Sinan Gönüllü

This study aims to examine the impact of fecal extracellular vesicles (EVs) derived from laboratory mice on lipopolysaccharide (LPS)-induced neuroinflammatory responses in BV2 microglia cells. EVs were isolated using size exclusion chromatography (SEC) and characterized through transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot techniques. TEM analysis demonstrated characteristic vesicular morphology, NTA confirmed particle distribution within the nanometer size range, and Western blot analysis indicated flotillin positivity while calnexin was absent as a negative control, thereby validating EV purity. 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) assay for dose optimization in BV2 microglia cells revealed that a concentration of 10 µg/mL was cytotoxic; therefore, 2.5 µg/mL and 5 µg/mL were selected as safe doses for further investigations. The effects of EV administration on LPS-induced inflammatory responses were assessed using RT-qPCR and ELISA. In addition, the expression levels of neuroinflammation- and microglial activation-related markers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and triggering receptor expressed on myeloid cells 2 (TREM2), were also analyzed. The findings indicated that EV treatment markedly inhibited the production of pro-inflammatory mediators, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In addition, fecal EV treatment attenuated the LPS-induced elevation of the anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1). Furthermore, changes in the expression of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and triggering receptor expressed on myeloid cells 2 (TREM2) supported the modulation of microglial activation and neuroinflammatory processes by EVs. In conclusion, fecal EVs may modulate neuroinflammatory responses by influencing microglial inflammation and could serve as functional communication mediators within the microbiota-gut-brain axis.

Benign Paroksismal Pozisyonel Vertigo (BPPV), kısa süreli ancak şiddetli vertigo ataklarıyla seyreden ve periferik vertigonun en sık nedenlerinden biridir. Bu çalışmanın amacı, BPPV tanısı alan bireylerde serum 25-hidroksi vitamin D düzeylerini, vertigo öyküsü bulunmayan sağlıklı bireylerle karşılaştırmak ve aradaki farkın istatistiksel önemini değerlendir-mektir. Retrospektif olgu-kontrol tasarımında yürütü-len çalışmaya, yalnızca BPPV tanısı konmuş 2094 hasta ile son bir yıl içinde vertigo veya denge bozuk-luğu öyküsü bulunmayan 2094 sağlıklı kontrol dahil edilmiştir. Kronik sistemik hastalığı olanlar ve D vitamini takviyesi kullanan bireyler çalışma dışı bırakılmıştır. BPPV grubunun yaş ortalaması 46,34 ± 0,34 yıl, kontrol grubunun ise 47,35 ± 0,29 yıl olup gruplar arasında yaş ve cinsiyet açısından anlamlı fark saptanmamıştır. Serum 25-OH D düzeyleri BPPV grubunda 20,13 ± 4,26 ng/mL, kontrol grubun-da ise 25,90 ± 0,32 ng/mL olarak bulunmuş ve bu fark istatistiksel olarak anlamlıdır (p

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the central nervous system and is the most common form of dementia in the elderly. Current diagnostic methods are limited in the early and definitive diagnosis of the disease, necessitating the need for new and more reliable biomarkers. Circular RNAs (circRNAs) are non-coding, single-stranded, and highly stable RNA molecules commonly found in the eukaryotic transcriptome. Recent studies have shown that changes in the expression levels of circRNAs may play a role in AD pathogenesis. Furthermore, these molecules are considered as potential non-invasive biomarkers for early diagnosis of AD. In this study, we comprehensively assessed plasma levels of classical neurodegenerative biomarkers [amyloid-β42/amyloid-β40 (Aβ42/Aβ40) ratio, total Tau (tTau), and phosphorylated Tau (pTau)], as well as glial and inflammatory mediators, TAM receptor family members (Tyro3 and AXL), and the newly identified circular RNA molecule hsa_circ_003077. The findings revealed that the expression levels of TAM receptors were significantly increased, the Aβ42/Aβ40 ratio decreased, and both total Tau and phosphorylated Tau levels were significantly increased in AD patients. In the receiver operating characteristic (ROC) curve analysis performed to determine the diagnostic potential of hsa_circ_003077, the area under the curve (AUC) was 0.90 (95% CI: 0.82–0.97). This high AUC value suggests that hsa_circ_003077 may be a strong and novel biomarker candidate for the non-invasive diagnosis of AD. The data obtained confirmed the diagnostic efficacy of classical AD biomarkers and revealed that hsa_circ_003077 is a promising biomarker for early and accurate detection of the disease. However, in order to assess the transferability of these findings to clinical practice, confirmatory studies with larger sample groups are needed to ensure reproducibility of the results.

Background/Objectives: Alzheimer’s disease (AD) is characterized by progressive neurodegeneration driven by interconnected mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, synaptic impairment, and abnormal protein aggregation. MicroRNAs (miRNAs) have emerged as post-transcriptional regulators of these complex pathways; however, efficient delivery remains a major limitation. Small extracellular vesicles (sEVs) have been proposed as biologically compatible carriers for miRNA delivery. Methods: In this study, milk-derived sEVs were isolated, characterized, and loaded with microRNA-137-5p (miR-137-5p). Their effects were evaluated in an amyloid-β (Aβ)-induced in vitro AD model using SH-SY5Y human neuroblastoma cells. Oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and glutathione peroxidase 1 (GPX1), were assessed. Inflammation- and neuroprotection-related gene expression analyses included intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor alpha (TNF-α), and brain-derived neurotrophic factor (BDNF). Cytoskeletal injury was evaluated using neurofilament light chain (NfL). Mitochondrial stress markers included cytochrome c (Cyt-c), 8-hydroxy-2′-deoxyguanosine (8-OHdG), PTEN-induced kinase 1 (PINK1), dynamin-1-like protein (DNM1L), and mitochondrial transcription factor A (TFAM). Synaptic and extracellular matrix-associated proteins, including complexin-2 (CPLX2), SPARC-related modular calcium-binding protein 1 (SMOC1), and receptor tyrosine kinase-like orphan receptor 1 (ROR1), as well as AD-related biomarkers, including total tau, phosphorylated tau at threonine 181 (pTau-181), phosphorylated tau at threonine 217 (pTau-217), and amyloid-β 1–40 (Aβ1–40), were evaluated using molecular and biochemical approaches. Results: Aβ exposure was associated with increased oxidative stress, inflammatory activation, mitochondrial and cytoskeletal alterations, synaptic-related disturbances, and elevations in tau- and amyloid-associated proteins. Treatment with unloaded sEVs was associated with partial modulation of several parameters, whereas miR-137-5p-loaded sEVs were consistently associated with normalization of multiple pathological markers toward control levels. Conclusions: These findings indicate that miR-137-5p-enriched sEVs may represent a useful experimental platform for multi-target modulation of AD-related cellular alterations. Further mechanistic and in vivo studies are required to clarify translational relevance.

Aim: Loss of balance can be seen in idiopathic Parkinson's disease (IPD) There are only a few studies in the literature in which brainstem involvement in IPD has been researched with neurophysiological tests such as vestibular evoked myogenic potential (VEMP). In this study, it was investigated whether there is a difference in the results of VEMP testing in early or late stage of IPD. Material and method: The IPD cases were classified as early stage and late stage according to the Hoehn-Yahr scale. The presence of a positive wave with a latency of P13 and a negative wave with a latency of N23 was investigated as the first reflex response The latencies of these potentials and the absolute amplitude of the P13-N23 component were measured. The VEMP results of the patients with early and late stage IPD were compared with those of the control group. Results: The right P13 latency mean value in the late stage patient group was significantly prolonged than in the early stage patient group and the control group. The right P13-N23 amplitude mean value of the late and early stage patient groups was significantly smaller than that of the control group (p < 0.002 and p < 0.001, respectively). Among the patients with IPD, the P13 latency was statistically increased in those with a fall history than in those without a fall history. In conclusion, this study indicates that the VEMP pathway is affected over time especially in patients with late stage Parkinson’s disease.