In vivo Antioxidant Related Effect of Orally Administered Aqueous Extract of Saliva triloba in Human Volunteers

Saliva triloba, belongs to the Lamiaceae family, is one in all the vital medicinal plant species. This work aims to study the antioxidant-related effects of trilobite saliva in the human body through in vivo studies and the effects on liver, kidney, and heart function tests. For five days, nine healthy participants consumed 250 mL of trilobite saliva extract orally. On the fifth day, blood samples were taken one hour before and after the first dosage of water extract (samples I and II, respectively), and again one day after the last dose (ie, day 6, sample III). Before the first dosage, the first blood sample was taken (ie sample I) was used as a control for the subsequent II and III samples. Subsequent determinations were performed: serum total antioxidant status (TAS), red blood cell reduced glutathione (GSH), red blood cell superoxide dismutation (SOD) A activity, malondialdehyde (MDA), and serum-selected biochemical tests. After 5 days of oral administration of trilobite saliva extract in healthy volunteers, serum TAS, erythrocyte GSH and erythrocyte SOD activity were significantly increased, and had no influence on serum biochemical examinations of kidney, liver, heart, pancreas, etc., contrasted with zero-time management. In Conclusion, salivary clover extract has effective anti-oxidation related effects in vivo. Because these findings were obtained in healthy people without oxidative stress, it means that clover saliva will enhance the bottom line of the defense system against probable oxidative stress while having no adverse effects, decreasing or avoiding pathological diseases associated with oxidative stress

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Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-03001-7 ◽

2021 ◽

Author(s):

Shannon L. McArdel ◽

Anne-Sophie Dugast ◽

Maegan E. Hoover ◽

Arjun Bollampalli ◽

Enping Hong ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Blood Cell ◽

Nk Cells ◽

Red Blood Cell ◽

Safety Profile ◽

Nk Cell ◽

Cell Activity ◽

In Vivo Studies

AbstractRecombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15Rα fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an improved safety profile through restricted biodistribution. We assessed the ability of RTX-240 to expand and activate T cells and NK cells and evaluated the in vivo efficacy, pharmacodynamics and tolerability using murine models. Treatment of PBMCs with RTX-240 induced T cell and NK cell activation and proliferation. In vivo studies using mRBC-240, a mouse surrogate for RTX-240, revealed biodistribution predominantly to the red pulp of the spleen, leading to CD8 + T cell and NK cell expansion. mRBC-240 was efficacious in a B16-F10 melanoma model and led to increased NK cell infiltration into the lungs. mRBC-240 significantly inhibited CT26 tumor growth, in association with an increase in tumor-infiltrating proliferating and cytotoxic CD8 + T cells. mRBC-240 was tolerated and showed no evidence of hepatic injury at the highest feasible dose, compared with a 4-1BB agonistic antibody. RTX-240 promotes T cell and NK cell activity in preclinical models and shows efficacy and an improved safety profile. Based on these data, RTX-240 is now being evaluated in a clinical trial.

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Indicator Characterizing Carbonyl-Dependent Modification of Erythrocytic Superoxydismutase as a Biochemical Marker of Oxidative Stress in Coronary Heart Disease

Kardiologiia ◽

10.18087/cardio.2020.5.n1019 ◽

2020 ◽

Vol 60 (5) ◽

pp. 57-61

Author(s):

A. K. Tikhaze ◽

V. Ya. Kosach ◽

V. Z. Lankin ◽

A. A. Panferova ◽

M. D. Smirnova

Keyword(s):

Oxidative Stress ◽

Heart Disease ◽

Stress Intensity ◽

Blood Cell ◽

Red Blood Cell ◽

Oxidative Modification ◽

Oxidative Stress Marker ◽

Control Group ◽

Sod Activity ◽

Stress Marker

Aim To study the oxidative modification of red blood cell Cu,Zn superoxide dismutase (SOD) in patients with ischemic heart disease (IHD) in vivo and in vitro to substantiate the use of a new oxidative stress marker.Material and methods Red blood cell Cu,Zn SOD was measured by depression of nitrotetrazolium blue reduction by the superoxide anion generated in xanthine oxidase xanthine oxidation. Red blood cell Cu,Zn SOD was measured immunochemically. The biochemical study was performed in the control group (patients with low extremity fracture without known history of cardiovascular diseases and hyperlipidemia) and in groups of patients with acute myocardial infarction, stable angina, and decompensated heart failure. For evaluation of oxidative stress intensity in IHD patients, an empirical SOD oxidative modification coefficient (OMCSOD) was proposed, which is a Cu,Zn SOD activity / Cu,Zn SOD content ratio.Results The red blood cell Cu,Zn SOD activity was significantly decreased in all IHD groups compared to the control group. Furthermore, OMCSOD was also considerably decreased in IHD patients, which warrants the use of this biochemical index as an oxidative stress marker.Conclusion It was shown that the Cu,Zn SOD modification was induced by interaction of the enzyme molecules with a natural dicarbonyl, malonic dialdehyde, and OMCSOD can be used for evaluation of oxidative stress intensity in IHD patients.

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The red blood cell as a source for oxidative stress in vivo

Journal of Alzheimer’s Disease & Parkinsonism ◽

10.4172/2161-0460.s1.001 ◽

2013 ◽

Vol 03 (04) ◽

Author(s):

Joseph M. Rifkind

Keyword(s):

Oxidative Stress ◽

Blood Cell ◽

Red Blood Cell

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Beyond just hemoglobin: Red blood cell potentiation of hemoglobin-oxygen unloading in fish

Journal of Applied Physiology ◽

10.1152/japplphysiol.00114.2017 ◽

2017 ◽

Vol 123 (4) ◽

pp. 935-941 ◽

Cited By ~ 3

Author(s):

Colin J. Brauner ◽

Till S. Harter

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Ph Regulation ◽

In Vivo Studies ◽

Heterogeneous Distribution ◽

Disease States ◽

Future Work ◽

Improve Treatment Efficacy

Teleosts comprise 95% of fish species, almost one-half of all vertebrate species, and represent one of the most successful adaptive radiation events among vertebrates. This is thought to be in part because of their unique oxygen (O2) transport system. In salmonids, recent in vitro and in vivo studies indicate that hemoglobin-oxygen (Hb-O2) unloading to tissues may be doubled or even tripled under some conditions without changes in perfusion. This is accomplished through the short circuiting of red blood cell (RBC) pH regulation, resulting in a large arterial-venous pH difference within the RBC and induced reduction in Hb-O2 affinity. This system has three prerequisites: 1) highly pH-sensitive hemoglobin, 2) rapid RBC pH regulation, and 3) a heterogeneous distribution of plasma-accessible CA in the cardiovascular system (presence in the tissues and absence at the gills). Although data are limited, these attributes may be general characteristics of teleosts. Although this system is not likely operational to the same degree in other vertebrates, some of these prerequisites do exist, and the generation and elimination of pH disequilibrium states at the RBC will likely enhance Hb-O2 unloading to some degree. In human disease states, there are conditions that may partly satisfy those for enhanced Hb-O2 unloading, tentatively an avenue for future work that may improve treatment efficacy.

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Pathological mechanism of hidden blood loss after TKA: oxidative stress induced by free fatty acids

10.21203/rs.3.rs-19898/v1 ◽

2020 ◽

Author(s):

Tao Yuan ◽

Xin Yu ◽

Hong Qian ◽

Jia Meng ◽

Hui Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Loss ◽

Blood Cell ◽

Red Blood Cell ◽

Morphological Changes ◽

Sod Activity ◽

Blood Samples ◽

Hidden Blood Loss ◽

Pathological Mechanism ◽

Total Knee

Abstract Objective: To study the correlation between high-level free fat acids（FFA）and red blood cell (RBC) injury and to explore the pathological mechanism of hidden blood loss (HBL) after total knee arthroplasty (TKA).Methods: Perioperative blood indexes were tested in 120 patients underwent unilateral total knee replacement for end-stage knee osteoarthritis. Venous blood samples were collected before operation and 24h, 48h, 72h and 120 h after operations. The changes of FFA, hemoglobin (Hb) and red blood cell number in the blood samples were detected by automatic hematology analyzer. The activity of glutathion peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and hydrogen peroxide (H2O2) levels in the blood were measured. Measurement of reactive oxygen species（ROS）was performed by flow cytometry. Meanwhile, the morphological changes of RBC were analyzed under microscope. Results: Significant hidden blood loss was observed for all patients. The Hb content, RBC and hematocrit（Hct）decreased significantly 24 h after surgery (P <0.05)，while FFA concentration was significantly increased and heteromorphic red blood cells appeared under the microscope. The hemoglobin content decreased to the lowest level at 48 h after the operation (P < 0.01). The change of HBL was the most significant according to the Gross equation with the levels of FFA and ROS in the blood increased significantly and reached the peak at 48 h after operation (P <0.01). Meanwhile, GSH-PX activity, T-SOD activity and H2O2 levels significantly decreased compared with preoperative tested samples (P <0.01). Microscopically, erythrocyte atypia increased significantly with cellular rupture and necrosis identified. After 72 h of operation, ROS concentration began to decline along with FFA concentration. However, the Hb and RBC began to rise. Also, GSH-Px activity, T-SOD activity and H2O2 levels increased as well. All tested parameters tended to return to normal levels five days after surgery.Conclusion: High levels of FFA in blood can induce oxidative stress and damage RBCs, which in turns causes HBL after surgery.

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Effects of Preloading of Stannous Compounds on the Distribution of 99mTc-Pertechnetate

Nuklearmedizin ◽

10.1055/s-0037-1620602 ◽

1977 ◽

Vol 16 (01) ◽

pp. 26-29 ◽

Cited By ~ 1

Author(s):

D. D. Greenberg ◽

P. Som ◽

G. E. Meinken ◽

D. F. Sacker ◽

H. L. Atkins ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Plasma Ratio ◽

99Mtc Pertechnetate ◽

Time Period ◽

Stannous Ion ◽

Distribution Studies

Summary 99mTc-pertechnetate distribution studies were performed in rabbits and mice following pretreatment between 5—336 hours with various routinely used stannous complexes (HSA, MAA, GHT, DTPA, PYPs) containing different amounts of Sn++ (0.17 —15.0 μ mg/kg). Beyond a concentration of 0.26 mg/kg of Sn++ an alteration in 99mTc-pertechnetate distribution was observed. The red blood cell was found to be the most prominent target. An in-vivo reduction of 99mTc-pertechnetate apparently occurred by the presence of stannous ion within the red blood cell. Preloading time period between 5—24 hours did not alter the uptake of RBC/plasma ratio. Beyond that period it decreased slowly and still persisted up to 2 weeks following pretreatment. RBC/ plasma ratio of 99mTcO4 - increased with increased Sn++ content of various commercially available pharmaceutical kits.

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High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS

Molecules ◽

10.3390/molecules26133977 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3977

Author(s):

Shaoyun Wang ◽

Xiaozhu Sun ◽

Shuo An ◽

Fang Sang ◽

Yunli Zhao ◽

...

Keyword(s):

High Performance ◽

Chemical Constituents ◽

Water Extract ◽

Ethanol Extract ◽

In Vivo Studies ◽

Polygonum Multiflorum ◽

Q Exactive ◽

Orbitrap Ms

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

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Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice

Biology ◽

10.3390/biology10010029 ◽

2021 ◽

Vol 10 (1) ◽

pp. 29

Author(s):

Raghubendra Singh Dagur ◽

Moses New-Aaron ◽

Murali Ganesan ◽

Weimin Wang ◽

Svetlana Romanova ◽

...

Keyword(s):

Oxidative Stress ◽

Extracellular Vesicles ◽

Treated Group ◽

Human Hepatocytes ◽

In Vivo Studies ◽

People Living With Hiv ◽

Humanized Mouse Model ◽

And Function

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.

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