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Clinicians often rely on selected small molecular compounds from body fluids for the detection, screening or monitoring of numerous life-threatening diseases. Among others, important monoamines – biogenic amines (BAs) – and their metabolites serve as sensitive biomarkers to study the progression or even early detection of on-going brain pathologies or tumors of neuroendocrine origins. Undertaking the task to optimize a reliable method for the simultaneous analysis of the most relevant BAs in biological matrices is of utmost importance for scientists.

Abstract Background Sporulation, characteristic for some bacteria such as Bacillus subtilis, has not been entirely defined yet. Protein phosphatase E (PrpE) and small, acid soluble spore proteins (SASPs) influence this process. Nevertheless, direct result of PrpE interaction on SASPs content in spore coat of B. subtilis has not been evidenced so far. As proteomic approach enables global analysis of occurring proteins, therefore it was chosen in this experiment to compare SASPs occurrence in two strains of B. subtilis, standard 168 and ΔprpE, lacking PrpE phosphatase. Proteomic analysis is still a challenge, and despite of big approach in mass spectrometry (MS) field, the identification reliability remains unsatisfactory. Therefore there is a rising interest in new methods, particularly bioinformatic tools that would harden protein identification. Most of currently applied algorithms are based on MS-data. Information from separation steps is not still in routine usage, even though they also provide valuable facts about analyzed structures. The aim of this research was to apply a model for peptides retention times prediction, based on quantitative structure-retention relationships (QSRR) in SASPs analysis, obtained from two strains of B. subtilis proteome digests after separation and identification of the peptides by LC-ESI-MS/MS. The QSRR approach was applied as the additional constraint in proteomic research verifying results of MS/MS ion search and confirming the correctness of the peptides identifications along with the indication of the potential false positives and false negatives. Results In both strains of B. subtilis, peptides characteristic for SASPs were found, however their identification confidence varied. According to the MS identity parameter Xcorr and difference between predicted and experimental retention times (ΔtR) four groups could be distinguished: correctly and incorrectly identified, potential false positives and false negatives. The ΔprpE strain was characterized by much higher amount of SASPs peptides than standard 168 and their identification confidence was, mostly for alpha- and beta-type SASP, satisfactory. Conclusions The QSRR-based model for predicting retention times of the peptides, was a useful additional to MS tool, enhancing protein identification. Higher content of SASPs in strain lacking PrpE phosphatase suggests that this enzyme may influence their occurrence in the spores, lowering levels of these proteins.

Research over the past years has compared the enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine) of the previously known racemic mixture called ketamine (R/S-ketamine). Esketamine has been found to be more potent, offering three times stronger analgesic effects and 1.5 times greater anesthetic efficacy than arketamine. It provides smoother anesthesia with fewer side effects and is widely used in clinical settings due to its neuroprotective, bronchodilatory, and antiepileptic properties. Approved by the FDA and EMA in 2019, esketamine is currently used alongside SSRIs or SNRIs for treatment-resistant depression (TRD). On the other hand, arketamine has shown potential for treating neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis, offering possible antidepressant effects and anti-inflammatory benefits. While esketamine is already in clinical use, arketamine's future depends on further research to address its safety, efficacy, and optimal dosing. Both enantiomers hold significant clinical value, with esketamine excelling in anesthesia, and arketamine showing promise in neurological and psychiatric treatments. [ABSTRACT FROM AUTHOR]

The discovery of epinephrine (adrenaline) and its subsequent implications in medicine owes significant contributions to Cybulski across different centuries, who, in 1894, was pivotal in identifying the adrenal medulla's role in blood pressure regulation and naming the active substance "nadnerczyna", known today as adrenaline. His work demonstrated the adrenal glands' critical function in the body's regulatory mechanisms beyond the nervous system. Cybulski's groundbreaking research laid foundational knowledge for future endocrinological studies and pharmaceutical advancements. In the late 20th century, Andruszkiewicz collaborated with Silverman at Northwestern University to develop pregabalin, the active ingredient in Lyrica. Their innovative synthesis of gamma-aminobutyric acid derivatives led to a significant advancement in treating epilepsy, neuropathic pain, and fibromyalgia. Andruszkiewicz's expertise in organic chemistry and enzymology was crucial in this collaborative effort, resulting in the successful development and commercialization of Lyrica. Additionally, Mroczkowski's leadership at Pfizer contributed to the development of crizotinib, a notable anaplastic lymphoma kinase and proto-oncogene 1 tyrosine-protein kinase inhibitor used to treat specific types of non-small cell lung cancer. Her work exemplifies the continuing influence of Polish researchers in pioneering drug discovery and advancing therapeutic treatments over the past three centuries. These contributions highlight Poland's significant role in global pharmaceutical innovations and medical research. [ABSTRACT FROM AUTHOR]

Vulvar intraepithelial neoplasia, also known as VIN, is a non-invasive squamous lesion and precursor of squamous cell carcinoma (SCC) of the vulva. There is no screening test for vulvar intraepithelial neoplasia. Diagnosis of VIN is made clinically and confirmed with a biopsy. We describe a 66-year-old woman with a condyloma-like tumour located in the skin on the vestibule of the vagina. A biopsy sample was taken from the nodule. The definitive diagnosis is supported by the histological examination (VIN III) and immunohistochemical examination of p16(+), p53(+), and a few cell nuclei. The case provides information on the importance of multidisciplinary cooperation. Lifelong surveillance is essential since the resection of individual lesions does not guarantee the prevention of invasive cancer. [ABSTRACT FROM AUTHOR]