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Journal of Cardiovascular Pharmacology Apr 2024Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may...
Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP), late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1-50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase (COX) and nitric oxide synthase (NOS). Plasma levels of prothrombin, thrombin-antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid (CSF) levels of TAT were compared via ELISA. Expression of protease-activated receptor (PAR) types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared to NP and LP. TAT was detected in CSF from all groups and significantly elevated in LP (NP: 0.137±0.014 ng/mL, LP: 0.241±0.015 ng/mL, ePE: 0.192±0.028 ng/mL; p<0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of COX or NOS inhibition. PAR1 and PAR2 were found in PAs from all groups co-localized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared to NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.
PubMed: 38922586
DOI: 10.1097/FJC.0000000000001579 -
Journal of Cardiovascular Pharmacology Apr 2024Hyper-catecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of...
Hyper-catecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyper-acute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n=6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (LV, p= 0.021; RV, p=0.021), with upregulation of reactive oxidative species and other pro-fibrosis proteins, after catecholamine infusion alone. After one propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable to sham (LV, p= 0.021; RV, p= 0.043), with additional findings including downregulation of the apoptotic pathway and pro-fibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 MAP kinase pathway, and demonstrates pro-fibrotic changes mediated by matrix metalloproteinase 9, alpha smooth muscle actin, and fibroblast growth factor-23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 MAP kinase pathway, pro-fibrosis, and extrinsic apoptosis pathway.
PubMed: 38922579
DOI: 10.1097/FJC.0000000000001571 -
Biological Trace Element Research Jun 2024The effects of important nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) have been investigated in relation to male...
The effects of important nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) have been investigated in relation to male fertility due to their roles in proper spermatogenesis, sperm maturation, motility, and optimal sperm function. An imbalance between these elements has been associated with several pathologic conditions and male reproductive issues. The purpose of this study was to determine the essential trace and electrolytes elements, such as Ca, Cu, Fe, Mg, Se, and Zn, in human biological samples (blood, serum, and semen) from patients with male infertility. This study used correlational analysis to determine the potential associations between these elements and male fertility. Imbalances in these elements have been linked to various pathological conditions and male reproductive issues. One hundred eighty referent male adults and two hundred twenty-nine patients diagnosed with subtypes of infertility were included in the study, divided into two age groups. Acid digestion was controlled using a microwave oven, and the essential trace elements and electrolytes in the oxidized biological samples were determined using atomic absorption spectrometry. Certified reference materials of blood and serum were used to validate the accuracy of the methodology. The results showed that the concentrations of Ca, Cu, Fe, Mg, Se, and Zn in the blood, serum, and seminal plasma of male adults in all age groups were higher than those in patients with different infertility phenotypes. Essential element deficiency in all biological fluid samples may significantly negatively affect human reproductive health and lead to male infertility. Through a multidimensional approach, our study sought to unravel the intricate biochemical signatures associated with OAT, providing insights that may shape the landscape of diagnostic and therapeutic strategies for male reproductive health.
PubMed: 38922543
DOI: 10.1007/s12011-024-04281-7 -
Inflammopharmacology Jun 2024The endoplasmic reticulum (ER) is an intracellular organelle that contributes to the folding of proteins and calcium homeostasis. Numerous elements can disrupt its... (Review)
Review
The endoplasmic reticulum (ER) is an intracellular organelle that contributes to the folding of proteins and calcium homeostasis. Numerous elements can disrupt its function, leading to the accumulation of proteins that are unfolded or misfolded in the lumen of the ER, a condition that is known as ER stress. This phenomenon can trigger cell death through the activation of apoptosis and inflammation. Glucoraphanin (GRA) is the predominant glucosinolate found in cruciferous vegetables. Various mechanical and biochemical processes activate the enzyme myrosinase, leading to the hydrolysis of glucoraphanin into the bioactive compound sulforaphane. Sulforaphane is an organosulfur compound that belongs to the isothiocyanate group. It possesses a wide range of activities and has shown remarkable potential as an anti-inflammatory, antioxidant, antitumor, and anti-angiogenic substance. Additionally, sulforaphane is resistant to oxidation, has been demonstrated to have low toxicity, and is considered well-tolerable in individuals. These properties make it a valuable natural dietary supplement for research purposes. Sulforaphane has been demonstrated as a potential candidate drug molecule for managing a range of diseases, primarily because of its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, which can be mediated by modulation of ER stress pathways. This review seeks to cover a wealth of data supporting the broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis, through the amelioration of ER stress in both in vivo and in vitro studies.
PubMed: 38922526
DOI: 10.1007/s10787-024-01506-y -
Mikrochimica Acta Jun 2024A ratiometric fluorescence sensing strategy has been developed for the determination of Cu and glyphosate with high sensitivity and specificity based on OPD...
A ratiometric fluorescence sensing strategy has been developed for the determination of Cu and glyphosate with high sensitivity and specificity based on OPD (o-phenylenediamine) and glutathione-stabilized gold nanoclusters (GSH-AuNCs). Water-soluble 1.75-nm size GSH-AuNCs with strong red fluorescence and maximum emission wavelength at 682 nm were synthesized using GSH as the template. OPD was oxidized by Cu, which produced the bright yellow fluorescence oxidation product 2,3-diaminophenazine (DAP) with a maximum fluorescence emission peak at 570 nm. When glyphosate existed in the system, the chelation between glyphosate and Cu hindered the formation of DAP and reduced the fluorescence intensity of the system at the wavelength of 570 nm. Meanwhile, the fluorescence intensity at the wavelength of 682 nm remained basically stable. It exhibited a good linear relationship towards Cu and glyphosate in water in the range 1.0-10 µM and 0.050-3.0 µg/mL with a detection limit of 0.547 µM and 0.0028 µg/mL, respectively. The method was also used for the semi-quantitative determination of Cu and glyphosate in water by fluorescence color changes visually detected by the naked eyes in the range 1.0-10 µM and 0.30-3.0 µg/mL, respectively. The sensing strategy showed higher sensitivity, more obvious color changes, and better disturbance performance, satisfying with the detection demands of Cu and glyphosate in environmental water samples. The study provides a reliable detection strategy in the environment safety fields.
Topics: Glyphosate; Glycine; Copper; Metal Nanoparticles; Phenylenediamines; Gold; Spectrometry, Fluorescence; Limit of Detection; Water Pollutants, Chemical; Colorimetry; Glutathione; Herbicides; Fluorescent Dyes
PubMed: 38922503
DOI: 10.1007/s00604-024-06484-0 -
Nano Convergence Jun 2024Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative,... (Review)
Review
Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative, extracellular vesicles (EVs) derived from stem cells exhibit remarkable abilities to activate critical signaling cascades, thereby facilitating tissue repair. EVs, nano-scale membrane vesicles, mediate intercellular communication by encapsulating a diverse cargo of proteins, lipids, and nucleic acids. Their therapeutic potential lies in delivering cargos, activating signaling pathways, and efficiently mitigating oxidative stress-an essential aspect of overcoming limitations in stem cell-based tissue repair. This review focuses on engineering and applying EVs in tissue regeneration, emphasizing their role in regulating reactive oxygen species (ROS) pathways. Additionally, we explore strategies to enhance EV therapeutic activity, including functionalization and incorporation of antioxidant defense proteins. Understanding these molecular mechanisms is crucial for optimizing EV-based regenerative therapies. Insights into EV and ROS signaling modulation pave the way for targeted and efficient regenerative therapies harnessing the potential of EVs.
PubMed: 38922501
DOI: 10.1186/s40580-024-00430-9 -
Molecular Neurobiology Jun 2024Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of...
Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.
PubMed: 38922486
DOI: 10.1007/s12035-024-04309-y -
Environmental Science and Pollution... Jun 2024The white stork Ciconia ciconia is a bird species located at the top of the trophic pyramid in grassland and wetland ecosystems. This charismatic species is susceptible...
The white stork Ciconia ciconia is a bird species located at the top of the trophic pyramid in grassland and wetland ecosystems. This charismatic species is susceptible to pesticides and their environmental residues. In 2016, we collected blood samples from 114 white stork chicks across Western and Southern Poland. Chicks were sexed by molecular analysis and aged by development pattern. We studied the relationship between the concentration of pesticides (beta-HCH, heptachlor, aldrin, endrin, 4.4'-DDD, 4.4'-DDE and 4.4'-DDT) and of PCB in the chicks' blood with blood morphology and biochemistry parameters in the blood. The mean (± SD) values of concentrations of above detection level pesticides were: for (1) beta-HCH 4.139 ± 19.205; (2) 4.4'-DDE 9.254 ± 91.491 and additionally (3) PCB 16.135 ± 44.777 ppb. We found negative relationships between beta-HCH and oxidative stress enzyme activity in the blood, between beta-HCH and leukocyte concentration and between 4.4'-DDE and catalase activity. We also found a positive relationship between the concentration of pesticides in blood and the age of chicks. Interestingly, we found a higher concentration of PCB in the blood of male stork chicks than in female stork chicks. We provide more evidence that the presence of pesticides in the environment can be a strong stress factor, shaping the health status of birds.
PubMed: 38922474
DOI: 10.1007/s11356-024-34072-5 -
Environmental Science and Pollution... Jun 2024Advanced oxidative processes, such as Photo-Fenton, transform organic contaminants due to the attack by radicals. In this context, the lethal and sub-lethal effects of...
Advanced oxidative processes, such as Photo-Fenton, transform organic contaminants due to the attack by radicals. In this context, the lethal and sub-lethal effects of the Cruiser® 350FS (CRZ) with the active ingredient thiamethoxam (TMX) were investigated using the planarian Girardia tigrina. Degradation of thiamethoxam by the Fenton process was also assessed by using theoretical studies and the efficiency of Solar-Fenton versus Fenton. The 48 h LC value of CRZ for planarians was 478.6 mg L. The regeneration of planarians was significantly affected for concentrations ≥ 17 mg·L of TMX (24 h). The Solar-Fenton showed a high degradation percentage reaching ~70%. The theoretical model showed the atoms of the TMX molecule that will suffer attacks from the formed radicals. Current results open new perspectives concerning the treatment of TMX in the aquatic environment because the 70% degradation seems to be sufficient to reach concentrations that do not induce sub-lethal effects in planarians. Further studies should determine if the by-products generated might be toxic for planaria or other organisms.
PubMed: 38922471
DOI: 10.1007/s11356-024-34067-2 -
Environmental Science and Pollution... Jun 2024Fungicides are pesticides that are frequently used in agriculture because of their action against fungal diseases. However, the widespread application of pesticides...
Fungicides are pesticides that are frequently used in agriculture because of their action against fungal diseases. However, the widespread application of pesticides around the world raises environmental and public health concerns, since these compounds are toxic and can pose risks to ecosystems and human health. The aim of this study was to evaluate the phytotoxic, cytogenotoxic, and biochemical effects of azoxystrobin and carbendazim on Lactuca sativa L. and their physiological effects on Phaseolus vulgaris L. by analyzing the cell cycle and chromosomal and nuclear alterations in L. sativa; the biochemical effects of azoxystrobin and carbendazim on Phaseolus vulgaris L. and their physiological effects on Phaseolus vulgaris L. by analyzing the cell cycle and chromosomal and nuclear alterations in L. sativa; the biochemical effects by analyzing the activity of antioxidant enzymes in L. sativa; and the physiological effects by analyzing chlorophyll content and chlorophyll a fluorescence in P. vulgaris. It was observed that both fungicides were phytotoxic and cytotoxic, reducing root growth and the mitotic index, cytogenotoxic, increasing the occurrence of chromosomal alterations, as well as inducing oxidative stress and an increase in chlorophyll fluorescence emission and altered energy absorption in the plants used as a test system. In view of this, studies such as the one presented here indicate that the use of pesticides, even in small quantities, can lead to damage to the metabolism of plant organisms.
PubMed: 38922465
DOI: 10.1007/s11356-024-34013-2