Gokhan Unal

Macrophage Migration Inhibitory Factor (MIF) is a key inflammatory cytokine implicated in immune regulation and tumour biology. Its role in lung disease, particularly in relation to tumour differentiation and clinical risk, remains incompletely understood. This study aimed to evaluate the expression pattern of MIF in lung disease using gene expression profiling, assess its variation across histological grades, and determine its association with clinical risk. A secondary data-based exploratory analysis was conducted using microarray gene expression data from 442 lung tissue samples obtained from a publicly available dataset. MIF expression was extracted using probe ID 200799_at from the Affymetrix Human Genome U133A platform. Samples stratified based on histological differentiation into well, moderate, and poorly differentiated groups. Statistical analyses included descriptive statistics, Welch’s t-test, Pearson correlation, and linear regression. MIF expression demonstrated a significant increase with decreasing tumour differentiation, with the highest levels observed in poorly differentiated tumours (11.05±0.68). Independent t-tests confirmed significant differences between all histological groups (p<0.05). However, correlation analysis revealed a weak and non-significant association with clinical risk (r=0.06, p=0.20) and regression analysis indicated minimal predictive power (R²=0.003). MIF expression is significantly associated with tumour differentiation in lung disease but lacks predictive value for clinical risk. These findings suggest that MIF serves as a marker of tumour biology rather than a standalone prognostic biomarker.

Background/Objectives: Autism is a complex neurodevelopmental condition characterized by social and cognitive impairments, with growing evidence implicating neuroinflammation, disrupted autophagy, apoptosis, GABAergic dysfunction, and gut permeability in its pathophysiology. Thus, this study aimed to evaluate the independent and combined effects of intermittent fasting (IF) and the next-generation probiotic Akkermansia muciniphila on behavioral outcomes and molecular markers in prenatal valproic acid (VPA)-induced autism model. Methods: Male rat offspring were allocated into five groups (n = 8 per group): control, VPA, IF, probiotic, and IF + probiotic. The groups other than the control group were exposed to 500 mg/kg VPA prenatally to establish an autism model. Intermittent fasting (16:8 time-restricted feeding) and Akkermansia muciniphila (1 × 10⁹ cfu/day) were applied for 30 days. Behavioral tests (stereotypy, social interaction, memory, and anhedonia) were performed during the last eight days of the treatment period, and the rats were sacrificed the following day for collection of brain tissue and serum samples. Proinflammatory, apoptotic, autophagic, and GABAergic markers were measured in the prefrontal cortex and hippocampus, while zonulin levels were measured in the serum. Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test. Results: Prenatal VPA exposure worsened all behavioral and molecular parameters. All treatments improved stereotypy, social interaction, and memory, whereas anhedonia improved only in the combined treatment group. The treatments also decreased neuroinflammation and apoptosis-related imbalance while enhancing autophagy and GABAergic markers. In terms of apoptosis- and autophagy-related markers, the IF-only and probiotic-only treatments were effective in the prefrontal cortex, while the IF + probiotic treatment showed its effect in both brain regions. Lastly, all treatments were successful in alleviating elevated serum zonulin levels. Conclusions: Intermittent fasting and Akkermansia muciniphila alleviate VPA-induced behavioral and neurobiological impairments. The combined treatment, in particular, offers stronger and multi-targeted therapeutic potential.

Background/Objectives: Autism spectrum disorder is a psychological condition characterized by symptoms such as repetitive stereotypic behaviors and social interaction/communication difficulties. It is known that omega-3 deficiency during brain maturation may cause learning disabilities and motor impairment. Therefore, we examined the effects of omega-3 treatment during gestation and/or lactation on autism-related behavioral and molecular deficits in a valproic acid (VPA)-rat model. Methods: Female Wistar rats were divided into five groups: control, VPA (500 mg/kg at G12.5), VPA+omega-3 (gestation), VPA+omega-3 (lactation), and VPA+omega-3 (gestation + lactation). The omega-3 supplement was dissolved in drinking water and offered for consumption daily during gestation and/or lactation. After the treatment period, behavioral tests were performed. The rats were then sacrificed, and inflammatory cytokines, parvalbumin, and glutamate decarboxylase-67 (GAD67) levels in the prefrontal cortex and hippocampus were examined. Results: Prenatal VPA administration increased repetitive behaviors, decreased sociability, impaired memory, and induced anhedonia. The behavioral and neurochemical effects of VPA exposure were more severe in males than in females. Early maternal omega-3 treatments rescued these behavioral changes. The treatments also reversed prenatal VPA-induced neuroinflammation. Lastly, GAD67 and parvalbumin decreases in these brain regions were mitigated by the treatments, the therapeutic effects of which were more pronounced in males. In terms of efficacy, the treatment groups ranked as follows: “gestation + lactation” > “gestation” > “lactation”. Conclusions: Maternal omega-3 supplementation—especially when administered throughout gestation and lactation—provides significant protection against behavioral and neurochemical deficits associated with prenatal VPA exposure. Early omega-3 intake may serve as a valuable complementary strategy in autism intervention.

Fatemeh Jameie, Mehdi Dianatpour, Mahintaj Dara, Zahra Jamali, Nasrin Ghorbani, Gökhan Ünal, Mohammad Saied Salehi, Sareh Pandamooz. Anat Cell Biol -0001;0:. https://doi.org/10.5115/acb.24.213

In this work, the red pigment of Streptomyces sp. A23 strain isolated from Algerian bee pollen was used for the green synthesis of silver nanoparticles (AgNPs) as well as for evaluating their antimicrobial, anticancer and neuroprotective activities. AgNPs were synthesized as a result of the reduction of 1 and 5 mM silver nitrate solutions at various pH values (5, 7 and 9) and were subsequently characterized. AgNPs (5 mM, pH 9) exhibited a maximum UV?Vis absorbance at 433 nm. Dynamic light scattering revealed that the average diameter was 112 nm. A zeta potential peak was found at ?33 mV corresponding to the increased stability. XRD analysis confirmed the crystallization nature of the material. Furthermore, FT-IR analysis revealed the specific functional groups at 3471 to 478 cm-1. In addition, FE-SEM showed that the mean size of the spherical AgNPs was 54.5 nm in diameter. The presence of Ag was revealed by EDX analysis. Additionally, good antimicrobial activity was observed against Enterococcus faecalis ATCC 19433, Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538P, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 7839, with inhibition zones of 32, 30, 30, 27, 25, 20 and 19 mm, respectively. The lowest minimum inhibitory concentration and minimum bactericidal concentration were recorded against B. subtilis ATCC 6633, with a value of 62.5 ?g mL-1. Intriguingly, all the synthesized AgNPs at concentrations of 2, 4 and 8 ?g mL-1 had cytotoxic effects on SHSY5Y neuroblastoma cell lines. In addition, AgNPs (1 mM, pH 7) exhibited the significant neuroprotective activity at the lowest tested concentration. Finally, the AgNPs synthesized using the red pigment of Streptomyces sp. strain A23 can be considered as promising therapeutic agents.

This study aimed to investigate the neuroprotective role of probiotics and 1,25-dyhydroxyvitamin D3 (calcitriol) against neurotoxicity on rotenone-induced human neuroblastoma cell line SH-SY5Y. Rotenone was administered to induce neurotoxic effects in SH-SY5Y cells. Calcitriol and probiotics were administered at different concentrations as pre- and post-treatment. The thiazolyl blue tetrazolium bromide (MTT) assay was performed to measure cell viability. Intracellular protein levels of antioxidant enzymes (protein tyrosine kinase (PTK), superoxide dismutase (SOD), glutathione peroxidase (GSH), glutathione reductase (GSR), and catalase (CAT)) were determined by the enzyme-linked immunosorbent assay (ELISA). Rotenone (150 nM) reduced (p < 0.001) cell viability compared to control cells. Single and combined pretreatments with probiotics (0.01 mg/ml, 0.05 mg/ml, and 0.1 mg/ml) and calcitriol (1.25 M, 2.5 mu M, and 5 mu M) increased (p < 0.05) cell viability compared to rotenone group. In the pre- and post-treatment design, all treatment groups increased the SOD and GSH levels and decreased the GSR levels compared to rotenone. None of the pretreatments reversed the PTK levels (except probiotics: 0.01 mg/ml). Calcitriol (2.5 M) increased the CAT levels in pretreatment design, and probiotics (0.05 mg/ml and 0.1 mg/ml) increased CAT levels in post-treatment design compared to rotenone group. Calcitriol and probiotics protect against rotenone-induced neurotoxicity in SH-SY5Y cells by decreasing reactive oxygen species (ROS) and increasing antioxidant enzyme parameters. These neuroprotective effects of calcitriol and probiotics against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for their potential clinical use in the treatment of Parkinson's disease (PD). [GRAPHICS] .

Objectives: Autism is a devastating neurodevelopmental disorder and recent studies showed that omega-3 or astaxanthin might reduce autistic symptoms due to their anti-inflammatory properties. Therefore, we investigated the effects of omega-3 and astaxanthin on the VPA-induced autism model of rats.Material and Methods : Female Wistar albino pups (n = 40) were grouped as control, autistic, astaxanthin (2 mg/kg), omega-3 (200 mg/kg), and astaxanthin (2 mg/kg)+omega-3 (200 mg/kg). All groups except the control were prenatally exposed to VPA. Astaxanthin and omega-3 were orally administered from the postnatal day 41 to 68 and behavioral tests were performed between day 69 and 73. The rats were decapitated 24 h after the behavioral tests and hippocampal and prefrontal cytokines and 5-HT levels were analyzed by ELISA.Results: VPA rats have increased grooming behavior while decreased sociability (SI), social preference index (SPI), discrimination index (DI), and prepulse inhibition (PPI) compared to control. Additionally, IL-1β, IL-6, TNF-α, and IFN-γ levels increased while IL-10 and 5-HT levels decreased in both brain regions. Astaxanthin treatment raised SI, SPI, DI, PPI, and prefrontal IL-10 levels. It also raised 5-HT levels and decreased IL-6 levels in both brain regions. Omega-3 and astaxanthin + omega-3 increased the SI, SPI, DI, and PPI and decreased grooming behavior. Moreover, they increased IL-10 and 5-HT levels whereas decreased IL-1β, IL-6, TNF-α, IFN-γ levels in both brain regions.Conclusions: Our results showed that VPA administration mimicked the behavioral and molecular changes of autism in rats. Single and combined administration of astaxanthin and omega-3 improved the autistic-like behavioral and molecular changes in the VPA model of rats.