Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy.

The impairment of skin integrity derived from derangement of the orthorhombic lateral organization is mainly caused by dysregulation of ceramide amounts in the skin barrier. Ceramides, fatty acids, and cholesterol-containing nano-based formulations have been used to impair the skin barrier. However, there is still a challenge to formulate novel formulations consisting of ceramides due to their chemical structure, poor aqueous solubility, and high molecular weight. In this study, the design and optimization of Ceramide 3 (CER-NP)-loaded liposomes are implemented based on response surface methodology (RSM). The optimum CER-NP-loaded liposome was selected based on its particle size (PS) and polydispersity index (PDI). The optimum CER-NP-loaded liposome was imagined by observing the encapsulation by using a confocal laser scanning microscope (CLSM) within fluorescently labeled CER-NP. The characteristic liquid crystalline phase and lipid chain conformation of CER-NP-loaded liposomes were determined using attenuated total reflectance infrared spectroscopy (ATR-IR). The CER-NP-loaded liposomes were imagined using a field emission scanning electron microscope (FE-SEM). Finally, the in vitro release of CER-NP from liposomes was examined using modified Franz Cells. The experimental and predicted results were well correlated. The CLSM images of optimized liposomes were conformable with the other studies, and the encapsulation efficiency of CER-NP was 93.84 ± 0.87%. ATR-IR analysis supported the characteristics of the CER-NP-loaded liposome. In addition, the lipid chain conformation shows similarity with skin barrier lipid organization. The release pattern of CER-NP liposomes was fitted with the Korsmeyer–Peppas model. The cytotoxicity studies carried out on HaCaT keratinocytes supported the idea that the liposomes for topical administration of CER-NP could be considered relatively safe. In conclusion, the optimized CER-NP-loaded liposomes could have the potential to restore the skin barrier function.

Background/Objectives: Inflammatory bowel diseases primarily encompass Crohn’s disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation in the gastrointestinal tract. The main catabolic pathway of tryptophan is the kynurenine pathway. Our study aims to evaluate serum tryptophan, the kynurenine pathway, and oxidative stress parameters, including total oxidant status and total antioxidant capacity, in patients with Crohn’s disease and ulcerative colitis. Methods: The study included 80 follow-up patients in remission diagnosed with Crohn’s disease and ulcerative colitis who attended the Gastroenterology Outpatient Clinic, as well as 78 healthy controls. Serum tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid levels were measured with liquid chromatography and tandem mass spectrometry (LC-MS/MS). All statistical analysis was performed using R version 4.2.1. Statistical Language. Results: Serum tryptophan, 3-hydroxyanthranilic acid, and total antioxidant capacity were lower in patients with ulcerative colitis and Crohn’s disease compared to those in the control group. The serum total oxidant status in the control group was significantly lower than in patients with Crohn’s disease and ulcerative colitis. Conclusions: The results of our research indicate that tryptophan and kynurenine pathway metabolites could potentially contribute to the pathogenesis of inflammatory bowel diseases.

There are many studies in the literature on thymoquinone (TQ)-related cancer cells and models, and there is no relevant study investigating the efficacy of the oxime derivative of TQ (TQ-Ox). This study synthesized TQ-Ox and examined its cytotoxic, genotoxic and apoptotic properties in ovarian cancer cells. The structure TQ-Ox was confirmed with NMR. The cytotoxicity by luminometric ATP, intracellular reactive oxygen species (iROS) by fluorometric, intracellular calcium (iCa²⁺) by fluorometric, mitochondrial membrane potential (MMP) by flow cytometry, glutathione (GSH) levels with GSH/GSSG-Glo assay, DNA damage by comet assay, and apoptosis by acridine orange/ethidium bromide dye were determined. Concentrations of TQ-Ox were statistically increased cytotoxicity, DNA damage, apoptosis, iROS, and iCa²⁺ in a concentration-dependent manner (p < 0.001). Besides, MMP and GSH levels also decreased statistically significantly (p < 0.001) with increasing concentrations. TQ-Ox would be an effective treatment option by increasing cytotoxicity, genotoxicity, and apoptosis in ovarian carcinoma. Graphical Abstract

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells.