Cure of Mice with Advanced Ovarian Adenocarcinoma CaO1 by the Serum Blood Proteins

The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and fluorescence spectroscopy. The fluorescence emission quenching from the HSA-Trp214 residue and the lifetime data upon RuNTF binding evidenced the formation of a 1:1 {RuNTF-albumin} adduct with log Ksv = (4.58 ± 0.01) and log KB = (4.55 ± 0.01). This is supported by CD data with an induced CD broad band observed at ~450 nm even after short incubation times. Importantly, the binding to either HSA or human apo-transferrin is beneficial to the cytotoxicity of the complex towards human cancer cells by enhancing the cytotoxic activity of RuNTF.

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The Structure and Development of Microbodies in the Fat Body and other Tissues of an Insect (Calpodes Ethlius)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010006773x ◽

1970 ◽

Vol 28 ◽

pp. 148-149

Author(s):

M. Locke ◽

J. T. McMahon

Keyword(s):

Electron Microscopy ◽

Liquid Crystals ◽

Fat Body ◽

Competitive Inhibitor ◽

Dense Core ◽

Urate Oxidase ◽

Blood Proteins ◽

Free Base ◽

The Core ◽

The Matrix

The fat body of insects has always been compared functionally to the liver of vertebrates. Both synthesize and store glycogen and lipid and are concerned with the formation of blood proteins. The comparison becomes even more apt with the discovery of microbodies and the localization of urate oxidase and catalase in insect fat body.The microbodies are oval to spherical bodies about 1μ across with a depression and dense core on one side. The core is made of coiled tubules together with dense material close to the depressed membrane. The tubules may appear loose or densely packed but always intertwined like liquid crystals, never straight as in solid crystals (Fig. 1). When fat body is reacted with diaminobenzidine free base and H2O2 at pH 9.0 to determine the distribution of catalase, electron microscopy shows the enzyme in the matrix of the microbodies (Fig. 2). The reaction is abolished by 3-amino-1, 2, 4-triazole, a competitive inhibitor of catalase. The fat body is the only tissue which consistantly reacts positively for urate oxidase. The reaction product is sharply localized in granules of about the same size and distribution as the microbodies. The reaction is inhibited by 2, 6, 8-trichloropurine, a competitive inhibitor of urate oxidase.

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REPEATED LONG-TERM SPACE FLIGHTS: PROTEOMIC INVESTIGATIONS OF COSMONAUTS' BLOOD

Aerospace and Environmental Medicine ◽

10.21687/0233-528x-2020-54-5-15-22 ◽

2020 ◽

Vol 54 (5) ◽

pp. 15-22

Author(s):

I.M. Larina ◽

◽

D.N. Kashirina ◽

K.S. Kireev ◽

A.I. Grigoriev ◽

...

Keyword(s):

Bone Structure ◽

Space Station ◽

The Body ◽

Coagulation Cascade ◽

Chemical Components ◽

Blood Proteins ◽

Blood Indices ◽

Before And After ◽

Biochemical Indices

We performed the first ever comparative analysis of modifications in the proteome, ionogram and some other blood plasma biochemical indices of 18 male cosmonauts (44 ± 6 years of age) before and after maiden or repeated long-term missions to the Russian segment of the International space station (ISS RS). Levels of proteins, substrates and ions as well as chemical components were measured using the LC-MS-based proteomics and routine biochemical techniques. A total of 256 to 281 indices were investigated with the methods of descriptive statistic, regression analysis, and access to bioinformatics resources. It was shown that blood indices recovery from the maiden and repeated missions reflects changes in the body systems and goes at a various speed. The results of measurements made prior to launch and on day 7 after landing are dependent on the number of missions. The bioinformatics techniques showed that after maiden missions both the mediator proteins of alkaline phosphatase (AP) and blood proteins with reliably changing concentrations are associated with the bio-processes including stress, metabolism and DNA reparation, apoptosis, catabolism and proteolysis. During early re-adaptation from repeated missions the AP level was affected by bone remodeling, phosphorylation, angiogenesis and coagulation cascade suggesting a distinct and urgent trigger of the processes of bone structure and mineralization.

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Photooxidation of blood proteins. VIII. Photooxidation of human haemoglobin in the presence of sensitizers

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19612813 ◽

1961 ◽

Vol 26 (11) ◽

pp. 2813-2816 ◽

Cited By ~ 3

Author(s):

Z. Vodrážka ◽

J. Čejka ◽

J. Salák

Keyword(s):

Blood Proteins ◽

Human Haemoglobin

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A comparison of direct measures of glycaemia and glycated blood proteins in insulin-dependent diabetes mellitus

Clinical Biochemistry ◽

10.1016/s0009-9120(89)80098-0 ◽

1989 ◽

Vol 22 (6) ◽

pp. 457-461 ◽

Cited By ~ 7

Author(s):

Peter H. Winocour ◽

Deepak Bhatnagar ◽

Paramjeet Kalsi ◽

Valerie F. Hillier ◽

David C. Anderson

Keyword(s):

Diabetes Mellitus ◽

Insulin Dependent Diabetes Mellitus ◽

Insulin Dependent Diabetes ◽

Dependent Diabetes Mellitus ◽

Blood Proteins ◽

Insulin Dependent ◽

Direct Measures

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Whole blood and blood components from vertebrates differentially affect egg formation in three species of anautogenous mosquitoes

Parasites & Vectors ◽

10.1186/s13071-021-04594-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Ruby E. Harrison ◽

Mark R. Brown ◽

Michael R. Strand

Keyword(s):

Serum Albumin ◽

Whole Blood ◽

Digestive Enzyme ◽

Vertebrate Host ◽

Cell Protein ◽

Blood Components ◽

Blood Proteins ◽

Serum Albumins ◽

Egg Formation ◽

Reproductive Response

Abstract Background Most female mosquitoes are anautogenous and must blood feed on a vertebrate host to produce eggs. Prior studies show that the number of eggs females lay per clutch correlates with the volume of blood ingested and that protein is the most important macronutrient for egg formation. In contrast, how whole blood, blood fractions and specific blood proteins from different vertebrates affect egg formation is less clear. Since egg formation is best understood in Aedes aegypti, we examined how blood and blood components from different vertebrates affect this species and two others: the malaria vector Anopheles gambiae and arbovirus vector Culex quinquefasciatus. Methods Adult female mosquitoes were fed blood, blood fractions and purified major blood proteins from different vertebrate hosts. Markers of reproductive response including ovary ecdysteroidogenesis, yolk deposition into oocytes and number of mature eggs produced were measured. Results Ae. aegypti, An. gambiae and C. quinquefasciatus responded differently to meals of whole blood, plasma or blood cells from human, rat, chicken and turkey hosts. We observed more similarities between the anthropophiles Ae. aegypti and An. gambiae than the ornithophile C. quinquefasciatus. Focusing on Ae. aegypti, the major plasma-derived proteins (serum albumin, fibrinogen and globulins) differentially stimulated egg formation as a function of vertebrate host source. The major blood cell protein, hemoglobin, stimulated yolk deposition when from pigs but not humans, cows or sheep. Serum albumins from different vertebrates also variably affected egg formation. Bovine serum albumin (BSA) stimulated ovary ecdysteroidogenesis, but more weakly induced digestive enzyme activities than whole blood. In contrast, BSA-derived peptides and free amino acids had no stimulatory effects on ecdysteroidogenesis or yolk deposition into oocytes. Conclusions Whole blood, blood fractions and specific blood proteins supported egg formation in three species of anautogenous mosquitoes but specific responses varied with the vertebrate source of the blood components tested.

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Pt(II)-Thiocarbohydrazone Complex as Cytotoxic Agent and Apoptosis Inducer in Caov-3 and HT-29 Cells through the P53 and Caspase-8 Pathways

Pharmaceuticals ◽

10.3390/ph14060509 ◽

2021 ◽

Vol 14 (6) ◽

pp. 509

Author(s):

Abeer A. Ibrahim ◽

Mohanad M. Kareem ◽

Taghreed H. Al-Noor ◽

Tahani Al-Muhimeed ◽

Abeer A. AlObaid ◽

...

Keyword(s):

Cell Cycle ◽

Immunofluorescence Assay ◽

Cell Cycle Distribution ◽

Caspase 8 ◽

Ovarian Adenocarcinoma ◽

Fragmentation Test ◽

Cycle Arrest ◽

Apoptosis Inducer ◽

Test Flow ◽

Ht 29

In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)-thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by the Pt(II)-thiocarbohydrazone complex was associated with cell cycle arrest at the G0/G1 phase. These findings suggest that the target complex inhibited the proliferation of Caov-3 and HT-29 cells, resulting in the arrest of the cell cycle and induction of apoptosis via the stimulation of the p53 and caspase-8 pathways. The present data suggests that the Pt(II)-thiocarbohydrazone complex could also be a promising chemotherapeutic agent for other types of cancer cells.

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Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

Molecular Psychiatry ◽

10.1038/s41380-021-01197-9 ◽

2021 ◽

Author(s):

Meike Heurich ◽

Melanie Föcking ◽

David Mongan ◽

Gerard Cagney ◽

David R. Cotter

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Specific Protein ◽

First Episode ◽

Clinical High Risk ◽

Blood Proteins ◽

Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

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