ORCID Profile
0000-0001-8771-998X
Current Organisations
James Cook University
,
Johns Hopkins University
,
Karolinska Institutet
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Publisher: Elsevier BV
Date: 06-2021
Publisher: Informa UK Limited
Date: 09-06-2022
Publisher: Frontiers Media SA
Date: 02-06-2022
Abstract: A high expression level of programmed death-ligand 1 (PD-L1) is observed in different types of cancers (particularly lung cancer). Soluble (s)PD-L1 may be used as a prognostic marker and a target for anti-cancer immunity, as well as, predicting gene therapy or systemic immunotherapy in blocking the PD-1 and PD-L1 checkpoint. Studies that evaluate the effects of the immune regulator selenium on PD-L1 expression show ambiguous results. Thus, we aimed to analyze sPD-L1 levels in s les from patients who underwent different dosages of selenite treatment in phase I clinical trial. We hypothesized that selenite modulates the sPD-L1 levels in the plasma as a consequence of the suggested mode of action of selenotherapy in cancer patients. In conclusion, our results support the view that selenotherapy does not substantially affect the PD-1/PD-L1 axis judged by sPD-L1 analysis. Furthermore, no significant correlation was observed between the survival and sPD-L1 expression nor sPD-L1 changes. However, due to a dynamic in idual sPD-L1 profile and a high variation in survival, we suggest that further studies are needed to identify whether in idual patients can be benefited from combinational seleno- and anti-PD-L1 therapy.
Publisher: MDPI AG
Date: 14-11-2022
DOI: 10.3390/DIAGNOSTICS12112789
Abstract: Critically ill COVID-19 patients with pleural effusion experience longer hospitalization, multisystem inflammatory syndrome, and higher rates of mortality. Generally, pleural effusion can serve as a diagnostic value to differentiate cytokine levels. This study aimed to evaluate the pleural effusions of COVID-19 deceased patients for 182 protein markers. Olink® Inflammation and Organ Damage panels were used to determine the level of 184 protein markers, e.g., ADA, BTC, CA12, CAPG, CD40, CDCP1, CXCL9, ENTPD2, Flt3L, IL-6, IL-8, LRP1, OSM, PD-L1, PTN, STX8, and VEGFA, which were raised significantly in COVID-19 deceased patients, showing over-stimulation of the immune system and ravaging cytokine storm. The rises of DPP6 and EDIL3 also indicate damage caused to arterial and cardiovascular organs. Overall, this study confirms the elevated levels of CA12, CD40, IL-6, IL-8, PD-L1, and VEGFA, proposing their potential either as biomarkers for the severity and prognosis of the disease or as targets for therapy. Particularly, this study reports upregulated ADA, BTC, DPP6, EDIL3, LIF, ENTPD2, Flt3L, and LRP1 in severe COVID-19 patients for the first time. Pearson’s correlation coefficient analysis indicates the involvement of JAK/STAT pathways as a core regulator of hyperinflammation in deceased COVID-19 patients, suggesting the application of JAK inhibitors as a potential efficient treatment.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2018
DOI: 10.1007/S10495-018-1440-4
Abstract: Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge. Circumvention of negative regulators of cell death pathways or development of predictive and response biomarkers is, therefore, quintessential. This review critically discusses the current state of knowledge on targeting negative regulators of cell death signaling pathways including apoptosis, ferroptosis, necroptosis, autophagy, and anoikis and evaluates the recent advances in clinical and preclinical research on biomarkers of negative regulators. It aims to provide a comprehensive platform for designing efficacious polytherapies including novel agents for restoring cell death signaling pathways or targeting alternative resistance pathways to improve the chances for antitumor responses. Overall, it is concluded that nonapoptotic cell death pathways are a potential research arena for drug discovery, development of novel biomarkers and targeted therapies.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JBIOTEC.2016.10.022
Abstract: Human interferon gamma is a cytokine belonging to a erse group of interferons which have a crucial immunological function against mycobacteria and a wide variety of viral infections. To date, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer is an increasing prospect. Recombinant human interferon gamma, as a lucrative biopharmaceutical, has been engineered in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Human interferon gamma is commonly expressed in Escherichia coli, marketed as ACTIMMUNE
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.YEXCR.2017.08.014
Abstract: Human interferon gamma (hIFNγ) affects tumour cells and modulates immune responses, showing promise as an anti-cancer biotherapeutic. This study investigated the effect of glycosylation and expression system of recombinant hIFNγ in ovarian carcinoma cell lines, PEO1 and SKOV3. The efficacy of E. coli- and mammalian-expressed hIFNγ (hIFNγ-CHO and HEK293, glycosylated/de-glycosylated) on cytostasis, cell death (MTT, and Guava-ViaCount
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.BIORTECH.2016.03.041
Abstract: This study investigated hydrolysis approaches for cultivation of the oleaginous red yeast Rhodotorula glutinis for biodiesel production, whilst utilising the residual solids (RS) for biogas production. Macerated fruit and vegetable waste (FVW) (24h-4°C-leachate served as the control, Pcon) was hydrolysed chemically (Chem), thermally (Therm) and using a combined thermo-chemical treatment (T-Chem). All cleared hydrolysates supported growth of R. glutinis, which was nitrogen-limited. T-Chem hydrolysates yielded highest biomass, total fatty acids (TotFA) and RS-derived biogas yields, biomass TotFA failed to meet standards for fuel density and higher heating values, met by the other treatments. Even though Pcon-derived yields were slightly lower, it is recommended for FVW treatment for local biogas and biodiesel production due to energy and environmental impact considerations.
Publisher: Walter de Gruyter GmbH
Date: 09-11-2013
DOI: 10.2478/S11535-013-0248-Z
Abstract: The microalga Porphyridium cruentum (Rhodophyta) has several industrial and pharmaceutical uses, especially for its polysaccharide production. This study aimed to investigate the influence of nitrogen levels as reflected by altered N:P ratios on the production and content of biomass and carbohydrate. N:P molar ratios were altered in batch cultures to range from 1.6 to 50 using the Redfield ratio of 1:16 as reference. Algal growth (estimated as final cell number, biomass concentration and maximum specific growth rate) was negatively affected at low N:P ratios. The optimal N:P ratio for growth was identified at 35–50, with specific growth rates of 0.19 day−1 and maximum cell concentrations of 59·108 cells L−1 and 1.2 g dry weight of biomass L−1. In addition, variation in cell size was seen. Cells with larger diameters were at higher N:P ratios and smaller cells at lower ratios. The cellular carbohydrate content increased under reduced nitrogen availability. However, because accumulation was moderate at the lowest N:P ratio, 0.4 g per g dry weight biomass compared to 0.24 at the Redfield ratio of 16:1, conditions for increased total carbohydrate formation were identified at the N:P ratios optimal for growth. Additionally, carbohydrates were largely accumulated in late exponential to stationary phase.
Publisher: MDPI AG
Date: 20-01-2023
DOI: 10.3390/BIOMEDICINES11020295
Abstract: Cancer is one of the main causes of human death globally and novel chemotherapeutics are desperately required. As a simple selenium oxide, selenite is a very promising chemotherapeutic because of pronounced its dose-dependent tumor-specific cytotoxicity. We previously published a first-in-man systematic phase I clinical trial in patients with cancer (from IV to end-stage) (the SECAR trial) showing that selenite is safe and tolerable with an unexpectable high maximum tolerated dose (MTD) and short half-life. In the present study, we analyzed the selenium species in plasma s les, from the patients participating in the SECAR trial and from various time points and dose cohorts using LC-ICP-MS. In conclusion, selenite, selenosugars, and 1–2 unidentified peaks that did not correspond to any standard, herein denoted ui-selenium, were detected in the plasma. However, trimethylated selenium (trimethylselenonoium) was not detected. The unidentified ui-selenium was eluting close to the selenium-containing amino acids (selenomethionine and selenocysteine) but was not part of a protein fraction. Our data demonstrate that the major metabolite detected was selenosugar. Furthermore, the identification of selenite even long after the administration is remarkable and unexpected. The kinetic analysis did not support that dosing per the body surface area would reduce interin idual variability of the systemic exposure in terms of trough concentrations.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.EJCA.2021.07.013
Abstract: Selenium is an essential trace element for regulating immune functions through redox-regulating activity of selenoproteins (e.g. glutathione peroxidase), protecting immune cells from oxidative stress. However, in cancer, selenium has biological bimodal action depending on the concentration. At nutritional low doses, selenium, depending on its form, may act as an antioxidant, protecting against oxidative stress, supporting cell survival and growth, thus, plays a chemo-preventive role while, at supra-nutritional higher pharmacological doses, selenium acts as pro-oxidant inducing redox signalling and cell death. To date, many studies have been conducted on the benefits of selenium intake in reducing the risk of cancer incidence at the nutritional level, indicating that likely selenium functions as an immunostimulator, i.e. reversing the immunosuppression in tumour microenvironment towards antitumour immunity by activating immune cells (e.g. M
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier
Date: 2022
DOI: 10.1016/BS.MIE.2021.10.019
Abstract: Selenium compounds have pronounced effects on cell growth and proliferation. Nutritional levels induce selenoproteins. However, the antineoplastic effects of supra-nutritional selenium levels are not mediated by selenoproteins. The most studied compound, selenite, was shown in a clinical trial to possess extraordinary pharmacological properties. The uptake of selenite as for GS-Se-SG and selenocystine is dependent on the extracellular reducing environment maintained by the X
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BIOLOGICALS.2016.09.015
Abstract: Human interferon gamma (hIFNγ) is an important cytokine in the innate and adaptive immune system, produced commercially in Escherichia coli. Efficient expression of hIFNγ has been reported once for Pichia pastoris (Wang et al., 2014) - a proven heterologous expression system. This study investigated hIFNγ expression in P. pastoris replicating the previous study and expanding by using four different strains (X33: wild type GS115: HIS
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BIORTECH.2017.06.122
Abstract: The main aim was to integrate FW-recycling with cultivation of Rhodotorula glutinis and anaerobic digestion (AD) for bio-energy and -fuel recovery. Mixed FW was mechanically macerated (Pcon) and hydrolysed (at 250gL
Publisher: Walter de Gruyter GmbH
Date: 12-2015
Abstract: Transcriptional co-regulation of adjacent genes has been observed for prokaryotic and eukaryotic organisms, alike. High levels of gene adjacency were also found in a wide variety of yeast species with a high frequency of co-regulated gene sets. The aim of this research was to study how selective pressure on the Histidinol dehydrogenase gene (HIS4), using amino acid starvation, affects the level of expression and secretion of the adjacent human interferon gamma gene (hIFNγ) in the recombinant Pichia pastoris GS115 strain, a histidine-deficient mutant. hIFNγ was cloned into the pPIC9 vector adjacent to the HIS4 gene, a gene essential for histidine biosynthesis, which was then transformed into P. pastoris. The transformed P. pastoris was cultured under continuous amino acid starvation in amino acid-free minimal medium for ten days, with five inoculations into unspent medium every second day. Under these conditions, only successfully transformed cells (hIFNγ -HIS4 + ) are able to synthesise histidine and therefore thrive. As shown by ELISA, amino acid starvation-induced selective pressure on HIS4 improved expression and secretion of the adjacent hIFNγ by 55% compared to unchallenged cells. RT-qPCR showed that there was also a positive correlation between duration of amino acid starvation and increased levels of the hIFNγ RNA transcripts. According to these results, it is suggested that these adjacent genes (hIFNγ and HIS4) in the transformed P. pastoris are transcriptionally co-regulated and their expression is synchronised. To the best of the knowledge of the authors this is the first study demonstrating that amino acid starvationinduced selective pressure on HIS4 can alter the regulation pattern of adjacent genes in P. pastoris.
No related grants have been discovered for Ali Razaghi.