Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases.

This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets.

Vitamins in Gynecologic Malignancies.

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors.

Chemokines play a key role in cancer processes, with CXCL1 being a well-studied example. Due to the lack of a complete summary of CXCL1's role in cancer in the literature, in this study, we examine the significance of CXCL1 in various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi's sarcoma, lung, osteosarcoma, renal, and skin cancers (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma), along with thyroid cancer. We focus on understanding how CXCL1 is involved in the cancer processes of these specific types of tumors. We look at how CXCL1 affects cancer cells, including their proliferation, migration, EMT, and metastasis. We also explore how CXCL1 influences other cells connected to tumors, like promoting angiogenesis, recruiting neutrophils, and affecting immune cell functions. Additionally, we discuss the clinical aspects by exploring how CXCL1 levels relate to cancer staging, lymph node metastasis, patient outcomes, chemoresistance, and radioresistance.

Estrogen α and ß Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.

Glioblastoma multiforme (GBM) is a malignant tumor with a higher prevalence in men and a higher survival rate in transmenopausal women. It exhibits distinct areas influenced by changing environmental conditions. This study examines how these areas differ in the levels of estrogen receptors (ERs) which play an important role in the development and progression of many cancers, and whose expression levels are often correlated with patient survival. This study utilized two research models: an in vitro model employing the U87 cell line and a second model involving tumors resected from patients (including tumor core, enhancing tumor region, and peritumoral area). ER expression was assessed at both gene and protein levels, with the results validated using confocal microscopy and immunohistochemistry. Under hypoxic conditions, the U87 line displayed a decrease in ERß mRNA expression and an increase in ERα mRNA expression. In patient samples, ERß mRNA expression was lower in the tumor core compared to the enhancing tumor region (only in males when the study group was divided by sex). In addition, ERß protein expression was lower in the tumor core than in the peritumoral area (only in women when the study group was divided by sex). Immunohistochemical analysis indicated the highest ERß protein expression in the enhancing tumor area, followed by the peritumoral area, and the lowest in the tumor core. The findings suggest that ER expression may significantly influence the development of GBM, exhibiting variability under the influence of conditions present in different tumor areas.

Could Tumor Necrosis Factor Serve as a Marker for Cardiovascular Risk Factors and Left Ventricular Hypertrophy in Patients with Early-Onset Coronary Artery Disease?

Introduction: Tumor necrosis factor (TNF), a pro-inflammatory cytokine, can be produced by cardiomyocytes, leading to metabolic disorders in the myocardium. The objective of this study was to assess the relationship between plasma levels of the TNF cytokine and the presence of known biochemical and clinical risk factors for cardiovascular disease, along with the parameters of cardiac morphology in patients diagnosed with coronary artery disease (CAD) at a young age. Materials and Methods: The study group included 75 men aged up to 50 years and 25 women aged up to 55 years. The plasma TNF concentration was measured by use of the ELISA assay. Echocardiography and electrocardiographic examinations were performed in all patients. Results: We observed positive correlations for TNF with the BMI ratio, weight, waist and hip circumference. We also found negative correlations for TNF with HDL levels and ApoA concentrations, and positive correlations with the ApoB/ApoA1 ratio, Apo B, IL6, LDL and TG concentrations. These results suggest an association between higher plasma TNF concentrations and components of metabolic syndrome, including dyslipidemia. TNF may be a potential risk factor for impaired diastolic function. Conclusions: While TNF may be useful for diagnosing certain risks in CAD patients, the TNF measurement cannot be used as a surrogate test for echocardiography.

The Role of CXCR1, CXCR2, CXCR3, CXCR5, and CXCR6 Ligands in Molecular Cancer Processes and Clinical Aspects of Acute Myeloid Leukemia (AML).

Acute myeloid leukemia (AML) is a type of leukemia known for its unfavorable prognoses, prompting research efforts to discover new therapeutic targets. One area of investigation involves examining extracellular factors, particularly CXC chemokines. While CXCL12 (SDF-1) and its receptor CXCR4 have been extensively studied, research on other CXC chemokine axes in AML is less developed. This study aims to bridge that gap by providing an overview of the significance of CXC chemokines other than CXCL12 (CXCR1, CXCR2, CXCR3, CXCR5, and CXCR6 ligands and CXCL14 and CXCL17) in AML's oncogenic processes. We explore the roles of all CXC chemokines other than CXCL12, in particular CXCL1 (Gro-α), CXCL8 (IL-8), CXCL10 (IP-10), and CXCL11 (I-TAC) in AML tumor processes, including their impact on AML cell proliferation, bone marrow angiogenesis, interaction with non-leukemic cells like MSCs and osteoblasts, and their clinical relevance. We delve into how they influence prognosis, association with extramedullary AML, induction of chemoresistance, effects on bone marrow microvessel density, and their connection to French-American-British (FAB) classification and FLT3 gene mutations.

Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes.

Human CXCR2 has seven ligands, i.e., CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8/IL-8-chemokines with nearly identical properties. However, no available study has compared the contribution of all CXCR2 ligands to cancer progression. That is why, in this study, we conducted a bioinformatic analysis using the GEPIA, UALCAN, and TIMER2.0 databases to investigate the role of CXCR2 ligands in 31 different types of cancer, including glioblastoma, melanoma, and colon, esophageal, gastric, kidney, liver, lung, ovarian, pancreatic, and prostate cancer. We focused on the differences in the regulation of expression (using the Tfsitescan and miRDB databases) and analyzed mutation types in CXCR2 ligand genes in cancers (using the cBioPortal). The data showed that the effect of CXCR2 ligands on prognosis depends on the type of cancer. CXCR2 ligands were associated with EMT, angiogenesis, recruiting neutrophils to the tumor microenvironment, and the count of M1 macrophages. The regulation of the expression of each CXCR2 ligand was different and, thus, each analyzed chemokine may have a different function in cancer processes. Our findings suggest that each type of cancer has a unique pattern of CXCR2 ligand involvement in cancer progression, with each ligand having a unique regulation of expression.

Assessment of Serum Zn, Cu, Mn, and Fe Concentration in Women with Endometrial Cancer and Different Endometrial Pathologies.

BACKGROUND: There is conflicting evidence on the effect of specific micronutrient concentration and cancer risk. In this study, we investigated the differences in serum zinc, copper, iron, and manganese levels and different endometrial pathologies, including endometrial cancer. METHODS: 110 patients with a confirmed diagnosis of endometrial cancer, benign uterine conditions (endometrial polyp, endometrial hyperplasia, uterine myoma), or normal endometrium were included in the study and assessed in terms of endometrial cancer risk factors. The measurements of serum micronutrients were conducted using inductively coupled plasma optical emission spectrometry. RESULTS: When assessing for differences between serum concentrations of trace metals, we found significant differences in the distribution of Mn (p < 0.001) and Fe (0.034). There was also a significant difference in Cu/Zn ratio between the analyzed groups (p = 0.002). Patients' BMI was found to influence Cu concentration, with obese patients having higher mean copper concentration (p = 0.006). Also, patients' menopausal status was shown to influence Cu concentration with postmenopausal patients having higher Cu levels (p = 0.001). The menopausal status was found to influence Cu/Zn ratio (p = 0.002). Univariable regression analysis did not confirm that any of the micronutrients significantly influence the risk of endometrial cancer. CONCLUSION: The concentration of specific trace metals varies between different histopathological diagnoses of endometrial pathologies. Menopausal status and patient BMI are endometrial cancer risk factors impacted by the concentrations of Cu and Zn and their ratio.

The Clinical Significance and Role of CXCL1 Chemokine in Gastrointestinal Cancers.

One area of cancer research is the interaction between cancer cells and immune cells, in which chemokines play a vital role. Despite this, a comprehensive summary of the involvement of C-X-C motif ligand 1 (CXCL1) chemokine (also known as growth-regulated gene-α (GRO-α), melanoma growth-stimulatory activity (MGSA)) in cancer processes is lacking. To address this gap, this review provides a detailed analysis of CXCL1's role in gastrointestinal cancers, including head and neck cancer, esophageal cancer, gastric cancer, liver cancer (hepatocellular carcinoma (HCC)), cholangiocarcinoma, pancreatic cancer (pancreatic ductal adenocarcinoma), and colorectal cancer (colon cancer and rectal cancer). This paper presents the impact of CXCL1 on various molecular cancer processes, such as cancer cell proliferation, migration, and invasion, lymph node metastasis, angiogenesis, recruitment to the tumor microenvironment, and its effect on immune system cells, such as tumor-associated neutrophils (TAN), regulatory T (Treg) cells, myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, this review discusses the association of CXCL1 with clinical aspects of gastrointestinal cancers, including its correlation with tumor size, cancer grade, tumor-node-metastasis (TNM) stage, and patient prognosis. This paper concludes by exploring CXCL1's potential as a therapeutic target in anticancer therapy.

Preliminary Study of Iron Concentration in the Human Placenta in Twin Pregnancies.

BACKGROUND: Pregnancy significantly increases the demand for iron (Fe) in the female body to facilitate maternal blood volume expansion, placental development, and fetal growth. As Fe flux in pregnancy is significantly influenced by the placenta, the aim of this study was to determine the dependencies between the Fe concentration in the placenta, the infant's morphometric parameters and the woman's morphological blood parameters in the last trimester. METHODS: The study was conducted on 33 women with multiple (dichorionic-diamniotic) pregnancies from whom the placentas were drawn, and their 66 infants, including pairs of monozygotic (n = 23) and mixed-sex twins (n = 10). Fe concentrations were determined based on inductively coupled plasma atomic emission spectroscopy (ICP-OES) using ICAP 7400 Duo, Thermo Scientific. RESULTS: The results of the analysis showed that lower placental Fe concentrations were associated with deteriorated morphometric parameters of infants, including weight and head circumference. Although we found no statistically significant dependencies between Fe concentration in the placenta and the women's morphological blood parameters, higher Fe concentration in the placenta of mothers supplemented with Fe correlated with better morphometric parameters in infants compared to those whose mothers received no Fe supplementation. CONCLUSIONS: The research adds additional knowledge for placental iron-related processes during multiple pregnancies. However, many limitations of the study do not allow detailed conclusions to be assessed, and statistical data should be assessed conservatively.

Reduced Expression of Very-Long-Chain Acyl-CoA Synthetases SLC27A4 and SLC27A6 in the Glioblastoma Tumor Compared to the Peritumoral Area.

This study aimed to analyze solute carrier family 27 (SLC27) in glioblastoma tumors. The investigation of these proteins will provide insight into how and to what extent fatty acids are taken up from the blood in glioblastoma tumors, as well as the subsequent fate of the up-taken fatty acids. Tumor samples were collected from a total of 28 patients and analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). The study also sought to explore the relationship between SLC27 expression and patient characteristics (age, height, weight, body mass index (BMI), and smoking history), as well as the expression levels of enzymes responsible for fatty acid synthesis. The expression of SLC27A4 and SLC27A6 was lower in glioblastoma tumors compared to the peritumoral area. Men had a lower expression of SLC27A5. Notably, a positive correlation was observed between the expression of SLC27A4, SLC27A5, and SLC27A6 and smoking history in women, whereas men exhibited a negative correlation between these SLC27s and BMI. The expression of SLC27A1 and SLC27A3 was positively correlated with the expression of ELOVL6. In comparison to healthy brain tissue, glioblastoma tumors take up fewer fatty acids. The metabolism of fatty acids in glioblastoma is dependent on factors such as obesity and smoking.

Assessment of Cadmium (Cd) and Lead (Pb) Blood Concentration on the Risk of Endometrial Cancer.

BACKGROUND: Cadmium (Cd) and lead (Pb) are heavy metals with carcinogenic potential. Their increased concentration has been correlated with a risk of malignancies, including breast, lung, kidney, gastrointestinal, and gynecological cancers. Most of the studies have evaluated tissue heavy metal concentration. To the best of our knowledge, this is the first study to evaluate blood Cd and lead levels in different uterine pathologies and the risk of endometrial cancer. METHODS: This study included 110 patients with a histopathological diagnosis of endometrial cancer, endometrial polyps, endometrial hyperplasia, uterine myoma, and normal endometrium. The patients included in the study were assessed in terms of their endometrial cancer risk factors and blood heavy metal levels. The analysis was conducted using inductively coupled plasma optical emission spectrometry. RESULTS: There was a significant difference in the Cd and Cd/Pb ratio among the different groups of patients (p = 0.002), with higher a median Cd concentration among the endometrial cancer patients. The differences in Pb concentration were not significant (p = 0.717). There were also no differences in the Cd and Pb concentrations based on the patients' menopausal status nor BMI index. The univariate logistic regression showed a blood cadmium concentration above the median to be associated with an increased risk of endometrial cancer (OR = 5.25; 95% CI 1.56, 17.72). No significant associations were observed between the Pb concentration or Cd/Pb ratio and endometrial cancer risk. CONCLUSION: The concentration of Cd varies in patients diagnosed with different uterine pathologies. Increased blood cadmium concentration seems to be a risk factor for endometrial studies. Further research on greater populations, accounting for environmental and lifestyle heavy metal exposure, is required to validate our findings.

Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis.

One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR).

Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.

C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC chemokine subfamily and a ligand for CXCR2. Its main function in the immune system is the chemoattraction of neutrophils. However, there is a lack of comprehensive reviews summarizing the significance of CXCL1 in cancer processes. To fill this gap, this work describes the clinical significance and participation of CXCL1 in cancer processes in the most important reproductive cancers: breast cancer, cervical cancer, endometrial cancer, ovarian cancer, and prostate cancer. The focus is on both clinical aspects and the significance of CXCL1 in molecular cancer processes. We describe the association of CXCL1 with clinical features of tumors, including prognosis, ER, PR and HER2 status, and TNM stage. We present the molecular contribution of CXCL1 to chemoresistance and radioresistance in selected tumors and its influence on the proliferation, migration, and invasion of tumor cells. Additionally, we present the impact of CXCL1 on the microenvironment of reproductive cancers, including its effect on angiogenesis, recruitment, and function of cancer-associated cells (macrophages, neutrophils, MDSC, and Treg). The article concludes by summarizing the significance of introducing drugs targeting CXCL1. This paper also discusses the significance of ACKR1/DARC in reproductive cancers.

An Assessment of MT1A (rs11076161), MT2A (rs28366003) and MT1L (rs10636) Gene Polymorphisms and MT2 Concentration in Women with Endometrial Pathologies.

Several studies have indicated a relationship between metallothionein (MT) polymorphisms and the development of different pathologies, including neoplastic diseases. However, no studies thus far have been conducted on the influence of MT polymorphisms and the development of endometrial lesions, including endometrial cancer. This study included 140 patients with normal endometrial tissue, endometrial polyps, uterine myomas and endometrial cancer. The tissue MT2 concentration was determined using the ELISA method. MT1A, MT2A and MT1L polymorphisms were analyzed using TaqMan real-time PCR genotyping assays. We found no statistical difference between the tissue MT2 concentration in patients with EC vs. benign endometrium (p = 0.579). However, tissue MT2 concentration was significantly different between uterine fibromas and normal endometrial tissue samples (p = 0.019). Menopause status did not influence the tissue MT2 concentration (p = 0.282). There were no significant associations between the prevalence of MT1A, MT2A and MT1L polymorphisms and MT2 concentration. The age, menopausal status, and diabetes status of patients were identified as EC risk factors.

Synthesis and Significance of Arachidonic Acid, a Substrate for Cyclooxygenases, Lipoxygenases, and Cytochrome P450 Pathways in the Tumorigenesis of Glioblastoma Multiforme, Including a Pan-Cancer Comparative Analysis.

Glioblastoma multiforme (GBM) is one of the most aggressive gliomas. New and more effective therapeutic approaches are being sought based on studies of the various mechanisms of GBM tumorigenesis, including the synthesis and metabolism of arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA). PubMed, GEPIA, and the transcriptomics analysis carried out by Seifert et al. were used in writing this paper. In this paper, we discuss in detail the biosynthesis of this acid in GBM tumors, with a special focus on certain enzymes: fatty acid desaturase (FADS)1, FADS2, and elongation of long-chain fatty acids family member 5 (ELOVL5). We also discuss ARA metabolism, particularly its release from cell membrane phospholipids by phospholipase A2 (cPLA2, iPLA2, and sPLA2) and its processing by cyclooxygenases (COX-1 and COX-2), lipoxygenases (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2), and cytochrome P450. Next, we discuss the significance of lipid mediators synthesized from ARA in GBM cancer processes, including prostaglandins (PGE2, PGD2, and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2)), thromboxane A2 (TxA2), oxo-eicosatetraenoic acids, leukotrienes (LTB4, LTC4, LTD4, and LTE4), lipoxins, and many others. These lipid mediators can increase the proliferation of GBM cancer cells, cause angiogenesis, inhibit the anti-tumor response of the immune system, and be responsible for resistance to treatment.

Calcium, Potassium, Sodium, and Magnesium Concentrations in the Placenta, Umbilical Cord, and Fetal Membrane from Women with Multiple Pregnancies.

Calcium (Ca), potassium (K), sodium (Na), and magnesium (Mg) are the elements responsible for the fundamental metabolic and biochemical processes in the cells of the body. The demand for these elements increases significantly during pregnancy, where an adequate supply protects women from the hypertension common in pre-eclampsia and preterm labor. This study aimed to evaluate the association between macro-elements (Ca, Mg, Na, and K) in the placenta, fetal membrane, and umbilical cord and the morphometric parameters of newborns from multiple pregnancies. The study involved 57 pregnant European women with healthy uncomplicated twin pregnancies (n = 52) and triple pregnancies (n = 5); 40 pairs of dichorionic diamniotic twins, 11 pairs of monochorionic diamniotic twins, 1 pair of monochorionic monoamniotic twins, 3 trichorionic triamniotic triplets, and 2 dichorionic triamniotic triplets. Placentas (n = 107), umbilical cords (n = 114), and fetal membranes (n = 112) were collected immediately following delivery, and then weighed and measured. The levels of Ca, K, Na, and Mg were determined using inductively coupled plasma atomic emission spectroscopy (ICP-OES) in a Thermo Scientific ICAP 7400 Duo (Waltham, MA, USA). The respective mean concentrations of Ca, K, Na, and Mg (mg/kg-1 dry mass) were: 2466, 8873, 9323, and 436 in the placenta; 957, 6173, 26,757, and 326 in the umbilical cord, and 1252, 7460, 13,562, and 370 in the fetal membrane. In the studied materials from northwestern Poland, we found strong positive correlations between Ca and Mg concentrations in both the umbilical cord (r = 0.81, p = 0.00) and the fetal membrane (r = 0.73, p = 0.00); between K and Mg concentrations in the umbilical cord (r = 0.73, p = 0.00); between Ca and K concentrations in the fetal membrane (r = 0.73, p = 0.00), and we found moderately positive correlations between placental Ca concentration and placental weight (ρ = 0.42, p = 0.00) and between umbilical cord Mg concentrations and the length of the pregnancy (ρ = 0.42, p = 0.00). Negative correlations were found between Na and Ca concentrations in the fetal membrane (r = -0.40, p = 0.00) and Na concentrations in the fetal membrane and Mg concentrations in the placenta (r = -0.16, p = 0.02). Negative correlations were confirmed between the length of pregnancy and head circumference (ρ = -0.42; p = 0.00), infant weight (ρ = -0.42; p = 0.00), infant length (ρ = -0.49; p = 0.00), shoulder width (ρ = -0.49; p = 0.00); and between the infant weight and head circumference (ρ = -0.62; p = 0.00), weight before delivery (ρ = -0.36; p = 0.00), infant length (ρ = -0.45; p = 0.00), shoulder width (ρ = -0.63; p = 0.00), and weight gain during pregnancy (ρ = -0.31; p = 0.01). We found statistically significant correlations between cigarette smoking before pregnancy and the women's weight before delivery (ρ = 0.32, p = 0.00), and a negative correlation between the women's ages and infant head circumference (ρ = -0.20, p = 0.02). This is probably the first study to evaluate Ca, Na, K, and Mg concentrations in the afterbirth tissues of multiple pregnancies. It adds to the knowledge of elemental concentrations in multiple pregnancies and their possible effects on fetal morphometric parameters.

Effects of Fermentation Time and Type of Tea on the Content of Micronutrients in Kombucha Fermented Tea.

The fermented tea beverage Kombucha is obtained through a series of biochemical and enzymatic reactions carried out by symbiotic cultures of bacteria and yeasts (SCOBY). It contains organic acids, vitamins, amino acids, and biologically active compounds, notably polyphenols, derived mainly from tea. Kombucha exhibits a range of health-promoting properties, including antioxidant or detoxifying effects. This fermented beverage is traditionally brewed with black tea, but other types of tea are used increasingly, which may have significant implications in terms of chemical composition and health-promoting effects. In this preliminary study, we investigated the content of micronutrients (manganese (Mn), copper (Cu), iron (Fe), chromium (Cr) and zinc (Zn)) by the ICP-OES method in Kombucha prepared with black, red, green and white tea at different time points of fermentation (1, 7, 14 days). It should be noted that the composition of separate ingredients such as tea, leaven or sugar has not been studied. Kombucha had the highest content of zinc-0.36 mg/L to 2.08 mg/L, which accounts for between 3% and 26% of the RDA (Recommended Dietary Allowance) for adults, and the smallest amounts of chromium (0.03 mg/L to 0.09 mg/L), which however represents as much as between 75% and 232% of the RDA. It has been demonstrated that the type of tea as well as the day of fermentation have a significant effect on the concentrations of selected minerals. Kombucha can therefore supplement micronutrients in the human diet.

Response of Skin-Derived and Metastatic Human Malignant Melanoma Cell Lines to Thymoquinone and Thymoquinone-Loaded Liposomes.

Thymoquinone has been proved to be effective against neoplasms, including skin cancer. Its high lipophilicity, however, may limit its potential use as a drug. Melanoma remains the deadliest of all skin cancers worldwide, due to its high heterogeneity, depending on the stage of the disease. Our goal was to compare the anti-cancer activity of free thymoquinone and thymoquinone-loaded liposomes on two melanoma cell lines that originated from different stages of this cancer: skin-derived A375 and metastatic WM9. We evaluated the proapoptotic effects of free thymoquinone by flow cytometry and Western blot, and its mitotoxicity by means of JC-1 assay. Additionally, we compared the cytotoxicity of free thymoquinone and thymoquinone in liposomes by WST-1 assay. Our results revealed a higher antiproliferative effect of TQ in WM9 cells, whereas its higher proapoptotic activity was observed in the A375 cell line. Moreover, the thymoquinone-loaded liposome was proved to exert stronger cytotoxic effect on both cell lines studied than free thymoquinone. Differences in the response of melanoma cells derived from different stages of the disease to thymoquinone, as well as their different responses to free and carrier-delivered thymoquinone, are essential for the development of new anti-melanoma therapies. However, further research is required to fully understand them.

Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.

Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply).