COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity ...and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2 + mice.
(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic ...examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers.
Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. ...Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72.sup.nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.
Monosodium glutamate (MSG) is found in refined foods. Apocynin (APO) is a selective NADPH oxidase (NOX) inhibitor. The aim of this experimental study was to investigate possible effects of MSG and ...the curative effects of APO in rats. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (Normal control, APO, MSG and MSG + APO, n:7 for each group). The MSG and MSG + APO groups received 120 mg/kg MSG solution orally for 28 consecutive days. The APO and MSG + APO groups received 25 mg/kg APO solution orally for 5 days until the end of the experiment. At the end of the experiment, all rats were sacrificed and liver tissue and blood samples were taken for histological, ultrastructural, and biochemical analyses. In the MSG group, vacuolization and loss in glycogen content in the hepatocytes, leukocyte infiltration and fibrosis in the liver parenchyme and portal triads, were observed. Terminal deoxynucleotidyl transferase dUTP (TUNEL)-positivity and NADPH oxidase (NOX)-2-positivity were higher in the MSG group compared with the other experimental groups. The concentrations of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin, malondialdehyde (MDA), and myeloperoxidase (MPO) were higher, whereas albumin, glutathione (GSH), and superoxide (SOD) levels were lower in the MSG group. All these data has been reversed in MSG + APO group. The histological and biochemical criteria indicated the prominent ameliorating effect of APO on MSG -induced liver injury.
Abstract
The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis ...A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10
13
or 10
14
viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.
the aim of this study was to investigate the effects of apocynin (APO) on hormone levels, the blood-testis barrier, and oxidative biomarkers in monosodium glutamate (MSG) induced testicular ...degeneration.
Sprague Dawley male rats (150-200 g; n = 32) were randomly distributed into four groups: control, APO, MSG, and MSG + APO. MSG and MSG + APO groups were administered MSG (120 mg/kg) for 28 days. Moreover, the APO and MSG + APO groups received APO (25 mg/kg) during the last five days of the experiment. All administrations were via oral gavage. Finally, biochemical analyses were performed based on the determination of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), as well as light and transmission electron microscopic examinations, assessment of sperm parameters, ZO-1, occludin, NOX-2, and TUNEL immunohistochemistry were evaluated.
MSG increased both the oxidative stress level and apoptosis, decreased cell proliferation, and caused degeneration in testis morphology including in the blood-testis barrier. Administration of apocynin reversed all the deteriorated morphological and biochemical parameters in the MSG + APO group.
apocynin is considered to prevent testicular degeneration by maintaining the integrity of the blood-testis barrier with balanced hormone and oxidant/antioxidant levels.
Objective: Relapsed and refractory CD19-positive B-cell acute
lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)
are the focus of studies on hematological cancers. Treatment of
these ...malignancies has undergone recent transformation with the
development of new gene therapy and molecular biology techniques,
which are safer and well-tolerated therapeutic approaches. The CD19
antigen is the most studied therapeutic target in these hematological
cancers. This study reports the results of clinical-grade production,
quality control, and in vivo efficacy processes of ISIKOK-19 cells as the
first academic clinical trial of CAR-T cells targeting CD19-expressing B
cells in relapsed/refractory ALL and NHL patients in Turkey.
Materials and Methods: We used a lentiviral vector encoding the
CD19 antigen-specific antibody head (FMC63) conjugated with the
CD8-CD28-CD3ζ sequence as a chimeric antigen receptor (CAR) along
with a truncated form of EGFR (EGFRt) on human T-lymphocytes
(CAR-T). We preclinically assessed the efficacy and safety of the
manufactured CAR-T cells, namely ISIKOK-19, from both healthy
donors’ and ALL/NHL patients’ peripheral blood mononuclear cells.
Results: We showed significant enhancement of CAR lentivirus
transduction efficacy in T-cells using BX-795, an inhibitor of the
signaling molecule TBK1/IKKƐ, in order to cut the cost of CAR-T cell
production. In addition, ISIKOK-19 cells demonstrated a significantly
high level of cytotoxicity specifically against a CD19+ B-lymphocyte
cancer model, RAJI cells, in NOD/SCID mice.
Conclusion: This is the first report of preclinical assessment of
efficacy and safety analysis of CAR-T cells (ISIKOK-19) targeting
CD19-expressing B cells in relapsed/refractory ALL and NHL patients
in Turkey.
Objective:
To demonstrate the efficacy of tonsil brushing in patients with chronic tonsillitis to remove the microbial biofilm on the tonsil surface using an in vitro model.
Design:
Specimens from ...patients undergoing tonsillectomy were evaluated prior to and following surface cleaning methods, including rinsing and brushing, using scanning electron microscopy (SEM).
Patients:
The study population consisted of 25 randomly selected patients with chronic tonsillitis.
Interventions:
Specimens were collected and divided into four portions. Each portion received distinct surface cleaning methods and was immediately fixed for SEM examination.
Outcome measures:
The biofilm layer on the surface of the tonsils was examined using SEM. The density of the biofilm layer and the degree of persistence of the biofilm after rinsing and brushing were measured.
Results:
The surface biofilm of the tonsils in the first group, which were neither brushed nor rinsed, revealed a thick layer of biofilm on the mucosal surface. The second group of tonsils, which were only rinsed, also showed a thick layer of biofilm. The third group of tonsils, which were rinsed following gentle brushing using a soft toothbrush, showed a reduction in the thickness of the biofilm layer. The fourth group of tonsils, which were brushed with a hard brush, was almost devoid of a biofilm layer.
Conclusion:
Our results demonstrate that rinsing does not effectively remove the biofilm layer on the tonsil surface. The use of a harder brush was identified as a more powerful means of removing biofilm compared with a soft brush.
Background Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. Materials and Methods To ...investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 μg/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-α levels. Results Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-α level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-α or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. Conclusion Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury.
The anatomy of arterial bifurcations affects blood flow and has a significant role in the development of vascular disease. Therefore, it is important to know the structural characteristics of the ...Common Carotid Artery (CCA) and its branches for early onset of atherosclerosis in newborns.
The present study was conducted to evaluate the characteristics of CCA in newborn cadavers.
Eight carotid arteries obtained from newborn cadavers were used. The outflow to inflow area ratios was calculated to evaluate vessel diameters. Additionally, scanning electron and light microscopic investigations were conducted with tissue samples. The brachial artery of each cadaver was used as controls. Correlation between area ratios and atherosclerotic endothelial damage was determined.
Light microscopic investigations demonstrated that control group sections showed no positivity for Oil red O staining, while carotid bifurcation regions depicted widespread occurrence of intimal lipid accumulations. Scanning electron microscopic examination of control group sections presented regular endothelial topography, while carotid bifurcation region topography exhibited numerous blood cells and separated endothelial cells. Fibrin accumulation on endothelial surface in low area ratios was another important finding in the examination of its endothelial surface degeneration. The above-mentioned morphological findings seemed to be quite parallel to outflow to inflow area ratio data favouring low area and degeneration.
The correlation between area ratios and the histological characteristic of cerebral vessels of newborn cadavers indicate that early stages of atherosclerosis began in early embryologic life.
PDF
