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Aim: Schizophrenia involves complex interactions between biological and environmental factors, including childhood trauma, cognitive impairments, and premorbid adjustment. Predicting its severity and progression remains challenging. Biomarkers like glial cell line-derived neurotrophic factor (GDNF) and miRNA-29a may bridge biological and environmental aspects. The goal was to explore the connections between miRNAs and neural proteins and cognitive functioning, childhood trauma, and premorbid adjustment in the first episode of psychosis (FEP)., Method: This study included 19 FEP patients who underwent clinical evaluation with: the Childhood Trauma Questionnaire (CTQ), the Premorbid Adjustment Scale (PAS), the Positive and Negative Syndrome Scale (PANSS), and the Montreal Cognitive Assessment Scale (MoCA). Multiplex assays for plasma proteins were conducted with Luminex xMAP technology. Additionally, miRNA levels were quantitatively determined through RNA extraction, cDNA synthesis, and RT-qPCR on a 7500 Fast Real-Time PCR System., Results: Among miRNAs, only miR-29a-3p exhibited a significant correlation with PAS-C scores (r = -0.513, p = 0.025) and cognitive improvement (r = -0.505, p = 0.033). Among the analyzed proteins, only GDNF showed correlations with MoCA scores at the baseline and after 3 months (r = 0.533, p = 0.0189 and r = 0.598, p = 0.007), cognitive improvement (r = 0.511, p = 0.025), and CTQ subtests. MIF concentrations correlated with the PAS-C subscale (r = -0.5670, p = 0.011)., Conclusion: GDNF and miR-29a-3p are promising as biomarkers for understanding and addressing cognitive deficits in psychosis. This study links miRNA and MIF to premorbid adjustment and reveals GDNF's unique role in connection with childhood trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Szwajca, Kazek, Śmierciak, Mizera, Pomierny-Chamiolo, Szwajca, Biesaga and Pilecki.)

In the text, the synthesis and characteristics of the novel ONS-type vanadium (V) complexes with thioanilide derivatives of amino acids are described. They showed the inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1, and SHP2) in the submicromolar range, as well as the inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxidovanadium(IV) (BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO 4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, including also glucose utilizatiand ONO Complexes are Inhibitors ofon in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

Benzophenone derivatives such as benzophenone-2 (BP-2) belong to the group of endocrine disrupting compounds (EDCs). Increased exposure to EDCs is considered to be an important factor behind the decline of human fertility. The main aim of the present study was to determine the effect of BP-2 on testicular function specified by sperm analysis, the level of sex hormones and their receptors. Since BP-2 has been shown to activate the immune system, another aim of the research was to verify the hypothesis that the immune system may be contributing to the testis toxicity of this compound and for this purpose changes in macrophage and lymphocyte populations in the testes were determined. BP-2 at a dose of 100 mg/kg was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks. It was shown that BP-2 reduced the number and motility of sperm and increased the number of sperm showing morphological changes. By determining the concentration of sex hormones, a significant decrease in testosterone levels and an increase in the blood levels of 17β-estradiol were demonstrated. Similar to the results obtained from the blood samples, testosterone levels in the testes were lowered, which could affect sperm parameters. The effect of BP-2 on lowering testosterone levels and the number of sperm cells may be due to immunoactivation in the testes, because it has been detected that this compound significantly decreased the number of the immunosuppressive resident testicular macrophages (TMs) (CD68 - CD163 + ), but increased pro-inflammatory TMs with monocyte-like properties (CD68+CD163-)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zaneta Broniowska reports financial support was provided by National Science Centre Poland., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and phosphodiesterases (PDEs) 4B/7A activity, we continued our pharmacological studies on 8-alkoxypurine-2,6-diones selected based on previous in vitro screening., Methods: Derivatives 17, 31, and 36 were pharmacologically evaluated in vivo using the formalin test and oxaliplatin-induced neuropathic pain: the von Frey and the cold plate tests, and in the carrageenan-induced edema model. Compound 36, which turned out to be the most promising, was further evaluated in the collagen-induced arthritis model. The pharmacokinetic parameters of this compound were also estimated., Results: All the tested compounds exhibited significant analgesic and anti-inflammatory activities. Compound 36 was additionally characterized by an antiarthritic effect and showed a favorable pharmacokinetic profile in rats., Conclusion: The compounds evaluated in this study represent a new class of derivatives with analgesic and anti-inflammatory activities that involve TRPA1 antagonism and PDE4/7 inhibition., (© 2022. The Author(s).)

The problem of an unbalanced diet, overly rich in fats, affects a significant proportion of the population, including women of childbearing age. Negative metabolic and endocrine outcomes for offspring associated with maternal high-fat diet during pregnancy and/or lactation are well documented in the literature. In this paper, we present our findings on the little-studied effects of this diet on NMDA receptors and cognitive functions in offspring. The subject of the study was the rat offspring born from dams fed a high-fat diet before mating and throughout pregnancy and lactation. Using a novel object location test, spatial memory impairment was detected in adolescent offspring as well as in young adult female offspring. The recognition memory of the adolescent and young adult offspring remained unaltered. We also found multiple alterations in the expression of the NMDA receptor subunits, NMDA receptor-associated scaffolding proteins, and selected microRNAs that regulate the activity of the NMDA receptor in the medial prefrontal cortex and the hippocampus of the offspring. Sex-dependent changes in glutamate levels were identified in extracellular fluid obtained from the medial prefrontal cortex and the hippocampus of the offspring. The obtained results indicate that a maternal high-fat diet during pregnancy and lactation can induce in the offspring memory disturbances accompanied by alterations in NMDA receptor expression., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)