Aleksandra Kupli&#x;ska  Kamila Rz&#x;d  Marek Wojciechowski  S&#x;awomir Milewski  Iwona Gabriel 《International journal of molecular sciences》2022,23(14)

Due to the apparent similarity of fungal and mammalian metabolic pathways, the number of established antifungal targets is low, and the identification of novel ones is highly desirable. The results of our studies, presented in this work, indicate that the fungal biosynthetic pathway of L-methionine, an amino acid essential for humans, seems to be an attractive perspective. The MET2 gene from Candida albicans encoding L-homoserine O-acetyltransferase (CaMet2p), an enzyme catalyzing the first step in that pathway, was cloned and expressed as the native or the oligo-His-tagged fusion protein in Escherichia coli. The recombinant enzymes were purified and characterized for their basic molecular properties and substrate specificities. The purified MET2 gene product revealed the appropriate activity, catalyzed the conversion of L-homoserine (L-Hom) to O-acetyl-L-homoserine (OALH), and exhibited differential sensitivity to several L-Hom or OALH analogues, including penicillamine. Surprisingly, both penicillamine enantiomers (L- and D-Pen) displayed comparable inhibitory effects. The results of the docking of L- and D-Pen to the model of CaMet2p confirmed that both enantiomeric forms of the inhibitor are able to bind to the catalytic site of the enzyme with similar affinities and a similar binding mode. The sensitivity of some fungal cells to L-Pen, depending on the presence or absence of L-Met in the medium, clearly indicate Met2p targeting. Moreover, C. glabrata clinical strains that are resistant to fluconazole displayed a similar susceptibility to L-Pen as the wild-type strains. Our results prove the potential usefulness of Met2p as a molecular target for antifungal chemotherapy.  相似文献   

    

Agata Witczak  Anna Pohory&#x;o  Aleksandra Aftyka  Kamila Pokorska-Niewiada  Grzegorz Witczak 《International journal of molecular sciences》2022,23(21)

Given the importance of breastfeeding infants, the contamination of human milk is a significant public concern. The aim of this study was to assess the contamination of human milk with dioxin-like PCBs (dl-PCBs) and non-dioxin-like PCBs (ndl-PCBs) in relation to the duration of lactation and other influencing factors, especially the frequency of the consumption of selected foods during pregnancy. Based on this, the health risk to infants was assessed and compared to the tolerable daily intake (TDI). PCB determinations were performed using gas chromatography/mass spectrometry. The ∑ndl-PCB content ranged from 0.008 to 0.897 ng/g w.w., at an average of 0.552 ng/g wet weight, which was 55% of the maximum level according to the EU guidelines for foods for infants and young children. The toxic equivalent (TEQ) was in the range of 0.033–5.67 pg-TEQ/g w.w. The content of non-ortho, mono-ortho, and ndl-PCBs in human milk decreased the longer lactation continued. Moreover, when pregnant women smoked tobacco, this correlated significantly with increases in the concentrations of PCB congeners 156, 118, and 189 in human milk. The human milk contents of PCB congeners 77, 81, 186, 118, and 189 were strongly positively correlated with the amount of fish consumed. The content of stable congeners PCB 135 and PCB 153 increased with age.  相似文献   

    

Kamila Kulik  Barbara yy&#x;ska-Granica  Agnieszka Kowalczyk  Przemys&#x;aw Kurowski  Ma&#x;gorzata Gajewska  Magdalena Bujalska-Zadrony 《International journal of molecular sciences》2021,22(24)

The effectiveness of opioids in the treatment of neuropathic pain is limited. It was demonstrated that magnesium ions (Mg²⁺), physiological antagonists of N-methyl-D-aspartate receptor (NMDAR), increase opioid analgesia in chronic pain. Our study aimed to determine the molecular mechanism of this action. Early data indicate the cross-regulation of µ opioid receptor (MOR) and NMDAR in pain control. Morphine acting on MOR stimulates protein kinase C (PKC), while induction of NMDAR recruits protein kinase A (PKA), leading to a disruption of the MOR-NMDAR complex and promoting functional changes in receptors. The mechanical Randall-Selitto test was used to assess the effect of chronic Mg²⁺ and morphine cotreatment on streptozotocin-induced hyperalgesia in Wistar rats. The level of phosphorylated NMDAR NR1 subunit (pNR1) and phosphorylated MOR (pMOR) in the periaqueductal gray matter was determined with the Western blot method. The activity of PKA and PKC was examined by standard enzyme immunoassays. The experiments showed a reduction in hyperalgesia after coadministration of morphine (5 mg/kg intraperitoneally) and Mg²⁺ (40 mg/kg intraperitoneally). Mg²⁺ administered alone significantly decreased the level of pNR1, pMOR, and activity of both tested kinases. The results suggest that blocking NMDAR signaling by Mg²⁺ restores the MOR-NMDAR complex and thus enables morphine analgesia in neuropathic rats.  相似文献   

    

Kamila Buzun  Agnieszka Gornowicz  Roman Lesyk  Krzysztof Bielawski  Anna Bielawska 《International journal of molecular sciences》2021,22(11)

Autophagy is a process of self-degradation that plays an important role in removing damaged proteins, organelles or cellular fragments from the cell. Under stressful conditions such as hypoxia, nutrient deficiency or chemotherapy, this process can also become the strategy for cell survival. Autophagy can be nonselective or selective in removing specific organelles, ribosomes, and protein aggregates, although the complete mechanisms that regulate aspects of selective autophagy are not fully understood. This review summarizes the most recent research into understanding the different types and mechanisms of autophagy. The relationship between apoptosis and autophagy on the level of molecular regulation of the expression of selected proteins such as p53, Bcl-2/Beclin 1, p62, Atg proteins, and caspases was discussed. Intensive studies have revealed a whole range of novel compounds with an anticancer activity that inhibit or activate regulatory pathways involved in autophagy. We focused on the presentation of compounds strongly affecting the autophagy process, with particular emphasis on those that are undergoing clinical and preclinical cancer research. Moreover, the target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented.  相似文献   

    

Krystyna Makowska  Kamila Szyma&#x;ska  Jaros&#x;aw Ca&#x;ka  S&#x;awomir Gonkowski 《International journal of molecular sciences》2021,22(19)

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.  相似文献   

    

Kamila Jaworecka  Joanna Muda-Urban  Marian Rzepko  Adam Reich 《International journal of molecular sciences》2021,22(2)

Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. Approximately, 70–90% of patients with psoriasis suffer from pruritus, an unpleasant sensation that provokes a desire to scratch. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the pathogenesis of psoriasis-related pruritus still remains unclear. In order to improve patients’ quality of life, development of more effective and safer antipruritic therapies is necessary. In turn to make it possible, better understanding of complexed and multifactorial pathogenesis of this symptom is needed. In this article we have systematized the current knowledge about pruritus origin in psoriasis.  相似文献   

    

Kamila Puppel  Beata Kuczyńska 《Journal of the science of food and agriculture》2016,96(13):4321-4328

The term ‘metabolic profile’ refers to the analysis of blood biochemical parameters that are useful to assess and prevent metabolic and nutritional disorders in dairy herds. In the higher standards of milk production, the priority in modern breeding is keeping dairy cows in high lactation and healthy. The proper analysis, as well as control. of their feeding and metabolic status is immensely important for the health condition of the herd. The disproportion between the genetically determined ability for milk production and the limitations in improving the energy value of the ration may be the cause of metabolic disorders. Negative energy balance has a major impact on the body's hormonal balance and organ functions and mostly appears during transition periods: from 3 to 2 weeks prepartum until 2–3 weeks postpartum. The term ‘transition’ is used to underscore the important physiological, metabolic and nutritional changes occurring in this time. The manner in which these changes occur and how they are diagnosed and detected are extremely important, as they are closely related to clinical and subclinical postpartum diseases, lactation and reproductive performance – factors that significantly shape the profitability of production. Therefore the priority for intensive milk production is prevention of metabolic diseases and other disorders. It is the intent of this review to synthesize and summarize the information currently available on metabolic status and physiological changes in the cow's body that occur during lactation, as well as to discuss the interpretation of the results, which will be a useful diagnostic tool in nutritional evaluations of the dairy herd. © 2016 Society of Chemical Industry  相似文献   

    

Agnieszka Piotrowska‐Cyplik  Kamila Myszka  Jakub Czarny  Katarzyna Ratajczak  Ryszard Kowalski  Róża Biegańska‐Marecik  Justyna Staninska‐Pięta  Jacek Nowak  Paweł Cyplik 《Journal of the science of food and agriculture》2017,97(2):659-668

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Kamila Puppel  Ewa Bogusz  Marcin Gołębiewski  Teresa Nałęcz‐Tarwacka  Beata Kuczyńska  Jan Slósarz  Arkadiusz Budziński  Paweł Solarczyk  Małgorzata Kunowska‐Slósarz  Tomasz Przysucha 《Journal of food science》2018,83(1):229-236

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Kamila Gosz  Jzef Haponiuk  Aleksandra Mielewczyk‐Gry&#x;  &#x;ukasz Piszczyk 《Polymer Composites》2019,40(10):3805-3813

In this work, polyurethane/polyisocyanurate (PUR/PIR) foams were modified by two types of expandable graphite (EG) core‐shell composite particles. The pulverized EG core‐shell composite particles were prepared during emulsion polymerization using methyl methacrylate or glycidyl methacrylate for the synthesis of the polymeric shells (poly(methyl methacrylate) (PMMA) and poly(glycidyl methacrylate) (PGMA)), and then the obtained EG_PMMA and EG_PGMA particles were used for a modification of the PUR/PIR foams. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) observations well demonstrated that the EG_PMMA and EG_PGMA particles were successfully synthesized via emulsion polymerization. The foams with different content of EG or EG core‐shell particles were prepared by the single‐step method at NCO/OH ratio equals 2.5. The prepared materials were analyzed in terms of their morphology, flammability, thermal conductivity, and basic physical and mechanical properties. POLYM. COMPOS., 40:3805–3813, 2019. © 2019 Society of Plastics Engineers  相似文献