Yazarlar

  • MakaleAçık Erişim2025
    Inhibition of thioredoxin reductase 1 by evernic and vulpinic acids: a promising anticancer strategy on A549 cells

    Günaydın, Şükran; Kalın, Şeyda Nur; Sulukoğlu, Emine Karaca; Altay, Ahmet; Budak, Harun

    TrxR1 (Thioredoxin reductase 1) is overexpressed in several types of cancer, containing lung cancer, which is closely linked to metastasis. Hence, TrxR1 has emerged as a target for cancer therapies. In this study, it was aimed to survey whether lecanoric (LA), evernic acid (EA), and vulpinic acid (VA) exert an anticancer effect on lung cancer (A549) cells by targeting the TrxR1 protein. The findings indicated that VA elicited a more notable cytotoxic activity in A549 cells (36.21 µg/mL) at a lower IC50 value than EA (139.09 µg/mL). Whereas, LA exhibited very low cytotoxic effect in A549 cells. The flow cytometry and qPCR analyses revealed that VA was superior to EA in inducing apoptosis and necrosis in A549 cells. Moreover, the wound healing assay revealed that both EA and VA considerably inhibited the migration of A549 cells. Furthermore, EA and VA markedly decreased protein expression and enzyme activity of TrxR1 in A549 cells. All these findings revealed that EA and VA possess anticancer activities by targeting TrxR1 in A549 cells. Hence, EA and VA can be proposed as candidates for use as a potential chemotherapeutic agent for lung cancer.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleYayıncıda açık erişim2025
    Investigating the therapeutic potential of transcranial direct current stimulation in an experimental Parkinson’s model through glutamate pathway

    Danisman, Betul; Sinen, Osman; Sinen, Ayşegül Gemici; Çiçek, Betül; Derin, Narin; Akçay, Güven; Hacimüftüoğlu, Ahmet

    The study’s objective was to look into the glutamate-mediated therapeutic effects of tDCS, which is known to modulate motor cortical plasticity and is thought to be a potential alternative treatment for Parkinson’s disease (PD), in 6-hydroxydopamine (6-OHDA) lesion rats with behavioral changes. Following tDCS application (0.5 mA anodal and cathodal tDCS, 30 min/day, 5 days/week, starting 7 days after the PD lesion) in PD animals, the effects of treatment on motor and non-motor behaviors as well as the glutamatergic pathway were determined. Four groups were conducted: Sham, PD, PD + A-tDCS (anodal stimulation) and PD + C-tDCS (cathodal stimulation). Apomorphine-induced rotation test, cylinder test, open field and new object recognition tests were performed. Glutamate, NMDA and EAAT2 levels were evaluated in the total hippocampus, prefrontal cortex and substantia nigra tissues. We found that tDCS treatment, regardless of anodal or cathodal, significantly attenuated 6-OHDA-induced motor activity deficits, as measured in open field test, apomorphine-induced rotations, and cylinder test performances, and was also effective in new object recognition memory. Glutamate and NMDA levels increased in the hippocampus, prefrontal cortex and substantia nigra tissues, while EAAT2 levels decreased in the PD group. tDCS application was significantly alleviated the effects of 6-OHDA. These results suggest that tDCS application can improve the aggravation of locomotor activity and learning performance, and exhibit neuroprotective effects through glutamate, NMDA and EAAT2 in PD rat model.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    A New Emerging Threat in Critical Care: Myroides odoratimimus Outbreak in a Tertiary Hospital

    Savci, Unsal; Eser, Baris; Sungur, Mustafa; Yildiz, Serap S.; Akdogan, Ozlem; Caliskan, Selahattin; Sahin, Mustafa

    Aims and background:Myroides spp. is an environmental pathogen and causes disease in immunocompromised patients. In this study, we report an outbreak of urinary tract infections (UTIs) caused by Myroides odoratimimus (M. odoratimimus) in a university hospital in Turkey. Methods: A total of 25 M. odoratimimus strains isolated from the clinical samples of 20 patients in our intensive care units and clinics were included in the study. Phenotypic and genotypic identification of isolates was performed using conventional methods, VITEK®-2 automated identification system, Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry, and 16S-RNA Microbial Diagnosis methods. In addition, the repetitive extragenic palindromic (REP) elements polymerase chain reaction (PCR) assay method was applied for molecular epidemiological analysis. Results: All cases were diagnosed with nosocomial UTI, except for one case diagnosed with nosocomial bacteremia. One of the M. odoratimimus isolates was sensitive to piperacillin/tazobactam (MIC: ≤4 µg/mL), and one isolate was moderately sensitive to cefepime (MIC: 16 µg/mL). Other all M. odoratimimus isolates were resistant to the tested antibiotics beta-lactams, monobactams, carbapenems, aminoglycosides, fluoroquinolones, and sulphonamides. When 10 isolates were evaluated with the REP PCR method, DNA fingerprint similarities were visually determined, and there was a similar DNA pattern among them. The source of Myroides infection could not be identified from the environmental samples. Conclusions: The increasing population of immunosuppressed patients suggests that M. odoratimimus and other opportunistic multi-drug resistant pathogens with resistance to broad-spectrum antibiotics may be encountered more frequently in critical units in future. In order to choose the optimal antibiotic regimen, awareness and an index of suspicion regarding this atypical pathogen are important for rapid identification and appropriate susceptibility testing. Clinical significance: It has been observed that the pathogenicity of M. odoratimimus bacteria has increased recently, and it can not only cause UTIs but more serious manifestations such as sepsis with bacteremia, which can be life-threatening.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Maternal readiness for weaning: Influencing factors and determinants; [Prontidão materna para o desmame: fatores influentes e determinantes]; [Preparación materna para el destete: factores influyentes y determinantes]

    Akça, Kamile; Kekil, Songül; Özcan, Meltem

    Objective: To assess maternal readiness for weaning and examine the socio-demographic and behavioral factors influencing weaning decisions. Method: A cross-sectional study was conducted at three Family Health Centers located in a provincial center between October 2024 and January 2025. The study included 202 breastfeeding mothers. Data were collected through face-to-face interviews using a sociodemographic questionnaire and the validated Readiness for Weaning Scale. Statistical analyses included t-tests, ANOVA, chi-square tests, and logistic regression. Results: Mothers with higher education had significantly higher scale scores than those with lower education. Breastfeeding education was associated with increased weaning readiness. Planned pregnancy and maternal perception of milk sufficiency were positively correlated with higher scale scores. Smoking was associated with lower readiness. Logistic regression indicated that maternal perception of milk sufficiency significantly predicted weaning consideration, while lower education levels were associated with reliance on traditional weaning methods. Traditional weaning methods referenced in this study include culturally ingrained practices such as abrupt cessation, use of herbal substances, or application of unpleasant tastes to the breast. Conclusion: Maternal education, psychological preparedness, and professional support play key roles in structured weaning. Targeted interventions are needed to enhance maternal confidence and informed decision-making in infant feeding transitions. Limitations of the study include its cross-sectional design, which prevents causal inference, and the reliance on self-reported data, which may be subject to recall or social desirability bias.

    • SDG 2 · Açlığa Son
    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Key predictors of mortality in Crimean-Congo haemorrhagic fever: a retrospective multicentre cohort study

    Güllü, Deniz; Yigci, Defne; Baykam, Nurcan; Çelikbaş, Aysel Kocagül; Yapar, Derya; Akdoğan, Özlem; Özden, Kemalettin; Sarıkaya, Rukiye İnan; Hasanoğlu, İmran; Güner, Rahmet

    Objective This study aimed to identify key predictors of mortality in patients with Crimean-Congo haemorrhagic fever (CCHF). Our specific goals included characterizing the demographic and clinical features of hospitalized CCHF patients in Türkiye, determining the factors associated with mortality among these patients, and evaluating the impact of early ribavirin administration. Methods A retrospective study was conducted on 1103 CCHF patients across 18 hospitals in Türkiye from 1 January 2019 to 20 November 2024. All data were obtained via an online data collection system by the designated physician at each centre. Patients with laboratory-confirmed CCHF infection who were hospitalized were included in the study. Univariate analyses and time-dependent Cox regression were conducted. Results Of the 1103 patients, 65.7% (725/1102) were men; 87.2% (962/1103) resided in rural areas; and the mean age was 53 years. Ticks were identified as the transmission route in 68.4% (755/1103) of the cases. Comorbidities included diabetes mellitus, chronic heart disease, and hypertension; 4.6% (51/1103) of the patients developed healthcare-related infections. Intensive care unit admission was required in 8.0% (88/1103) of the patients, and the overall mortality rate was 5.1% (56/1103). In univariate analyses, age ≥50 years (odds ratio [OR], 3.1; 95% CI, 1.58–6.08; p < 0.001) and diabetes mellitus (OR, 4.49; 95% CI, 2.20–9.18; p < 0.001) were associated with increased mortality. Both variables remained statistically significant predictors in the multivariate analysis. Although early ribavirin administration, ≤96 hours from symptom onset, did not reach statistical significance in univariate analysis (OR, 0.52; 95% CI, 0.26–1.05; p = 0.065), it was significantly associated with reduced mortality in time-dependent Cox regression (adjusted hazard ratios, 0.21; 95% CI, 0.07–0.69; p = 0.010). Discussion Key factors such as age and comorbidities can predict mortality in CCHF patients. Timely identification of these predictors, along with early administration of ribavirin, may contribute to improved survival and better clinical outcomes.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleYalnız künye2025
    Thiophene-based hydrazones and their metal complexes: Synthesis, structure affirmation, antioxidant and cytotoxic activity, photoluminescence, molecular docking, and ADMET studies

    Sarıoğlu, Ahmet Oral; Bulut, Zafer; Türkmenoğlu, Burçin; Yumrutaş, Pınar; Mısır, Büşra Albayrak; Karaküçük-İyidoğan, Ayşegül; Oruç-Emre, Emine Elçin

    This work involves the synthesis of N'-(2‑hydroxy-3‑methoxy-5-nitrobenzylidene)thiophene-2-carbohydrazide (HL1) and N'-(2‑hydroxy-5‑methoxy-3-nitrobenzylidene)thiophene-2-carbohydrazide (HL2) and their complexes with Cu(II), Ni(II), and Fe(II), as well as the investigation of their photoluminescence properties, cytotoxic, and antioxidant activities. Elemental analysis, molar conductivity, FT-IR, UV–Vis, TGA, LC-MS/MS, and 1H and 13C NMR (only for ligands) were used to determine the chemical structures of all compounds. Two complementary tests (CUPRAC and DPPH assays) were used to evaluate the antioxidant activities of the compounds. The results suggested that compound [Fe(L2)2] (L2-Fe) was found to have good radical scavenging power compared to α-tocopherol in the CUPRAC assay. The newly synthesized thiophene-based hydrazones and their metal complexes were screened for in vitro cytotoxic activity assessments against A549 and BEAS-2B cell lines and were found to show high cellular toxicity at lower doses on the A549 cell line. In particular, the Cu(II) complexes ([Cu(L1)2] (L1–Cu) and [Cu(L2)2] (L2–Cu)) exhibited the inhibitory effect against A549 cells with IC50 values of 5.1 and 6.93 μM, respectively. In order to the anticancer and antioxidant effects of the active compounds, the possible interaction mechanisms between novel compounds and target proteins were performed computationally by the molecular docking study. In conclusion, the study provided preliminary information about some biological properties of ligands and their Cu(II) complexes. It revealed that thiophene-based hydrazones may play a crucial role in drug applications. Also compounds that could be drug candidates were compared with both experimental and computational data.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    The role of antioxidant and anti-inflammatory mechanisms in the protective effects of vigabatrin against ovarian ischemia-reperfusion injury in a rat model

    Hizal, Elif; Uyar, Esra; Bingul, Eda; Cicek, Betul; Demir, Özlem; Mammadov, Renad; Sarigul, Cengiz; Gursul, Cebrail; Suleyman, Halis

    Background: Exposure of ovarian tissue to ischaemia and subsequent reperfusion can result in oxidative and inflammatory damage. A decline in adenosine triphosphate (ATP) levels has the potential to initiate pathological processes and compromise antioxidant defence mechanisms. Vigabatrin, an antiepileptic agent, has been shown to increase levels of gamma-aminobutyric acid (GABA). GABA has the potential to increase ATP levels. The present study was conducted to evaluate the preventive effects of vigabatrin concerning ovarian ischaemia-reperfusion (I/R) injury. Methods: The experiment comprised the allocation of thirty female Wistar albino rats into five groups: a sham operation group (SOG), a vigabatrin group (VIG), an ovarian I/R group (OIR), a vigabatrin + sham operation group (VISO), and a vigabatrin + ovarian I/R group (VOIR). Surgical procedures were performed under anesthesia. The VIG and VOIR were given vigabatrin (50 mg/kg, orally). Following a period of anticipation spanning an hour, the ovaries of the SOG, OIR, and VOIR rats were accessed via an abdominal incision. The incision site was sutured without the performance of an I/R procedure on the SOG ovaries. In the OIR and VOIR, the right ovaries were subjected to three hours of ischemia, followed by six days of reperfusion. Drug treatment was administered once a day using the same method for six days. Then, the rats were euthanised with 120 mg/kg ketamine (intraperitoneally). The ovarian tissues were removed. These samples were examined for oxidants, antioxidants, and proinflammatory cytokines. Results: The I/R procedure caused an increase in malondialdehyde, tumour necrosis factor alpha, interleukin 1β, and interleukin 6 levels, as well as a diminish in total glutathione, superoxide dismutase, and catalase in the ovaries, compared to the SOG (p < 0.001). Moreover, in the present study, I/R was found to result in changes in follicle numbers, as well as congestion, dilatation of the vessels, edema, and an increase in inflammatory cells (p < 0.05). In comparison with OIR, VOIR demonstrated a decline in oxidants and proinflammatory cytokines, an augmentation in antioxidants, and a reduction in histopathological damage(p < 0.05). Conclusion: It is proposed that vigabatrin may represent a novel strategy for the prevention of ovarian injury associated with I/R. Clinical trial number: Not applicable.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Molecular and structural characterization of ureido-benzenesulfonamides as dual inhibitors of aldose reductase and cholinesterases

    Türkeş, Cüneyt; Lolak, Nebih; Duran, Hatice Esra; Yapar, Gönül; Akocak, Suleyman

    The conformational and kinetic intricacies of enzyme-ligand interactions are critical for understanding molecular mechanisms underlying metabolic and neurodegenerative pathologies. Herein, we report a rationally designed series of ureido-benzenesulfonamides as dual-acting nanomolar inhibitors targeting aldose reductase (ALR2) and cholinesterases (AChE and BChE). Spectrophotometric inhibition assays revealed that compound 3SA-a displayed exceptional ALR2 affinity (KI = 7.00 ± 0.68 nM), surpassing epalrestat by over 30-fold. Likewise, 3SA-f selectively inhibited BChE with a KI of 24.20 ± 2.26 nM, outperforming tacrine by a factor of 7.8. Molecular docking simulations highlighted distinct dynamic binding modes: 3SA-a engaged ALR2's catalytic cleft through a hydrogen bond with Tyr48 and water-bridged interactions, whereas 3SA-f leveraged π-π stacking and halogen bonding within BChE's extended acyl pocket. These binding orientations were consistent with SAR findings, where meta-sulfonamide placement and halogen substitution optimized selectivity and conformational complementarity. Complementary in silico ADME-Tox predictions confirmed the drug-like nature of all compounds (0 Lipinski/PAINS violations), moderate oral permeability (QPPCaco: 79–85 nm/s), and low CNS exposure (CNS score = −2), aligning with a peripheral mechanism of action. Collectively, this study provides a detailed structural and dynamic framework for dual-target enzyme inhibition, offering a tunable scaffold for future therapeutics targeting the ALR2-ChE axis.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Effects of adenosine triphosphate, thiamine pyrophosphate, melatonin, and liv-52 on subacute pyrazinamide proliferation hepatotoxicity in rats

    Ciftel, Sedat; Ciftel, Serpil; Altuner, Durdu; Huseynova, Gulbaniz; Yucel, Nurinisa; Mendil, Ali Sefa; Sarigul, Cengiz; Suleyman, Halis; Bulut, Seval

    Background: Hepatotoxicity of pyrazinamide, an antituberculosis drug, limits its therapeutic use and oxidative stress has been implicated in this toxicity. This study investigated the protective effects of adenosine triphosphate (ATP), thiamine pyrophosphate (TPP), melatonin, and Liv-52, which have previously been shown antioxidant activities, on pyrazinamide-induced hepatotoxicity. Methods: 36 albino Wistar male rats were divided into randomized six groups; healthy (HG), pyrazinamide (PZG), ATP + pyrazinamide (APZG), TPP + pyrazinamide (TPZG), melatonin + pyrazinamide (MPZG) and Liv-52 + pyrazinamide (LPZG) groups. ATP 4 mg/kg and TPP 25 mg/kg were administered intraperitoneally (IP). Melatonin 10 mg/kg and Liv-52 20 mg/kg were given orally. One hour after administration of ATP, TPP, melatonin, and Liv-52, 250 mg/kg pyrazinamide was applied orally to all rats except HG group. The treatment was repeated (1 × 1) for 4 weeks. Then, blood samples were taken for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Immediately after, the rats were euthanized with thiopental sodium (50 mg/kg, IP), and the livers were removed. The tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) also hydropic degeneration, necrosis, and apoptosis (caspase 3) were examined.One-Way ANOVA was used in biochemical analyses and Tukey test was used as post-hoc. For histopathological and immunohistochemical analysis, the Kruskal-Wallis test was used and Dunn’s test as a post-hoc. Results: Pyrazinamide increased MDA land decreased tGSH, SOD, and CAT levels in liver tissues (p < 0.001). It also increased serum ALT and AST activities and caused severe hydropic degeneration and necrosis in liver tissue (p < 0.001). ATP, TPP, melatonin, and Liv-52 significantly prevented the biochemical and histopathological changes induced by pyrazinamide (p < 0.05). On the other hand, Liv-52 was more successful than other potential protectors in protecting liver tissue from pyrazinamide damage (p < 0.05). Conclusions: ATP, TPP, melatonin, and Liv-52 can be used to protect liver tissue from pyrazinamide-induced hepatotoxicity in rats.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    EFFECT OF LAMOTRIGINE SOLID DISPERSIONS ON VIABILITY OF A549 AND RG-2 CELLS; [LAMOTRİJİN KATI DİSPERSİYONLARININ A549 VE RG-2 HÜCRELERİNİN CANLILIĞI ÜZERİNE ETKİSİ]

    Pezik, Esra

    Objective: LMT is an antiepileptic drug that is among the drugs being repositioned/reprofiled beyond its original medical indications, thanks to its promising anticancer activity profiles on various cancer cells. In this study, the improvement of the poor aqueous solubility of LMT using solid dispersion technique with different polymeric/surfactant carriers in different ratios and the antiproliferative effect potentials of the obtained optimum LMT solid dispersion on A549 and RG-2 cells were determined. Material and Method: LMT solid dispersions were prepared using four different carrier types (PEG 4000, PEG 6000, poloxamer 188 and poloxamer 407) and five different drug to carrier ratios (1:2-1:4-1:6-1:8-1:10) according to the melting method and the change in the solubility profile was determined by solubility studies performed according to the shake-flask method. The MTT assay protocol was used to determine the cytotoxicity profile of the selected optimum solid dispersion (F8) on A549 and RG-2 cell lines. The interaction of LMT with the formulation components and the solid-state characteristics within the formulation were evaluated by XRD, DSC, FTIR, and SEM analyses. Result and Discussion: The solubility studies showed that LMT exhibits a pH-dependent solubility profile, and the highest solubility increase (2.3 fold) in solid dispersion formulations was obtained with the F8 formulation using poloxamer 407 at a 1:6 ratio. XRD, DSC, FTIR, and SEM analysis results explain the partial amorphization of LMT in the F8 formulation. In vitro cytotoxicity studies have shown that LMT has a dose-dependent antiproliferative effect on RG-2 cells, but no significant cytotoxic effect at low doses (10-80 µg/ml). For A549 cells, cell viability decreased with increasing doses, suggesting promising results regarding antiproliferative effects at higher doses.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Phytochemical Traits and Biological Activity of Satureja hortensis and Satureja macrantha as Culinary Spices Using GC–MS/MS and LC–MS/MS Techniques

    Elmdoustazar, Pardis; Aydın, Bilge; Önal, Mehmet; Yuca, Hafize; Karadayı, Mehmet; Gülşahin, Yusuf; Demirci, Betül; Karakaya, Songül; Güvenalp, Zühal

    This study evaluates the antidiabetic, anti-Alzheimer, antimicrobial, and antioxidant activities of water and methanol extracts, as well as essential oils, from Satureja macrantha and Satureja hortensis. Chemical characterization was conducted using LC–MS/MS for phenolic profiles and GC–MS for essential oil composition. Biological activities were assessed via DPPH˙ and ABTS˙+ assays for antioxidant capacity, α-glucosidase and α-amylase inhibition for antidiabetic potential, cholinesterase inhibition for anti-Alzheimer activity, and the microdilution method for antimicrobial effects. Genotoxicity and antigenotoxicity were evaluated using Ames and Allium cepa assays. Rosmarinic acid was most abundant in S. macrantha water extract (50.687.02 ng/mL), while thymol (45.1%) and p-cymene (45.8%) were identified as major oil components. S. hortensis essential oil showed the strongest α-glucosidase (41.33%) and butyrylcholinesterase inhibition (35.68%), whereas S. macrantha oil exhibited higher acetylcholinesterase inhibition (16.05%). Antioxidant activity was most pronounced in S. macrantha water extract (ABTS˙+: 52.11%, DPPH˙: 28.76%). S. hortensis essential oil demonstrated the most effective antimicrobial properties. These findings suggest that both S. macrantha and S. hortensis could be recommended as safe and effective candidates for use in the development of natural therapeutic agents.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Synthesis, molecular docking, and antiproliferative activity studies of bromine bearing Schiff bases

    Karatas, Halis; Turkmenoglu, Burçin; Kokbudak, Zülbiye; Akkoc, Senem

    Bromine-bearing compounds are found in a variety of natural products and synthetic drugs and exhibit a variety of biological activities. They often display particular properties such as enhanced stability, improved lipophilicity, and larger molecular interactions, making them valuable in drug design and development. In this study, three bromine-bearing Schiff bases were synthesized, characterized, and tested in lung (A549) and colon (DLD-1) cancer cell lines for 72 h incubation time. The results demonstrated that compounds had antiproliferative activity in screened cell lines. The compounds were also tested on a healthy embryonic kidney cell line (HEK-293T) to evaluate their toxic effects on non-cancerous cells. In vitro results of compounds interacting with the most suitable target were confirmed by in silico approaches. All bromine-containing compounds were interacted with the receptor tyrosine kinase FLT3 target via molecular docking. From the interaction results of the 6JQR crystal structure with 2-Br, the docking score value was calculated as −8.178 kcal/mol, and this value was determined to be better than the docking score (−7.269 kcal/mol) value of gilteritinib. Pharmacokinetics, toxicity properties and Lipinski violations of the compounds were estimated by ADMET and were calculated to be in the range of recommended values. Molecules demonstrated limited efficacy against A549 cells line, however; they exhibited relatively greater effectiveness against DLD-1 cell line. Notably, the IC50 value of 2-Br was comparable to that of cisplatin. All molecules exhibited minimal toxicity.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleYalnız künye2025
    Design and Evaluation of the PLGA Nanoparticles Containing Ketorolac Tromethamine in Glioblastoma Treatment

    Çopur, Tuğba; Kurt, Nihat; Pezik, Esra; Yalçın, Doruk; Bozdağ Pehlivan, Sibel; Öner, Levent

    The blood–brain barrier (BBB) separates blood from brain tissue, making drug delivery to the brain a significant challenge. This study aims to develop and optimize a novel nanoparticle system that may overcome the BBB and have a potential effect on glioblastoma. Ketorolac tromethamine (KT)-loaded poly(lactic-co-glycolic acid) (PLGA) RG 503-H nanoparticles were prepared using water/oil/water (W/O/W) emulsification solvent evaporation. KT-loaded nanoparticles have a particle size of 155.5 ± 2.08 nm, a zeta potential of -12.9 ± 1.23 mV, a polydispersity index of 0.111 ± 0.035, and an encapsulation efficiency of 53.46%. A significant portion of the drug (> 90%) was released in 6 h and completed within 24 h. When 3% (w/v) mannitol and trehalose were used as cryoprotectants, the nanoparticles remained physically stable. Additionally, it has been discovered that KT solution is cytotoxic at high doses to Rat Brain Glioblastoma (RG2) cells, and KT-loaded nanoparticles are more effective than drug solutions at lower doses.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • Derleme MakaleYalnız künye2025
    Herbal drug delivery for ocular treatments—an updated review

    Polat, Heybet Kerem; Tunçel, Emre; Gözcü, Sefa; Turanlı, Yasin; Karakuyu, Nasıf Fatih; Ünal, Sedat

    The aim of this review is to address the challenges faced by traditional dosage forms in ocular herbal drug delivery and to demonstrate the potential offered by nanotechnology to overcome related challenges. This study employed a systematic investigation approach, focusing on nanocarrier systems and advanced material-based strategies documented in the literature. Various nanoformulation systems, including in situ gels, liposomes, ethosomes, transfersomes, exosomes, polymeric and lipid-based nanoparticles, emulsions, nanofibers, and dendrimers, are extensively evaluated. The contribution of innovative nanomaterials, such as nanozymes and metallic and ceramic nanoparticles, to herbal drug delivery is assessed. Different herbal secondary metabolites with potential indications for ocular diseases are reviewed. The reported findings in the literature demonstrate that nanotechnology can enhance the solubility and stability of plant-derived active ingredients, enabling controlled release in target tissues and thus enhancing therapeutic efficacy. Furthermore, safety, toxicity, and regulatory frameworks are scrutinized. In summary, this review highlights the opportunities offered by nanotechnology-based systems in herbal medicine applications and guides integrating of alternative herbal therapies with allopathic approaches in the future.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Thermosensitive in situ gel containing alpha-lipoic acid and rutin for the treatment of corneal neovascularization: formulation, characterization, and in vivo evaluation

    Polat, Heybet Kerem; Karakuyu, Nasıf Fatih; Ünal, Sedat; Turanlı, Yasin; Pezik, Esra; Sofu, Gülşah Usta; Sarman, Emine

    Corneal neovascularization (CnV) is a significant ophthalmological condition often leading to discomfort and vision impairment. Due to the limitations and side effects associated with conventional drug therapies for CnV, innovative treatment strategies are being explored. In this study, the potential of alpha-lipoic acid and rutin-loaded thermosensitive in situ gels for the treatment of CnV was evaluated. The ocular in situ gel was formulated using the cold method and included chitosan, poloxamer 407, and poloxamer 188 as polymers. A design of experiments (DoE) approach was employed to investigate the effects of formulation variables on critical quality attributes, including pH, gelation temperature, and viscosity. The optimized drug-loaded gel exhibited a pH of 5.05 ± 0.1, pseudo-plastic flow behavior with a viscosity of 341 ± 26 cP at 25 °C, and gelation at 34 ± 0.4 °C. Drug release followed Weibull and first-order kinetics. Ocular safety was confirmed through in vitro cytotoxicity studies using L929 and ARPE-19 cell lines. In vivo studies in rats and histochemical analyses of the cornea demonstrated that the optimized formulation (Formulation K) was as effective as dexamethasone, a standard treatment for CnV, and further promoted epithelial cell regeneration. Histological evaluations of ocular tissues revealed reduced inflammation and neovascularization in the Formulation K group, supporting its therapeutic potential. Overall, our findings suggest that the developed in situ gel system offers sustained drug release and enhanced therapeutic efficacy for the treatment of corneal neovascularization.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    EZH2 expression in colorectal carcinoma: an evaluation of clinicopathological and prognostic value

    Cagatay, Diren Vuslat; Balci, Mecdi Gurhan; Issin, Gizem; Demir, Fatih

    Background: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2, catalyzes trimethylation of histone H3 lysine 27 and has been implicated in tumor progression. Aim: Our study aims to assess the relationship between EZH2 expression and clinicopathologic data, and survival in colorectal carcinomas (CRC). Materials and methods: EZH2 immunohistochemistry was performed on tumor blocks from 124 CRC patients. Based on H-scores, cases were stratified into low- and high-expression groups. EZH2 status was correlated with demographic, clinical, and pathologic features, and overall survival was analyzed with the Kaplan–Meier method and log-rank test. Results: A total of 124 cases of CRC; 12 (9.7%) cases were classified as low EZH2 expression, and 112 (90.3%) cases were classified as high EZH2 expression. A significant association was found between EZH2 expression and microsatellite stability. High EZH2 expression was significantly enriched in microsatellite-stable tumors (p = 0.007) and in left-sided lesions (p = 0.049). No significant associations were detected with sex, stage, grade, lymph-node status, or vascular invasion. Kaplan–Meier analysis revealed no difference in overall survival between low- and high-EZH2 groups (log-rank p = 0.47; hazard ratio = 1.13, 95% CI 0.45–2.85). EZH2 staining was uniformly strong in normal mucosa and adenomas, mirroring the high expression observed in most CRCs. Conclusions: EZH2 is highly expressed across the normal-adenoma-carcinoma sequence and, in our cohort, was not linked to overall survival or to most clinicopathologic parameters in CRC. The lower expression observed in a subset of MSI-H tumors warrants further investigation; present evidence remains insufficient to establish EZH2 as an independent prognostic biomarker.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • Derleme MakaleAçık Erişim2025
    High Tibial Osteotomy (HTO), Unicompartmental Knee Arthroplasty (UKA), and Proximal Fibular Osteotomy (PFO) for Medial-Compartment Knee Osteoarthritis: A Narrative Review of Comparative Mechanisms, Clinical Outcomes, and Decision-Making

    Yapıcı, Furkan

    Background: Medial-compartment knee osteoarthritis with varus alignment is treated surgically by realignment (high tibial osteotomy, HTO), resurfacing (unicompartmental knee arthroplasty, UKA), or proximal fibular osteotomy (PFO), which aims to indirectly unload the medial tibial plateau. Methods: We conducted a structured narrative review (PubMed/MEDLINE, Google Scholar; 2000–2025; last search 30 August 2025) of comparative clinical, biomechanical and safety data for HTO, UKA and PFO, including prior meta-analyses and mechanistic reports. One hundred fourteen studies met prespecified criteria. Results: HTO reliably corrects coronal alignment and unloads the medial compartment; long-term survivorship varies by selection and technique, and complications include hinge fracture, delayed/nonunion and hardware problems. UKA typically yields faster early pain relief and recovery in pooled analyses, with implant-specific failure risks and mid-term revision dependent on design and surgical experience. PFO cohorts consistently report early pain and function gains with plausible biomechanical rationale, but evidence is dominated by small, heterogeneous series with short follow-up and limited comparative data. Adjusted head-to-head comparisons generally favor UKA for early pain yet show HTO and UKA can achieve similar patient-reported improvements in selected younger cohorts; robust comparative trials including PFO are lacking. Conclusions: HTO and UKA are established, mechanistically distinct options best matched to patient age, alignment, activity goals, and comorbidity. PFO is a low-burden, promising alternative with uncertain durability; longer-term, controlled evaluation and registry surveillance are required before broad adoption. Findings should inform shared decision-making while acknowledging differences in evidence maturity.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2025
    Examination of PDK1/AKT/mTOR transcription and exosomal mRNA levels in human glioblastoma cell line treated with a combination of temozolomide and hesperidin

    Genc, Sidika; Cicek, Betul

    The most malignant type of tumor in the brain is high-grade gliomas. Glioblastoma (GB), a grade 4 glioma, has the lowest 5-year survival rate and is associated with poor prognosis. An important signaling pathway involved in the pathogenesis of GB is the mammalian target of rapamycin (mTOR). Therefore, our study aimed to investigate how exosomes obtained from GB cells applied with different doses of hesperidin (HSP) affect miR- 9 and change the PDK1/AKT/mTOR pathway. For this purpose, T98G cells were treated with different doses (5, 10, 25, and 50 µg/mL) of HSP in combination with temozolomide (TMZ- 10 µg/mL). At the end of 24 h, cell viability, flow cytometry, and biochemical tests were performed. Additionally, exosomes were isolated from cells belonging to the control, TMZ, and high-concentration TMZ-HSP groups. miR- 9, PDK1, PTEN, AKT- 1, Bax, Bcl- 2, and Caspase 3 genes were expressed in both application groups and exosomes belonging to these groups. HSP was found to reduce the viability of GB cells significantly. The viability was significantly reduced, especially in the TMZ-HSP 50 µg/mL group. Depending on the dose, there was a significant increase in the LDH level and oxidative stress level. The apoptosis level was approximately 26% in the TMZ-HSP 50 µg/mL group. Along with all this, gene expressions changed at the exosomal level, and miR- 9 and miR- 146 levels increased. Similarly, it changed the expression of proteins related to the PDK1/AKT/mTOR signaling pathway at the exosomal level (p < 0.05). In conclusion, the TMZ-HSP combination showed anticancer effects in T98G cells, influenced exosome profiles, and appeared non-toxic and potentially beneficial to healthy cells, highlighting its potential therapeutic value.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • Derleme MakaleAçık Erişim2025
    Emergency radiology: roadmap for radiology departments

    Aydin, Sonay; Ece, Bunyamin; Cakmak, Vefa; Kocak, Burak; Onur, Mehmet Ruhi

    Emergency radiology has evolved into a significant subspecialty over the past 2 decades, facing unique challenges including escalating imaging volumes, increasing study complexity, and heightened expectations from clinicians and patients. This review provides a comprehensive overview of the key requirements for an effective emergency radiology unit. Emergency radiologists play a crucial role in real-time decision-making by providing continuous 24/7 support, requiring expertise across various organ systems and close collaboration with emergency physicians and specialists. Beyond image interpretation, emergency radiologists are responsible for organizing staff schedules, planning equipment, determining imaging protocols, and establishing standardized reporting systems. Operational considerations in emergency radiology departments include efficient scheduling models such as circadian-based scheduling, strategic equipment organization with primary imaging modalities positioned near emergency departments, and effective imaging management through structured ordering systems and standardized protocols. Preparedness for mass casualty incidents requires a well-organized workflow process map detailing steps from patient transfer to image acquisition and interpretation, with clear task allocation and imaging pathways. Collaboration between emergency radiologists and physicians is essential, with accurate communication facilitated through various channels and structured reporting templates. Artificial intelligence has emerged as a transformative tool in emergency radiology, offering potential benefits in both interpretative domains (detecting intracranial hemorrhage, pulmonary embolism, acute ischemic stroke) and non-interpretative applications (triage systems, protocol assistance, quality control). Despite implementation challenges including clinician skepticism, financial considerations, and ethical issues, AI can enhance diagnostic accuracy and workflow optimization. Teleradiology provides solutions for staff shortages, particularly during off-hours, with hybrid models allowing radiologists to work both on-site and remotely. This review aims to guide stakeholders in establishing and maintaining efficient emergency radiology services to improve patient outcomes.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleYalnız künye2025
    Being an Orthopedic Disabled Employee in Public Institutions in Turkey: A Provincial Example

    Polat, Tuncay; Göçer, Şemsinnur

    Background: In this article, the difficulties faced by people with orthopedic disabilities working in public institutions in their working lives are identified and discussed. Objective: This study aims to identify the problems faced by individuals with orthopedic disabilities working in public institutions in their working lives and to offer appropriate solutions to these problems. Methods: In this study, 26 orthopedically disabled individuals working in 17 different public institutions in Erzincan city center in Turkey were included. In the study conducted with qualitative research method, the data were collected with a semi-structured and face-to-face interview form and were created using descriptive analysis method, sub-problems were determined and supported with quotations from the participants. Results: It has been determined that there are deficiencies and inadequacies in the workplaces of orthopedically disabled individuals working in public institutions regarding physical accessibility, harmony between work and employee, workload, the position they work in, the problems they experience with their colleagues and managers, the employment of disabled people in the public sector and the expectations of disabled people and presented as sub-headings. Conclusion: In line with the results, suggestions for solving the problems were presented and thus, it was tried to contribute to the studies to be carried out on the subject.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    • SDG 8 · İnsana Yakışır İş ve Ekonomik Büyüme
    • SDG 10 · Eşitsizliklerin Azaltılması