Search Results (27)

Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495–0.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32–3.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51–1.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 μmol/L, p = 0.002), ALT (397.0 vs. 213.0 IU/L, p = 0.017), and AST (186.0 vs. 114.4 IU/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases. Full article

Glioblastoma (GBM) is one of the most invasive central nervous system tumors, with rising global incidence. Therapy resistance and poor prognosis highlight the urgent need for new anticancer drugs. Plant alkaloids, a largely unexplored yet promising class of compounds, have previously contributed to oncology treatments. While past reviews provided selective insights, this review aims to collectively compare data from the last decade on (1) plant alkaloid-based anticancer drugs, (2) alkaloid transport across the blood–brain barrier (BBB) in vitro and in vivo, (3) alkaloid mechanisms of action in glioblastoma models (in vitro, in vivo, ex vivo, and in silico), and (4) cytotoxicity and safety profiles. Additionally, innovative drug delivery systems (e.g., nanoparticles and liposomes) are discussed. Focusing on preclinical studies of single plant alkaloids, this review includes 22 botanical families and 28 alkaloids that demonstrated anti-GBM activity. Most alkaloids act in a concentration-dependent manner by (1) reducing glioma cell viability, (2) suppressing proliferation, (3) inhibiting migration and invasion, (4) inducing cell death, (5) downregulating Bcl-2 and key signaling pathways, (6) exhibiting antiangiogenic effects, (7) reducing tumor weight, and (8) improving survival rates. The toxic and adverse effect analysis suggests that alkaloids such as noscapine, lycorine, capsaicin, chelerythrine, caffeine, boldine, and colchicine show favorable therapeutic potential. However, tetrandrine, nitidine, harmine, harmaline, cyclopamine, cocaine, and brucine may pose greater risks than benefits. Piperine’s toxicity and berberine’s poor bioavailability suggest the need for novel drug formulations. Several alkaloids (kukoamine A, cyclovirobuxine D, α-solanine, oxymatrine, rutaecarpine, and evodiamine) require further pharmacological and toxicological evaluation. Overall, while plant alkaloids show promise in glioblastoma therapy, progress in assessing their BBB penetration remains limited. More comprehensive studies integrating glioma research and advanced drug delivery technologies are needed. Full article

(1) Background: The study involves an assessment of the frequency of selected gene variants related to folate uptake and distribution (FOLR1 rs2071010, rs630074, FOLH1 rs61886492, GGH rs11545078, rs3758149 and SLC19A1 rs1051266) in a group of women with fetal demise in the Polish population. (2) Methods: A total of 310 subjects were enrolled in the study. There were 110 females with idiopathic recurrent miscarriages (RM), 80 with stillbirth (IUFD) and 120 healthy controls. Designated SNVs were determined by using PCR-RFLP methods. The difference in fetal demise prevalence was assessed using a chi-square test and logistic regression analysis. (3) Results: The rs630074 variant of the FOLR1 gene is associated with a statistically significant increase in the risk of IUFD in a recessive model (OR = 2.03, 95%CI: 1.06–3.90, p = 0.033). The rs61886492variant f FOLH1 is linked to an increased risk of IUFD in co-dominant (p = 0.030), dominant (OR = 2.62, 95%CI: 1.07–6.38, p = 0.032) and log-additive models (OR = 2.64, 95%CI: 1.15–6.06 p = 0.030). In female carriers of the A allele, the risk of IUFD was 2.8 times higher compared to the control group. No relationship between the mother’s genotype and the newborn’s birth weight or placental weight was observed for the studied SNVs. (4) Conclusions: Our study finds that the rs61886492 variant of the FOLH1 gene is associated with IUFD in Polish women. However, pregnancy failures have a multifactorial pathology and other genetic or environmental factors may also contribute to their complex etiology. Further research, preferably with larger groups of women from different ethnic backgrounds, is needed to confirm the results of the current study. Full article

Background/Objectives: Adaptation can reduce or completely eliminate the effectiveness of antibiotics and antiseptics at clinical concentrations. To our knowledge, no studies have examined fungal adaptation to antiseptics. This study aimed to preliminarily investigate the potential for Candida albicans adaptation to eight antiseptics. Methods: The minimal inhibitory concentration (MIC), drug susceptibility, adaptation to antiseptics, and Karpinski Adaptation Index (KAI) of C. albicans strains were assessed. Results: The antiseptics with the most effective MICs activity against C. albicans were octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHX), and polyhexamethylene biguanide (polyhexanide, PHMB). Sodium hypochlorite (NaOCl) and ethacridine lactate (ET) demonstrated moderate activity, while boric acid (BA), povidone–iodine (PVI), and potassium permanganate (KMnO₄) showed the weakest activity. The MIC values for NaOCl and KMnO₄ were close to or equal to the clinical concentrations used in commercial products. The studied strains were susceptible to econazole, miconazole, and voriconazole. Resistance to other drugs occurred in 10–30% of the strains. Antifungal resistance remained unchanged after antiseptic adaptation testing. The lowest KAI values, indicating very low resistance risk, were observed for CHX, OCT, and PHMB. PVI and BA presented a low risk, ET a moderate risk. KMnO₄ and NaOCl had the highest KAI values, indicating high and very high resistance risk in Candida yeasts. Conclusions: C. albicans strains can adapt to antiseptics to varying extents. For most antiseptics, adaptation does not significantly affect their clinical efficacy. However, due to adaptation, NaOCl and KMnO₄ may become ineffective against C. albicans strains even at clinical concentrations. Full article

Background: Foodborne infections affect approximately 600 million people annually. Simultaneously, many plants contain substances like organic acids, which have antimicrobial activity. The aim of this study was to examine the effects of 21 organic acids, naturally occurring in plants, on four foodborne bacteria (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella enterica Typhimurium) and two fungi (Geotrichum candidum and Penicillium candidum). Methods: The minimal inhibitory concentrations (MIC) of the organic acids against foodborne bacteria and in silico toxicity prediction of acids were investigated. Results: Benzoic and salicylic acids exhibit the best activity against foodborne bacteria (mean MIC < 1 mg/mL). Acetic, chlorogenic, formic, malic, nicotinic, and rosmarinic acids demonstrate slightly weaker activity (mean MICs 1–2 mg/mL). Other acids have moderate or poor activity. The effectiveness of organic acids against foodborne fungi is weaker than against bacteria. Most acids require high concentrations (from 10 to >100 mg/mL) to inhibit fungal growth effectively. The predicted LD50 of organic acids ranges from 48 to 5000 mg/kg. Those potentially safe as food preservatives (MIC < LD50) include ascorbic, chlorogenic, malic, nicotinic, rosmarinic, salicylic, succinic, tannic, and tartaric acids. The studied organic acids are not carcinogenic but many can cause adverse effects such as skin sensitization, eye irritation, and potential nephrotoxicity, hepatotoxicity, or neurotoxicity. Conclusions: Most of the investigated plant-derived organic acids exhibit good antibacterial activity and moderate or poor antifungal effects. Among 21 acids, only 9 appear to be safe as food preservatives (MIC < LD50). The relationship between MIC and LD50 is crucial in determining the suitability of organic acids as food preservatives, ensuring that they are effective against bacteria or fungi at concentrations that are not harmful to humans. Full article

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)—well-studied functional variants involved in one-carbon metabolism—and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49–7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression. Full article

The inappropriate use of antimicrobials, along with environmental conditions, can lead to the emergence of resistant microorganisms. The use of phytopharmaceuticals and herbal medicines has a positive impact and represents a promising alternative. Psidium guajava extracts have been widely reported to have antimicrobial potential; however, studies reporting their activity against resistant bacterial strains are scarce. Because of the emerging resistance, the aim of this study was to analyze the antimicrobial capacity of the aqueous extract of guava leaves against wild-type and resistant bacterial strains. The aqueous extract obtained from the leaves of P. guajava was evaluated by HPLC for the content of total phenolics and tannins, antioxidant activity, and chemical composition. The antimicrobial activity of the extracts was analyzed by the disk diffusion and broth microdilution methods. The results of the chemical analysis of the extracts showed total phenolics content of 17.02 ± 6.87 mg/g of dry extract, total tannin content of 14.09 ± 1.20 mg of tannic acid equivalents/g of dry extract, and moderate antioxidant capacity with an EC₅₀ value of 140 µg/mL. Flavonoids are the major compounds (rutin, hesperidin, and quercetin), followed by phenolic acids. Disk diffusion test results showed the presence of inhibition halos for Gram-positive bacteria (Staphylococcus aureus, sensitive and resistant; Staphylococcus pseudintermedius, sensitive and resistant; and Streptococcus spp., beta-hemolytic), while for Gram-negative bacteria (Escherichia coli, sensitive and resistant), there was no inhibition in the tested concentration range. The Minimal Inhibitory Concentration was 6.8 mg/mL for all Gram-positive strains evaluated. The present study demonstrated the antimicrobial activity of the aqueous extract of P. guajava against sensitive and resistant Gram-positive bacteria. The better antimicrobial activity found in the present study compared with previously reported activity should be highlighted and may be related to the higher concentration of total phenolics present in the tested extract. Moreover, the content of tannins found suggests a species with high quality that produces tannins. These new findings suggest an innovative profile regarding therapeutic resources that can be adopted to combat resistant microbial strains. Full article

Hepatitis C virus (HCV) is a dangerous virus that is responsible for a large number of infections and deaths worldwide. In the treatment of HCV, it is important that the drugs are effective and do not have additional hepatotoxic effects. The aim of this study was to test the in silico activity of 1893 terpenes against the HCV NS5B polymerase (PDB-ID: 3FQK). Two drugs, sofosbuvir and dasabuvir, were used as controls. The GOLD software (CCDC) and InstaDock were used for docking. By using the results obtained from PLP.Fitness (GOLD), pKi, and binding free energy (InstaDock), nine terpenes were finally selected based on their scores. The drug-likeness properties were calculated using Lipinski’s rule of five. The ADMET values were studied using SwissADME and pkCSM servers. Ultimately, it was shown that nine terpenes have better docking results than sofosbuvir and dasabuvir. These were gniditrin, mulberrofuran G, cochlearine A, ingenol dibenzoate, mulberrofuran G, isogemichalcone C, pawhuskin B, 3-cinnamyl-4-oxoretinoic acid, DTXSID501019279, and mezerein. Each docked complex was submitted to 150 ns-long molecular dynamics simulations to ascertain the binding stability. The results show that mulberrofuran G, cochlearine A, and both stereoisomers of pawhuskin B form very stable interactions with the active site region where the reaction product should form and are, therefore, good candidates for use as effective competitive inhibitors. The other compounds identified in the docking screen either afford extremely weak (or even hardly any) binding (such as ingenol dibenzoate, gniditrin, and mezerein) or must first undergo preliminary movements in the active site before attaining their stable binding conformations, in a process which may take from 60 to 80 ns (for DTXSID501019279, 3-cinnamyl-4-oxoretinoic acid or isogemichalcone C). Full article

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 120 healthy controls. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A variant of the kinase insertion domain receptor (KDR) gene (rs2071559) was associated with an increased risk of infertility after adjusting for age and BMI (OR = 0.64; 95% CI: 0.45–0.91, p = 0.013 in a log-additive model). Vascular endothelial growth factor A (VEGFA) rs699947 was associated with an increased risk of recurrent implantation failures under a dominant (OR = 2.34; 95% CI: 1.11–4.94, p_adj. = 0.022) and a log-additive model (OR = 0.65; 95% CI 0.43–0.99, p_adj. = 0.038). Variants of the KDR gene (rs1870377, rs2071559) in the whole group were in linkage equilibrium (D’ = 0.25, r² = 0.025). Gene–gene interaction analysis showed the strongest interactions between the KDR gene SNPs rs2071559–rs1870377 (p = 0.004) and KDR rs1870377–VEGFA rs699947 (p = 0.030). Our study revealed that the KDR gene rs2071559 variant may be associated with infertility and rs699947 VEGFA with an increased risk of recurrent implantation failures in infertile ART treated Polish women. Full article

Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused by viruses such as severe acute respiratory syndrome coronavirus 2, influenza viruses, the parainfluenza virus and rhinoviruses. One of the main challenges in recent years has been severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19. Recently, an increasing number of studies are focusing on the activity of various propolis preparations against SARS-CoV-2 as an adjuvant treatment for this infection. Propolis has shown a few key mechanisms of anti-SARS-CoV-2 action such as: the inhibition of the interaction of the S1 spike protein and ACE-2 protein; decreasing the replication of viruses by diminishing the synthesis of RNA transcripts in cells; decreasing the particles of coronaviruses. The anti-viral effect is observed not only with extracts but also with the single biologically active compounds found in propolis (e.g., apigenin, caffeic acid, chrysin, kaempferol, quercetin). Moreover, propolis is effective in the treatment of hyperglycemia, which increases the risk of SARS-CoV-2 infections. The aim of the literature review was to summarize recent studies from the PubMed database evaluating the antiviral activity of propolis extracts in terms of prevention and the therapy of respiratory tract diseases (in vitro, in vivo, clinical trials). Based upon this review, it was found that in recent years studies have focused mainly on the assessment of the effectiveness of propolis and its chemical components against COVID-19. Propolis exerts wide-spectrum antimicrobial activities; thus, propolis extracts can be an effective option in the prevention and treatment of co-infections associated with diseases of the respiratory tract. Full article

The aim of the study was to investigate the effect of baicalein or Scutellaria baicalensis root extract interaction with methyldopa in pregnant spontaneously hypertensive rats (SHR) at the pharmacodynamic, molecular, and biochemical levels. The rats, after confirming pregnancy, received baicalein (200 mg/kg/day, p.o.) and extract (1000 mg/kg/day, p.o.), in combination with methyldopa (400 mg/kg/day; p.o.), for 14 consecutive days, 1 h before blood pressure and heart rate measurements. In the heart and placenta from mothers after giving birth to their offspring, mRNA expression of factors related to inflammatory processes (TNF-α, Il-1β, IL-6) and vascular diseases (TGF-β, HIF-1α, VEGF, PlGF) was measured. Levels of markers of oxidative stress (superoxide dismutase and malondialdehyde) in the placenta and indicators of myocardial damage (troponin cTnC and cTnI, creatine kinase, myoglobin, and lactate dehydrogenase) in the heart were also assessed. Baicalein co-administered with methyldopa was associated with reduced blood pressure, especially during the first three days. The interactions were more pronounced for such factors as TGF-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, and IL-6. Combined application of baicalein and extract with methyldopa may be of value in the development of a new antihypertensive medication intended for patients suffering from preeclampsia or pregnancy-induced hypertension. Full article

Background: Appropriate levels of cholesterol are necessary for the mother and developing fetus, but theirexcess may cause preeclampsia. The ABCA1 transporter mediates the secretion of cholesterol and is highly regulated at the transcriptional level via the nuclear liver X receptors (LXRs). Methods: Sixteen preeclamptic and 39 normotensives healthy women with uncomplicated pregnancies were involved in the case-control study. The placental levels of ABCA1, LXRA and LXRB mRNA were quantified by real-time quantitative PCR. The concentrations of ABCA1, LXRA and LXRB proteins from the placenta were determined using an enzyme-linked immunosorbent assay Results: We found in the logistic regression model significantly lower placental expression of LXRB mRNA (crude OR = 0.26, 95% CI: 0.07–0.94, p = 0.040) and LXRA protein level (crude OR = 0.19, 95% CI: 0.05–0.69, p = 0.012) in late-onset preeclamptic women compared to healthy pregnant women. The values remained statistically significant after adjustment for possible confounders. Conclusions: Our results suggest that high placenta LXRA mRNA and LXRA protein expression levels decrease the risk of late-onset preeclampsia. These nuclear receptors could play a role in the development of preeclampsia through disturbances of lipid metabolism. Full article

Introduction: Some evidence indicates that the improper trophoblast invasion of maternal spiral arteries could be caused by an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to preeclampsia (PE) development. This study aimed to assess the potential role of MMP1, MMP9, TIMP1 and TIMP2 gene polymorphisms in the pathogenesis of PE. Materials and methods: A total of 308 Polish women, 115 preeclamptic (55 with early-onset preeclampsia [EOPE], 60 with late-onset preeclampsia [LOPE]) and 193 healthy pregnant women, all of Caucasian origin, were recruited to the study. PE was diagnosed following the ACOG criteria. The polymorphic variants of the MMP-TIMP pathway (MMP1 rs1799750, MMP9 rs17576, MMP9 rs17577, TIMP1 rs4898, TIMP2 rs2277698, TIMP2 rs55743137) were genotyped by polymerase chain reaction and restriction fragment length polymorphism. Results: Analyzing all SNPs in the MMP-TIMP pathway, no significant differences in allele frequencies between preeclamptic women and controls were observed. However, comparing the EOPE and LOPE groups with each other, we observed a statistically significant difference between them for the TIMP1 rs4898 variant. In the whole group of 308 women, the mean placenta weight was the lowest in carriers of the rs4898 CC genotype. Post hoc analysis revealed significant differences between CC-CT (p = 0.0209) and CC-TT (p = 0.0469). Additionally, during allele analysis, a statistically significant difference in the mean placenta weight (for C allele 529.32 ± 157.11 g, for T allele 560.24 ± 162.24 g, p = 0.021) was also observed. Conclusion: Our findings suggest a relationship between TIMP1 rs4898 (372T > C) polymorphism and increased risk of early-onset preeclampsia in a population of pregnant Polish women. Our data suggest that the TIMP1 rs4898 C allele might be associated with increased risk for early-onset, but not for late-onset preeclampsia. To evaluate the role of the TIMP1 polymorphic variants in the etiopathology of preeclampsia, further studies with a larger sample size are needed. Full article

Long-term fungal infections that are difficult to treat require new substances for their prevention, treatment, or as adjuvants during antibiotic therapy. Propolis is a very promising source of natural substances that show a wide range of pharmacological properties, including antifungal activity against various fungal strains. The purpose of the literature review was to summarize recent studies (PubMed, Scopus) on progress in evaluating the antifungal activity of chemically defined propolis extracts. During the selection of studies, only those with results of antifungal activity expressed as minimal inhibitory concentration (MIC) and/or minimal fungicidal concentration (MFC) were analyzed. Moreover, plant, animal and environmental factors influencing the chemical composition of propolis are discussed. Mechanisms of antifungal activity of propolis extracts and research trends in the aspect of developing new therapies and the assessment of drug interactions are indicated. The review of the research results shows that there is great progress in the definition of propolis extracts. After comparing the MIC/MFC values, it was assessed that propolis extracts offer a wide range of activity not only against pathogenic Candida strains but also against risky molds; however, the strength of this activity is varied. Full article

Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200–4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10–250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong. Full article