LDH Activity Research Articles

Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line

Oxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant secondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 µM and 100 µM concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content, extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant enzymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed anti-inflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL-6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and anti-inflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing potential as a therapeutic agent in preventing adverse pregnancy outcomes.

Dose-dependent alteration in hepatic and cerebral glucose metabolism following exposure to polystyrene microplastic in Wistar rats

Background: Recently, microplastics (MPs) with dimensions less than 5 mm have gained more attention due to their adverse impact on the environment and living creatures. Polystyrene (PS) particle is a key element of primary microplastics, which are causing numerous health issues such as interruption of energy metabolism, oxidative stress, neurotoxicity, immunotoxicity, digestive gland disorders, reproductive disruption, and genotoxicity in marine living organisms. Method: Alteration in carbohydrate metabolism was evaluated in male Wistar rats (six weeks of age) after four weeks of oral exposure to polystyrene microplastic (PS-MP) at three different doses (0.5mg/L, 5mg/L and 50 mg/L via drinking water). Results: Polystyrene exposure caused a significant decrease in blood glucose, liver glycogen, and pyruvic acid content in liver and cerebral tissue. Free amino nitrogen content significantly altered in the liver and cerebrum in a dose-specific manner. The LDH activity was found to be decreased in the liver, whereas it increased in the cerebral cortex of rats in a dose-responsive fashion. Enzymes like glucose 6-phosphatase, GOT, GPT, and succinate dehydrogenase activities demonstrated differential effects on the liver and cerebrum of rats in terms of energy metabolism. Conclusion: It is suggested that sub-acute polystyrene exposure significantly perturbs glucose metabolism by inducing hypoglycemia associated with decreased glycolysis and increased TCA cycle enzyme function in rat liver in a dose-dependent manner. Gluconeogenesis is also affected differentially by metabolic adjustment in the studied organs.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-β, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-β, and MMP9 gene expression in renal tissues compared to the AlCl3 group. SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.

Mo-doping and construction of the heterostructure between NiFe LDH and NiSx co-trigger the activity enhancement for overall water splitting

To reduce the preparation cost of high-purity hydrogen, it is necessary to search suitable non-precious metal catalysts with high activity and robust stability. Herein, two means (heteroatom-doping and the heterostructure construction) were adopted together to improve the dual-function activity of NiFe LDH which was widely used in water electrolysis. Mo doped NiFe LDH nanoflowers were firstly generated by hydrothermal reaction, and then NiSx was modified on the petals via electrodeposition. Finally, the obtained NF/Mo-NiFe LDH/NiSx with large electrochemical active area exhibits the expected electrochemical performance with the overpotential at 100 mA cm−2 of 169 and 249 mV for hydrogen evolution (HER) and oxygen evolution reaction (OER) respectively. Assembling NF/Mo-NiFe LDH/NiSx into a two-electrode device for the integral water electrolysis, it just requires a cell voltage of 1.69 V to drive a current density of 100 mA cm−2, and keeps stable after 50-hour continuous operation in 1.0 M KOH. Mo-doping not only regulates the electronic structure of the transition metals and reduces the energy barrier of HER intermediates, but also facilitates the generation of reactive sites for OER. Meanwhile, the construction of heterointerface ensures the synergism between NiSx and Mo-NiFe LDH and accelerates the electron transfer across interfaces, thus enhancing the bifunctional performance.

Early B Cell Factor 3 (EBF3) attenuates Parkinson's disease through directly regulating contactin-associated protein-like 4 (CNTNAP4) transcription: An experimental study

Parkinson's disease (PD) is a gradually debilitating neurodegenerative syndrome. Here, we analyzed GSE7621 chip data obtained from the Gene Expression Omnibus (GEO) database to explore the pathogenesis of PD. Early B Cell Factor 3 (EBF3), a member of the highly evolutionarily conserved EBF-transcription factor family, is involved in neuronal development. EBF3 expression is low in the substantia nigra of patients with PD. However, whether EBF3 is implicated in dopaminergic neuron death during PD has not yet been investigated. Therefore, we aimed to reveal the potential anti-apoptotic effect and molecular mechanism of EBF3 in PD. We established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model in vivo and a 1-methyl-4-phenylpyridine (MPP+)-induced SH-SY5Y cell model in vitro. EBF3 was downregulated in the substantia nigra of PD mice and SH-SY5Y cells treated with MPP+, and the m6A methylation modification level was low. Fat mass and obesity-associated protein (FTO) siRNA upregulated m6A methylation modification of EBF3 and extended the EBF3 mRNA half-life. Functionally, as demonstrated by the results of the open-field test, pole test and gait analysis, EBF3 overexpression ameliorated MPTP-induced behavioral disorder. Further, EBF3 overexpression suppressed neuronal apoptosis in vivo, as evidenced by decreased TUNEL+ cells, and the increased activation of caspase-3 and caspase-9. Similar results were obtained in vitro, as reflected by increased cell viability, decreased LDH activity and restored mitochondrial function, collectively protecting SH-SY5Y cells from MPP+-induced apoptosis. Mechanistically, the results of luciferase reporter, ch-IP and DNA pull-down assays confirmed that, as a transcription factor, EBF3 bound to the promoter of CNTNAP4 (a protein associated with neuronal differentiation) and directly regulated CNTNAP4 transcription. Strikingly, CNTNAP4 knockdown markedly abolished the effect of EBF3 on cell apoptosis, thus aggravating PD. In conclusion, the low level of m6A methylation modification may contribute to the low expression of EBF3 during PD. Additionally, EBF3 attenuates PD by activating CNTNAP4 transcription, suggesting that EBF3 may be a novel therapeutic target in PD.

Perioperative treatment of Hirschsprung’s disease in children

The aim of this work: to evaluate the eff ectiveness of the developed methods of perioperative treatment of Hirschsprung’s disease in children. Materials and methods. The study was conducted on the basis of the 2nd SamMI clinic in the period from 2002 to 2022. The obtained data were compared by correlation analysis with clinical and laboratory indices and with changes in solar activity by Wolf’s numbers of the period of child embryogenesis, data of Murmansk Department of HMP). Results. The results of the study of the activity of redox enzymes have established the following. When comparing the enzyme spectrum of the affected intestine and intact muscle, only a difference in the activity of SDH and LDH is revealed. Taking into account the activity of all enzymes in relation to the activity of SDH, it can be noted that alternative energy sources have a greater specific weight in the intestinal mucosa than in the muscle.

Short Road Transport and Slaughter Stress Affects the Expression Profile of Serotonin Receptors, Adrenocortical, and Hematochemical Responses in Horses.

Horse transport is considered a cause of stress in animals and is known to affect the 5-HT concentrations in both the brain and other tissues. The aim of this research was to investigate the effect of horse transportation and slaughter stress on plasma serotonin's concentration and the expression levels of the related 5-HT1B and 5-HT2A receptors in PBMCs. Furthermore, the IL-12 levels and a variety of blood parameters, including triglycerides, total cholesterol, glucose, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, were also considered. This research was carried out on 32 horses submitted to short road transport of 40 km to slaughter. Blood samples were collected in baseline conditions (T0) and 24 h later, after they were slaughtered (T1). The results showed a significantly increased expression of 5-HT1B and 5-HT2A receptors and a significantly decreased expression of IL-12 in PBMCs at T1 vs. T0. Furthermore, a significant increase in cortisol and glucose concentrations, and LDH activity was observed at T1. In contrast, a significantly lower circulating 5-HT concentration was observed at T1 vs. T0. These results indicate that the stress induced by transport and slaughter stimuli led to the serotoninergic system's activation, suggesting that the expression of serotonin receptors could be used as a pivotal marker of stress, with potential applications for the improvement of elective protocols to observe the guidelines relating to transported horses.

Effect and Mechanism of Mycobacterium avium MAV-5183 on Apoptosis of Mouse Ana-1 Macrophages.

To investigate the effects and mechanisms of Mycobacterium avium MAV-5183 protein on apoptosis in mouse Ana-1 macrophages. A pET-21a-MAV-5183 recombinant plasmid was constructed. The recombinant MAV-5183 protein was cloned, expressed, purified, and identified using an anti-His-tagged antibody. Rabbits were immunized to obtain antiserum, and its potency and immunoreactivity were assessed through WB. Mouse Ana-1 macrophages were incubated with varying concentrations of MAV-5183 protein. Flow cytometry, following ANNEXIN V-FITC/PI double staining, detected apoptosis. Western Blot analysis was conducted to identify apoptosis-related molecules Caspase-9/8/3 and vesicle-related molecules ASC, NLRP3, and Cleaved-casp1. ELISA measured TNF-α and IL-6 levels in the culture supernatant. LDH activity and ROS levels were analyzed separately. RT-qPCR measured mRNA levels of Caspase-9/8/3, ASC, NLRP3, Caspase-1, IL-1β, Bax, MAPK-p38, Bcl-2, TNF-α, and IL-6. MAV-5183 protein was successfully cloned, purified, and identified. In in vitro studies on Ana-1 macrophages, MAV-5183 protein increased the expression of Caspase-9/8/3, ASC, NLRP3 (P < 0.01), induced ROS secretion (P < 0.05), and promoted inflammatory cytokine secretion (TNF-α, IL-6, P < 0.0001); however, it did not significantly affect LDH (P > 0.05). MAV-5183 also induced apoptosis in Ana-1 macrophages (P < 0.05). RT-qPCR results indicated a significant increase in mRNA expression of Caspase-9/8/3, ASC, NLRP3, TNF-α, IL-6, MAPK-p38, and pro-apoptotic factor Bax (P < 0.01), with no significant effect on Bcl-2 and IL-1β mRNA (P > 0.05). The data indicate that MAV-5183 induces macrophage apoptosis through a caspase-dependent pathway and promotes inflammatory cytokine secretion via ROS.

Antifibrotic effects of vitamin D3 on human lung fibroblasts derived from patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Up to now, no treatment can stop the progression of IPF. Vitamin D3 (VD) reduces experimental lung fibrosis in murine models and depletion of vitamin D3 might be associated with the reduced survival of patients with IPF. In this context, we determined if VD can prevent the pro-fibrotic functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and control HLFs were derived from surgical lung biopsies collected from patients with IPF or with primary lung cancer, respectively. VD (3-100 nM) markedly reduced the basal and PDGF-induced proliferation of HLFs. VD also altered cell cycle by increasing the percentage of IPF HLFs arrested in the G0/G1 phase, and by downregulating the expression of various cell cycle regulatory proteins. In addition, VD barely prevented the TGF-β1-induced differentiation in HLFs. At 100 nM, VD slightly reduced the expression of the pro-fibrotic marker α-smooth muscle actin, and had no effect on fibronectin and collagen-1 expression. In contrast, 100 nM VD strongly inhibited the aerobic glycolytic metabolism induced by TGF- β1. Finally, VD reduced both the secretion of lactate, the levels of lactate deshydrogenase mRNA and the activity of intracellular LDH in IPF HLFs. In conclusion, our study shows that VD reduced pro-fibrotic functions of HLFs. These findings suggest that it might be interesting to assess the potential clinical benefits of vitamin D supplementation in patients with IPF, especially on lung function decline.

Individual and combined impact of microplastics and lead acetate on the freshwater shrimp (Caridina fossarum): Biochemical effects and physiological responses

Microplastics and heavy metals pollution is recognised as a major problem affecting aquatic ecosystems. For this reason, this study aims to assess the toxicity of different concentrations of polyethylene microplastics (PE-MPs) (0.0, 500, and 1000 μg L−1) with a mean size of 15–25 μm and lead acetate Pb(C2H3O2)2 (0.0, 2.5, and 5 mg L−1), both individually and in combination, through the exposure of the freshwater grass shrimp, Caridinia fossarum for 15 days, focusing on microplastic interaction with co-occurring contaminants. After being exposed to both contaminants, either individually or in combination, significant alterations in numerous biochemical markers were observed. Specifically, exposure to lead acetate alone resulted in significant changes across ALP, AST, ALT, LDH, GGT, and BChE enzyme activity levels indicating hepatotoxicity and neurotoxicity. Also, Pb exposure led to alterations in total antioxidant capacity, MDA, total lipids, and glycogen contents, signalling the onset of oxidative stress. Exposure to PE-MPs alone led to changes in ALP, LDH, GGT, and BChE enzyme levels, and in MDA, total lipids, and glycogen samples' contents. Remarkably, the study observed increased bioaccumulation of lead acetate in samples treated with the combination, emphasizing the synergistic impact of PE-MPs on the toxicity of lead acetate. This synergy was also evident in AST and ALT enzyme activity levels and MDA contents. This underscores the necessity for measures to address both microplastic pollution and heavy metal contamination, taking into account the synergistic behaviour of MPs in the presence of concurrent contaminants.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis

BackgroundThe glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. MethodsPretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. ResultsOMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. ConclusionOur study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Dietary papaya peel extract ameliorates the crowding stress, enhances growth and immunity in Labeo rohita fingerlings.

This study was designed to determine the effects of papaya peel extract (PPE) supplementation on the growth and immunophysiological responses of rohu fingerlings at different stocking densities. In this study, three isonitrogenous (307.2-309.8gkg-1 protein) and isocaloric diets (16.10-16.16MJ digestible energy kg-1) were prepared using three different inclusion levels (0, 5, and 10gkg-1) of PPE. Four hundred and five rohu fingerlings (mean weight: 4.24g ± 0.12) were randomly distributed into nine treatment groups in triplicates viz. low (10nos 75 L-1 or ≈ 0.565kg/m3), medium (15nos 75 L-1 or ≈ 0.848kg/m3), and high (20nos 75 L-1 or ≈ 1.13kg/m3) following a completely randomized design. The study found that increasing stocking density negatively affected fish growth indices, such as weight gain percentage (WG%), feed efficiency ratio (FER), specific growth rate (SGR) and survival. In contrast, dietary PPE supplementation improved growth indices and survival (p < 0.05). We also observed that aminotransferase, lactate (LDH), and malate dehydrogenase (MDH) activity increased with stocking density, whereas 5 and 10gkg-1 PPE supplementation reduced LDH and MDH activity (p < 0.05). PPE supplementation positively affected serum indices, decreased glucose levels, and increased respiratory burst activity (p < 0.05). Interferon-gamma (IFN-γ) expression was highest in the low- and medium-stocking density groups fed with 5gkg-1 PPE, which also increased total immunoglobulin and myeloperoxidase activity while decreasing malondialdehyde concentration (p < 0.05). The results revealed that 5gkg-1 dietary PPE supplementation could be used as a growth promoter and immunostimulant to improve immuno-physiological responses at low and medium stocking densities.

1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis

BackgroundOur previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function by increasing SHP1 expression. We designed this study to further explore the influence of P5C on T cell metabolism, and produced an antibody for targeting P5C to restore the functions of T cells.MethodWe co-immunoprecipated SHP1 from T cells and analyzed the proteins that were bound to it using liquid chromatography mass spectrometry (LC/MS-MS). The influence of P5C on T cells metabolism was also detected by LC/MS-MS. Seahorse XF96 analyzer was further used to identify the effect of P5C on T cells glycolysis. We subsequently designed and produced an antibody for targeting P5C by monoclonal technique and verified its effectiveness to restore the function of T cells in vitro and in vivo.ResultPKM2 and LDHB bind SHP1 in T cells, and P5C could increase the levels of p-PKM2 while having no effect on the levels of PKM2 and LDHB. We further found that P5C influences T cell energy metabolism and carbohydrate metabolism. P5C also inhibits the activity of PKM2 and decreases the content of intracellular lactic acid while increasing the activity of LDH. Using seahorse XF96 analyzer, we confirmed that P5C remarkably inhibits glycolysis in T cells. We produced an antibody for targeting P5C by monoclonal technique and verified that the antibody could oppose the influence of P5C to restore the process of glycolysis and function in T cells. Meanwhile, the antibody also inhibits the growth of prostate tumors in an animal model.ConclusionOur study revealed that P5C inhibits the process of glycolysis in T cells by targeting SHP1/PKM2/LDHB complexes. Moreover, it is important that the antibody for targeting P5C could restore the function of T cells and inhibit the growth of prostate tumors.

Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2).

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.

Pyriproxyfen Contamination in Daphnia magna: Identifying Early Warning Biomarkers.

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, Daphnia magna organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in D. magna exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. Fabd expression was decreased by approximately 20% in exposed daphnids, while vtg expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the hgb1 and hgb2 genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in Daphnia magna during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations.

Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1β, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Eucalyptus torquata seeds: Investigation of phytochemicals profile via LC-MS and its potential cardiopreventive capacity in rats

Due to the side effects of chemical drugs, recent studies have targeted new therapeutic approach using natural bioactive molecules. The purpose of the current study was to explore, for the first time, the cardiopreventive capacity of Eucalyptus torquata seeds extract (ETS) against myocardial infarction induced by Isoproterenol (ISO) in rats. The phytochemical profile was also targeted. The LC-MS/MS analysis revealed the presence of 53 metabolites belonging to hydroxybenzoic acids, lignans, flavonoids, phloroglucinols, oxocins, organic acids, fatty acids, amino acids, and sugars. The in vivo findings showed that ETS supplementation for 28 days significantly attenuated the cardiotoxicity in adult rats by ameliorating the electrocardiographic pattern (ECG), and reducing the activity of LDH, AST, CK-MB, and troponin-T content compared to the infracted group. Furthermore, ETS reduced the cardiac oxidative stress generated by ISO injection via inhibiting lipid peroxidation and ameliorating the activities of enzymatic antioxidants (SOD, and CAT). Additionally, ETS supplementation attenuated the DNA fragmentation and improved the ultrastructural changes in cardiac tissue. The amelioration of the lipid level (TG, TC, LDL-C, and HDL-C), highlighted the antihyperlipidemic action of ETS. The positive effect of the studied extract against ISO-induced cardiac damage could be related to the bioactive compounds, known as effective antioxidant molecules. The current study provides a preliminary pharmacological support for a potential medicinal application of ETS against cardiovascular pathology.

THE CORRELATION PARAMETERS OF CARDIAC DYSFUNCTION ON THE BACKGROUND OF STEATOHEPATOSIS

Introduction. Coronary heart disease (CHD) and its complications in the modern world are one of the main causes of disability and mortality of people of different ages [1-3]. Fatty liver disease - steatohepatosis - is an important factor in the development and progression of CAD and increases the risk of developing type 2 diabetes. On the other hand, information on cardiac dysfunction in patients with coronary heart disease with manifestations of steatohepatosis is insufficient and contradictory, the diagnosis, clinical features and treatment of this pathology are not accurate enough.&#x0D; The aim of the study. Determination of the correlations of the studied indicators in patients with coronary artery disease complicated by fatty liver disease.&#x0D; Research methods. Fatty infiltration of the liver was diagnosed using ultrasound of the abdominal cavity (EUB-6000 scanner; Hitachi Medical Corporation, Japan). The content of NT-proBNP was determined on StatFax-303, the activity of enzymes and indicators of carbohydrate and lipid metabolism were determined using the CRPLX "Roche Diagnostics" reagent set on the COBAS INTEGRA 400 plus automatic analyzer.&#x0D; In order to identify correlations, the coefficient of linear correlation |r| was determined between all studied indicators. The strength of the relationship was estimated by the absolute value of the Pearson linear correlation coefficient, considering that at r &lt;0.25 the relationship is weak, 0.25 &lt;r&lt; 0.75 - a relationship of medium strength, r ˃ 0.75 - correlation the bond is strong. We used the STATISTICA 6.0 software package (StatSoft, USA) [8].&#x0D; Results and discussion. Strong probable positive correlations were found between glucose concentration and the content of triacylglycans, glycated hemoglobin, atherogenicity coefficient, and lipase activity.&#x0D; Strong probable positive correlations were found between the activity of pancreatic amylase and the concentration of creatinine, C-reactive protein, interleukin 1β, NT-proBNP, and ALT activity.&#x0D; Strong probable positive correlations were found between the concentration of NT-proBNP and the content of uric acid, glucose, C-reactive protein, apoprotein A, interleukin 10, LDH activity, and alkaline phosphatase.&#x0D; Strong probable positive correlations were found between the concentration of creatinine and the content of total cholesterol, the content of HDL-cholesterol, LDL-cholesterol, and lipase activity.&#x0D; Strong probable positive correlations were found between the concentration of total cholesterol and the content of HDL-cholesterol, creatinine, and lipase activit&#x0D; Conclusions. Steatohepatosis is a factor in the development and progression of coronary heart disease and probably increases the risk of developing type 2 diabetes. In the group of patients with steatohepatosis, reliable strong correlation links of carbohydrate metabolism with other parameters were revealed. In the group of patients with on the background of steatohepatosis, significant strong correlation of the level of NT-proBNP, cholesterol and creatinine with other parameters was found.

Chemotherapeutic and Antiproliferative Effect of Purified Protein from Marine Catfish Tachysurus Dussumieri on Human Colon Cancer Cell Line.

The present study aimed to investigate the purified protein from the epidermal mucus of marine catfish Tachysurus dussumieri on the human colon cancer cell line. The bioactive protein was purified with the Anion exchange chromatography and the collected fractions were then tested to assess cell viability in HT 29 cells through the MTT assay. The most responding active purified protein fraction (PPF III) was characterized with the MALDI-TOF/MS it shared a similar homology and sequence with 90% of antimicrobial peptides from external secretions of amphibians. Typical morphological changes of apoptotic cells, including cell shrinkage and detachment, DNA damage, and nuclear condensation were observed after the treatment of bioactive protein. PPF III triggered ROS, increasing the LDH activity, disruption of mitochondrial membrane potential, and upregulation of Cleaved caspase 3/9, Cytochrome-c, Bax, and downregulation of Bcl-2 protein and gene expression on HT 29 cells.

Effects of Sophora alopecuroides in a High-Concentrate Diet on the Liver Immunity and Antioxidant Function of Lambs According to Transcriptome Analysis.

The purpose of this study was to determine the effects of Sophora alopecuroides (SA) on liver function, liver inflammatory factor levels, antioxidant indexes and transcriptome in sheep. Twenty-four 3-month-old healthy Dumont hybrid lambs weighing 25.73 ± 2.17 kg were randomly divided into three groups: C1 (the control group), fed a concentrate-to-forage ratio of 50:50; H2 (the high-concentration group), fed a concentrate-to-forage ratio of 70:30; and S3 (the SA group), fed a concentrate-to-forage ratio of 70:30 + 0.1% SA. The results showed that the rumen pH values of the C1 and S3 groups were significant or significantly higher than that of the H2 group (p < 0.05 or p < 0.01). The serum ALT, AST and LDH activities and the LPS and LBP concentrations in the sheep serum and liver in the H2 group were significantly or extremely significantly higher than those in the C1 and S3 groups (p < 0.01), and the IL-10 content and SOD, GPX-PX and T-AOC activities showed the opposite trend (p < 0.05 or p < 0.01). KEGG enrichment analysis showed that the differentially expressed genes were significantly enriched in the ECM-receptor interaction and focal adhesion pathways, which are closely related to immune and antioxidant functions (p-adjust < 0.1). In summary, SA could improve the immune and antioxidant functions of lamb livers under high-concentrate conditions and regulate the mechanism of damage on sheep livers, which is caused by high-concentrate diets and through the expression of related genes in the ECM/FAs pathway.