison, tablets
with Fujicalin® released the drug more slowly and incompletely, likely due to poor wettability
(contact angle 52°) and fragmentation as dominant compression mechanism leading to higher
tensile strength. These results demonstrate that choice of porous carrier strongly affects
compaction behaviour, which, together with wettability, governs drug dissolution from
liquisolid tablets
HER and OER Activity of Ti4O7@Ti Mesh—Fundamentals Behind Environmental Application
No full textTitanium suboxide (TSO) catalysts offer remarkable activity toward pollutant degradation due to their stability at positive potentials, which enables the formation of reactive oxygen species. Herein, TSOs are prepared directly on the surface of Ti mesh, which also serves as the current collector. The evolution of different TSO surface species during temperature treatment is monitored using micro-Raman spectroscopy. The electrochemically active surface area is determined using cyclic voltammetry (CV) and shows a decrease from 9.3 cm2 to 1.1 cm2 upon increasing temperature, corresponding to the transformation of TSO as seen in micro-Raman spectroscopy. Impedance spectroscopy revealed nearly identical values (≈29 Ohm) for the charge transfer resistance during OER, indicating the presence of the same active centers on the surface. The electrode potential window toward water splitting is examined using oxygen and hydrogen evolution reactions (OER and HER). The Tafel slopes are in the range 400–600 mV dec−1 for OER and 340–440 mV dec−1 for HER, with higher values being desirable in pollutant degradation applications. Onset potential shifted to slightly more negative values with increasing temperature treatment, with samples treated at 850 °C and 950 °C enabling almost tenfold higher currents at the same potential values. The hydrogen evolution potential lies within the optimal region for H* radical formation around −1.2 V vs. RHE. Surface-formed TSOs represent promising biofunctional materials for pollutant degradation
Prospective Risk Management in the Process of Clinical Studies in the Republic of Serbia
No full textBackground: In Serbia, as well as worldwide, clinical trials are a significant and unavoidable part of the development of new medicines. There is limited research on prospective risk management in clinical trials in Serbia, underscoring the need for systematic approaches, such as the failure mode and effects analysis (FMEA) method. The effectiveness of this complex process largely depends on knowledge and experience in the field of management. Like any other process, clinical trials are subject to various risks for both the company and the patient. Purpose: The purpose of this article is to conduct a prospective, qualitative study on the risk management of clinical trials in the Republic of Serbia, to identify, assess, and reduce risks for both patients and companies, and to offer corrective measures for reducing their frequency and consequences. Materials and Methods: A focus group applied the FMEA method to identify, assess, and mitigate risks. Each risk was assessed based on severity, probability, and detectability, and then a risk priority number (RPN) value was calculated. For the most significant risks, corrective measures were proposed, and the RPN was recalculated. The research was conducted from December 12, 2022 to March 8, 2023. Results: In total, 20 risks were identified with RPN values ranging from 10 to 192, of which five had RPN > 100. The minimum RPN value among the five most significant risks was 105, and the maximum was 192. After the proposed corrective measures, there was a significant reduction in the RPN values across all five risks, ranging from 57.14% to 83.33% when compared to the initial values. Conclusion: The FMEA method has proven to be a useful instrument not only for identifying and predicting potential risks, but also for their control
Protective Effects of Curcumin and Sulforaphane Against Ionising Radiation–Induced Oxidative Stress and Inflammatory Responses in Rat Lung Tissue
No full textIonising radiation-induced lung injury is a major complication of thoracic radiotherapy, primarily driven by oxidative stress and inflammation. The current study evaluates and compares the protective effects of sulforaphane (SFN) and curcumin (CUR) pretreatment against radiation-induced oxidative damage and inflammation in rat lung tissue. Female Wistar rats were pretreated in vivo with SFN (2 mg/kg b.w./day) or CUR (4.13 mg/kg b.w./day) for 28 days per os. Isolated lung tissues were exposed ex vivo to γ-radiation (absorbed dose: 2 Gy). Oxidative stress markers—malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl (SH) groups, reduced glutathione (GSH), and superoxide dismutase (SOD)—and inflammatory markers—tumour necrosis factor alpha (TNF-α), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)—were measured to evaluate irradiation and protective effects. Radiation significantly increased MDA, TNF-α, PTGS2/COX-2, and IL-6 levels while decreasing SH groups. Pretreatment with SFN or CUR attenuated these changes. CUR showed a more pronounced effect on oxidative stress-related parameters, whereas SFN more strongly influenced inflammatory markers. These findings suggest that SFN and CUR differentially modulate radiation-induced oxidative and inflammatory responses in lung tissue under the applied experimental conditions and warrant further investigation of their potential as protective agents in radiotherapy
Tackling the interplay between the brain and kidneys: CYP2C19 mice as a preclinical tool for studying cognitive impairment in kidney disease?
No full textChronic kidney disease (CKD) is a global health issue, often associated with cognitive and behavioural disturbances. The cytochrome P450 enzyme CYP2C19 has previously been associated with neurobehavioural changes. Humanised transgenic CYP2C19 mice show emotional changes, and abnormalities in locomotion and in brain regions involved in memory and stress response. This study aimed to investigate whether cognitive impairments in CYP2C19 transgenic mice are related to impaired renal function or structure. Adult male and female wild-type and CYP2C19 mice (total N = 41) were included in the study. Behavioural phenotyping was performed by examining short-term memory in Novel Object Recognition Test (NORT) and social interaction in Social Recognition Test (SRT). After 24 h, urine was collected, animals were sacrificed, and blood samples and kidneys were collected and used for biochemical assays and histological assessment. NORT and SRT revealed cognitive deficits and possible social anxiety in CYP2C19 mice compared to wild-type controls, as no difference was observed in time CYP2C19 mice spent interacting with novel objects or unfamiliar animals. Biochemical analysis showed no significant differences in total protein, albumin, urea, creatinine and uric acid between experimental groups. Histological evaluation confirmed that there was no structural kidney damage in CYP2C19 mice. Our findings indicate that in CYP2C19 mice, cognitive and behavioural changes described here are independent of renal dysfunction. Therefore, CYP2C19 mouse model represents a valuable tool to study cognitive impairment without concomitant kidney disease and could serve as a suitable control in studies investigating the interplay between cognitive decline and CKD