Inactivation methods for whole influenza vaccine production

Despite tremendous efforts toward vaccination, influenza remains an ongoing global threat. The induction of strain-specific neutralizing antibody responses is a common phenomenon during vaccination with the current inactivated influenza vaccines, so the protective effect of these vaccines is mostly strain-specific. There is an essential need for the development of next-generation vaccines, with a broad range of immunogenicity against antigenically drifted or shifted influenza viruses. Here, we evaluate the potential of whole inactivated vaccines, based on chemical and physical methods, as well as new approaches to generate cross-protective immune responses. We also consider the mechanisms by which some of these vaccines may induce CD8+ T-cells cross-reactivity with different strains of influenza. In this review, we have focused on conventional and novel methods for production of whole inactivated influenza vaccine. As well as chemical modification, using formaldehyde or β-propiolactone and physical manipulation by ultraviolet radiation or gamma-irradiation, novel approaches, including visible ultrashort pulsed laser, and low-energy electron irradiation are discussed. These two latter methods are considered to be attractive approaches to design more sophisticated vaccines, due to their ability to maintain most of the viral antigenic properties during inactivation and potential to produce cross-protective immunity. However, further studies are needed to validate them before they can replace traditional methods for vaccine manufacturing

Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44+ and CD24− breast cancer stem cells

Objectives: Breast cancer stem cells (CSCs) are a small population of tumour cells with the ability of self-renewal and resistance to chemotherapy. Targeting CSCs is a promising strategy for treatment of cancer. A recent study demonstrated that adenosine receptor agonists inhibit glioblastoma CSCs proliferation. At present, the effect of adenosine on breast CSCs has not been reported. Therefore, this study was designed to evaluate the effect of adenosine and its signalling pathways in breast CSCs. Materials and methods: Anti-proliferative effect of adenosine on breast CSCs was evaluated by mammosphere formation and MTS assay. The effect of adenosine on cell cycle progression was examined using flow cytometry. Detection of apoptosis was conducted by Annexin V-FITC. The expression levels of cell cycle and apoptosis regulatory proteins as well as ERK1/2, and GLI-1 were measured by Western blot. Results: Adenosine reduced CSCs population and mammosphere formation in breast CSCs. Adenosine induced G1 cell cycle arrest in breast CSCs in conjunction with a marked down-regulation of cyclin D1 and CDK4. Adenosine also induced apoptosis by regulation of Bax/Bcl-2 ratio, mitochondrial membrane potential depletion and activation of caspase-6. Moreover, adenosine inhibited ERK1/2 phosphorylation and GLI-1 protein expression. Conclusions: These findings indicated that adenosine induces cell cycle arrest and apoptosis through inhibition of GLI-1 and ERK1/2 pathways in breast CSCs. © 2017 John Wiley & Sons Lt

Kopetdaghinanes, pro-apoptotic hemiacetialic cyclomyrsinanes from Euphorbia kopetdaghi

Euphorbia kopetdaghi grows wild in the Northeast parts of Iran. Phytochemical study of its aerial parts led to the isolation of two undescribed cyclomyrsinol macrocyclic diterpenes with a new tetrahydrofuran oxidation pattern containing a hemiacetal group named: kopetdaghinane A and B. The structure of the isolated compounds was elucidated by extensive spectroscopic methods. Cytotoxic activity of kopetdaghinane A was evaluated using standard MTT assay against MCF-7 breast cancer and OVCAR-3 ovary cells. HUVEC cells were used as a normal cell line for calculation of the selectivity index. The MTT showed cyclomyrsinol diterpene has a significant cytotoxic effect with good selectivity indexes against both cell lines but with more selectivity against MCF-7 cells. Apoptosis induction by cyclomyrsinol treatment was confirmed by annexin V�FITC/PI staining, and caspase-6 activation. Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to kopetdaghinane A treatment, while the expression of Bax protein was increased. Moreover, the apoptotic effect of cyclomyrsinol was shown to be related to ROS production, and loss of mitochondrial membrane potential (�Ψm). Taken together, these results showed that kopetdaghinane A inhibits the growth of MCF-7 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may be considered as an investigational compound in breast cancer preclinical study. © 2020 Elsevier B.V

Dietary ginger administration attenuates oxidative stress and immunosuppression caused by oxytetracycline in rainbow trout (Oncorhynchus mykiss)

In the present study, potential ameliorative effects of dietary ginger (GN) were investigated on antioxidant and immune responses of rainbow trout (Oncorhynchus mykiss) during oxytetracycline (OX) administration. As a 2 × 3 factorial design, the fish were orally treated with OX (a daily dose of 100 mg/kg) and GN (either 10 or 20 g/kg diet) for 10 days. Then, blood samples were taken from each treatment to monitor plasma lysozyme, complement (ACH50), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and reduced glutathione (GSH), malondialdehyde (MDA), total immunoglobulin (Ig) and globulin levels. OX treatment significantly decreased SOD (30%), GPx, (10%) and lysozyme (23%) activities, and GSH (19%) levels; however, it increased GST (16%) activity and MDA (28%) levels. Ten grams GN per kg levels significantly decreased SOD (35%), CAT (13%), GST (20%) and MDA (30%), but increased GSH (30%), lysozyme (48%) and globulin (16%). Twenty grams GN per kg diet significantly decreased SOD (26%) and MDA (17%), but increased lysozyme (31%) levels. Interaction effects of dietary GN and OX were observed on plasma MDA and GPx levels, as 10 g GN per kg diet prevented the OTC-induced changes in these parameters. Moreover, 20 g GN per kg diet prevented the OX-induced change in GPx activity and mitigated the MDA elevation by 20%. It is concluded that GN administration at 10 g/kg diet is beneficial in mitigating oxidative stress and immunosuppression of rainbow trout during OX administration. © 2020 John Wiley & Sons Lt

Antimicrobial effects of selenium nanoparticles in combination with photodynamic therapy against Enterococcus faecalis biofilm

Background: Selenium Nanoparticles (SeNPs) were reported as an agent that may enhance the effectiveness of Photodynamic Antimicrobial Chemotherapy (PACT). This in vitro study evaluates the effect of SeNPs on the efficacy of Methylene Blue (MB)-induced PACT against the biofilm formated in 96-well plates and the dentine tubule biofilm of Enterococcus faecalis. Methods: Chitosan coated SeNPs were synthesized using chemical reduction method and were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS). Twenty-four-hour biofilms of E. faecalis were developed on 96-well plates and treated with SeNPs, MB, and Light-Emitting Diode (LED). Also, three-week biofilms of E. faecalis were formed on 67 specimens of dentinal tubules, and the antibacterial effects of MB+SeNPs on these biofilms were studied. Results: The average hydrodynamic diameter of SeNPs was 80/3 nm according to DLS measurement. The combined use of MB and SeNPs significantly reduced Colony-Forming Units (CFUs) of one-day-old E. faecalis biofilms in comparison with the control group (P value < 0.05). Besides, combination therapy had the most antibacterial effect on root canal E. faecalis biofilms at both 200 and 400 µm depths of dentine tubules (P value < 0.001). Of note, about 50 of human fibroblast cells survived at a concentration of 128 µg/ml of SeNPs, compared to the control group. Conclusion: The results demonstrated that the photodynamic therapy modified by SeNPs could be an effective disinfection alternative to the destruction of E. faecalis biofilms and root canal treatment. © 202

The risk factors and laboratory diagnostics for post renal transplant tuberculosis: A case-control, country-wide study on definitive cases

Background. Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients and, because of its infrequency and the lack of medical awareness, it is usually misdiagnosed. This study was carried out to determine frequency and weight of multiple risk factors for post kidney transplantation TB. Methods. A total of 44 cases (0.3), out of 12,820 patients from 12 major kidney transplantation centers in Iran from 1984 to 2003, were compared with 184 healthy transplant subjects who were transplanted by the same surgical team. Results. The mean age of cases and controls was 37.7 (13-63) and 35.6 (8-67) years (P=0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3-168) months in cases and 18.2 (1-180) months in controls (P=0.03). A positive past history of TB was detected in 2 cases and 1 control (P=0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8) and 60 controls (32.6) had rejection before diagnosis of TB (P=0.004; OR=2.7, CI95: 1.3-5.6). Conclusions. To our knowledge, this is the first study that demonstrated an increase in the risk of post-transplant TB by increasing the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes as 2 immunocompromised states. Further study is needed to clarify our new findings, specifically in relation to different immunosuppressive regimens. © 2008 Wiley Periodicals, Inc

Risk factors and laboratory diagnostics for post renal transplant tuberculosis: A case-controlled, country-wide study on definitive cases

Background: Tuberculosis (TB) is a common cause of morbidity and mortality in renal transplant recipients. It is usually misdiagnosed because of lack of medical awareness and its infrequency in renal transplant recipients. Materials and Methods: 44 cases (0.3) with post-transplant TB out of 12820 patients who had renal transplants performed between 1984 to 2003 were found from the hospital records of 12 major kidney transplantation centers in Iran. These cases were compared with 184 healthy transplant subjects whose transplants were performed by the same surgical team as the controls. Results: The mean age of cases and controls was 37.7 (13-63) and 35.6 (8-67) years (p=0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3-168) months in cases and 18.2(1-180) months in controls (p=0.03). A past history of tuberculosis was detected in 2 cases and 1 control (p=0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8) and 60(32.6) controls had rejection prior to diagnosis of TB (p=0.004; OR=2.7, Cl95 1.3-5.6). Conclusion: To our knowledge, this is the first study that demonstrated increasing risk of post-transplant TB by extending the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes. Further study is needed to clarify our new findings specifically in respect of different immunosuppressive regimens. © 2006 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran