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Oct 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4296
Das SatadalCorresponding author
Genetic Research Unit, Heritage Institute of Technology, Kolkata-700107
Some evidence confirms the paradoxical beneficial role of harmful antigens when used in highly diluted forms. In this experiment, we observed cytokine gene expression changes in Gallus gallus embryo after challenge with Delta SARS-CoV-2 RBD spike protein antigen, from a concentration of 10 µg/mL to a series of highly diluted forms in ethanol, along with controls. We have also studied pre-and post- experimental combined sets of higher (10 µg/mL) and significantly lower antigen concentrations (attogram level). Attogram and zeptogram level concentrations of the antigen showed consistently remarkable up-regulation of INF-α among different cytokine gene expressions. INF-β gene expressions at the zeptogram level of the antigen showed consistent changes, although not so outstanding. The pre-experimental set having attogram level antigen administered first, followed by a 10µg/mL antigen challenge, showed excellent cytokine balance. Other experimental groups, including the control sets, showed variable results at different concentrations.
May 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3345
Ozcelik FatihCorresponding author
University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Medical Biochemistry, Istanbul, Turkey
While the COVID-19 pandemic has raised concerns about the future of people worldwide, it has made it necessary to take measures with high economic costs, including quarantine. We consider it is more logical for some scientists to investigate time-saving treatment options until vaccination studies, which are started to be studied rapidly, are accomplished or specific antiviral agents are found. In this context, treatment combinations of one or more of the immune modulators known as cytokines, which can stimulate or accelerate the immune system, should be tried. In our opinion, although such options are not as effective as specific treatments such as vaccines, such options will offer highly effective alternatives in times of emergency. For this reason, we found it appropriate to make a reminder by preparing a broad review about interferon gamma, which is an antivirus and is an immunomodulator and which plays a critical role in humoral and cellular immunity.
Oct 2016 DOI 10.14302/issn.2572-3030.jcgb-16-1276
Hayashi TakumaCorresponding author
Dept. of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan,
Human uterine leiomyosarcoma (LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human uterine LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome beta subunit 9 (PSMB9)/b1i, an interferon (IFN)-g inducible factor, spontaneously develop uterine LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumour suppressive, and signaling pathways directly impact sarcomagenesis. The IFN-g pathway is important for control of tumour growth and invasion and, has been implicated in several malignant tumours. In this study, experiments with human tissues revealed a defective PSMB9/b1i expression in human uterine LMS that was traced to the IFN-g pathway and the specific effect of somatic mutations of Janus kinase (JAK1) molecule or promoter region on the transcriptional activation of PSMB9/b1i gene. Understanding the molecular mechanisms of human uterine LMS may lead to identification of new diagnostic candidates or therapeutic targets in human uterine LMS.
Jan 2022 DOI 10.14302/issn.2692-1537.ijcv-21-4051
Alabdely MayyadahCorresponding author
Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
Background As COVID-19 immunomodulation has been a part of interest for studies, it has been found that severe coronavirus disease 2019 (COVID-19) is associated with hyper-inflammatory response and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). This can progress to cytokine storm syndrome and eventually development of acute respiratory distress syndrome (ARDS). Interleukin-1 receptor antagonist (IL-1RA) is a protein that is a member of the interleukin 1 cytokine family. Monocyte chemoattractant protein 1 (MCP1) is a small cytokine that belongs to the CC chemokine family. Interferon gamma-induced protein 10 (IP-10) is a protein secreted by several cell types in response to Interferon-Gamma (IFN-γ). All of these have roles in the immune response and eventually development of a cytokine storm. Methods Serum levels of IL-1RA, MCP-1 and IP-10 were measured in a cohort of 21 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 4 uninfected controls. The study population was classified into severe, moderate, mild and controls. Results Serum levels of IL-1RA, MCP-1 and IP-10 were found to be elevated before the clinical deterioration. Conclusion These cytokines may play a role in early detection of disease severity especially in the pre-storm phase. Medications that target cytokines may prevent the development of an overt cytokine storm.
Dec 2021 DOI 10.14302/issn.2575-1212.jvhc-21-4034
Fernando Díaz-Otero,Corresponding author
CENID-Salud Animal e Inocuidad. Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP). Carretera México-Toluca, Km. 15.5, C.P. 05110, Ciudad de México, México.
In bovine tuberculosis (bTB), cellular, humoral, or both types of immune responses have been observed. The purpose of this study was to examine the immune status of tuberculous cows based on the differential cytokine gene expression associated with Th1 (IFN-γ, IL-2), or Th2 (IL-4, IL-10) responses. Twenty-three (23) cows belonging to a dairy herd located in a rural region of the State of Hidalgo, México, were selected for the study. Single Intradermal Comparative Cervical Tuberculin (SICCT) Test, Interferon-Gamma (IFN-γ) Release Assay (BOVIGAM), and Enzyme-Linked Immunosorbent Assay (ELISA) were used for detection of cattle infected by M. bovis. Thirteen cows were positive to all the tests (Group 1); ten cows were positive only to ELISA (Group 2), and the remaining Group (Group 3, control) included cows negative to all the tests. Peripheral blood mononuclear cells (PBMC) from animals were in vitro stimulated by bovin purified protein derivative (PPD), avian PPD, and Concanavalin A (Con A) mitogen for 72h. Changes in the levels of expression of mRNA of the respective cytokines was measured by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) using β-actin gene as internal control. In group 1, PPD bovis and Con A-stimulated cells exhibited high production of IFN-γ, IL-2 and IL-4, but not IL-10. In contrast, PPD avium-stimulated cells displayed a low production of cytokine transcripts. In group 2, cells showed a significant production of IL-10 in response to bovine PPD (P< 0.001). In the control group, a high production of IFN-γ and IL-2 was observed only in Con A-stimulated cells. Post-mortem examinations in animals of group 1 showed slight and medium lesions in lymph nodes, whereas in group 2, the lesions were more extensive. Results indicate differences on gene expression levels of cytokines considered to determine balance in Th1/Th2 response among the evaluated groups. In addition, high levels of antibodies against M. bovis and high IL-10 expression in PBMC together are indicators of progressive bTB when both tuberculin test and IFN-γ assay are negative in tuberculous anergic cattle. Inclusion of serology and IL-10 cytokine expression in in the diagnosis checklist improves detection of infected cattle to help control bovine tuberculosis.
Jul 2021 DOI 10.14302/issn.2766-8681.jcsr-21-3885
Jana SnehasisCorresponding author
Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.
Sepsis is a systemic inflammatory response to a confirmed or suspected infection. The transition from sepsis to septic shock causes high rate of mortality. The aim of this experiment was to evaluate the anti-inflammatory potential of the Biofield Energy Treated (Blessed) Proprietary Test Formulation and Biofield Energy Healing (Blessing) Treatment per se to Sprague Dawley rats on Cecal Slurry, LPS, and E. coli-induced systemic inflammatory response syndrome (SIRS) model. In this experiment, various proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, 1L-17, and interferon-γ (IFN-γ) were analysed using ELISA. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment remotely for about 3 minutes by a renowned Biofield Energy Healer Mr. Mahendra Kumar Trivedi. The level of TNF-α was significantly reduced by 40.50%, 85.36% (p≤0.01), 50.66% (p≤0.01), 87.38% (p≤0.01), and 58.63% (p≤0.01) in G5 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation), G6 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se to animals from day -15), G7 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation from day -15), G8 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se + Biofield Energy Treated test formulation from day -15), and G9 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se animals + untreated test formulation) groups, respectively as compared to the disease control (G2) group. Additionally, the level of IL-1β was decreased by 17.04%, 15.56%, and 12.59% in G6, G8, and G9 groups, respectively as compared to the untreated test formulation (G4) group. The level of IL-6 was significantly (p≤0.001) reduced by 36.18%, 50.24%, 43.25%, 52.69%, and 38.23% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of IL-10 was altered by 70.53%, 49.25%, 60.18%, 41.54%, and 58.89% in G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Moreover, the level of IL-12 was decreased by 30.24%, 31.67%, 29.82%, 45.77%, and 50.54% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. The level of IL-17 was reduced by 48.75%, 59.61%, 59.28%, 62.49%, and 58.65% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. IFN-γ expression was reduced by 49.56%, 24.09%, 23.7%, 56.98%, and 44.94% in G5, G6, G7, G8, and G9 groups, respectively than G2. Overall, the data suggested anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications in preventive treatment groups viz. G6, G7, G8, and G9.
May 2019 DOI 10.14302/issn.2328-0182.japst-19-2738
BARON AuroreCorresponding author
USMP Fleury Merogis, CH Sud Francilien
Rationale Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Prevalence of viral hepatitis C (HCV) is higher in prison environment in France than in the general population and is estimated to be 4,8%. The impact in prison environment is little-known as based on local studies. Inmate health care falls under USMP (prison setting medical unit), hospital specific units as by the january 18, 1994 law. Access to antiviral c treatment for inmates has always been difficult in France, would it be for interferon and ribavirin or use of protease inhibitors, with less than 20% of treated patients. French recommendations for HCV screening recommend systematic screening of inmates. The arrival of all oral therapies by direct antiviral agents (DAA) with shorter treatment times was an opportunity for doctors to propose a treatment and the patient to accept it. In 2014, the French guidelines recommended that HCV carriers in prison should systematically be treated independently of the stage of fibrosis. Objective of the Study PH8 Our objective was to evaluate the completion rate of an 8-week antiviral C treatment by sofosbuvir / ledipasvir regimen in non-cirrhotic genotype 1 patients in deprivation of liberty and achieve sustained virological response (SVR) and to measure the effectiveness of an 8-week treatment (by protocol analysis). Methodology prospective non-interventional multicenter trial among inmates with chronic hepatitis C genotype 1 with METAVIR fibrosis score F0 to F2 and who will receive a daily combination of sofosbuvir / ledipasvir for 8 weeks. Results 6 prison medical units included 115 consenting patients: there were 81% men, mean age 41 years (21 to 64 years). Route contamination was drug injection for 85%. HCV genotype was 1a for 74%, 1b for 24% and 2% none differenciated 1. Fibroscan mesure was available in 89 patients (mean score 3,5 KPa). Fibrotest was available in 37 patients with mean value 0.21. Eleven patients had Fibroscan and Fibrotest; 69% of patients were F0, 22% F1 and 9% F2. Average time between diagnosis and start of treatment was 3 weeks. We are sure that 109 patients (95%) completed DAA 8 weeks treatment; only 2 stopped DAA treatment before 8 weeks and 4 had no follow up after end of detention. HCV viral load was measured at W2 for 90 patients (78%), at W4 for 92 patients (78%), at end of treatment for 92 patients (78%), one month after treatment for 90 patients (78%) and 3 months after for 95 patients (93%). Only one viral load was positive, one month after treatment. Patient was retreated by sofosbuvir / velpastasvir. All HCV viral load 3 months after treatment negative; one patient took DAA only 6 weeks was cured. Conclusions In these study PH8, we observed completion rate of 94% for included patients in patient with 8 weeks ledipasvir/sofosbuvir regimen; data missed for only 4 patients and one relapsed. Short DAA treatment was efficient in prisoners and could be preferred in specific population.
Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2639
McCarthy OliviaCorresponding author
Diabetes Research Group, Medical School, Swansea University, Swansea, UK
Nine healthy individuals with a mean ± SD BMI of 22.0 ± 0.7 kg/m² and age of 20 ± 0.2 years, participated in this single-blind randomised, crossover trial investigating the impact of ingesting two different honeys (1) Tropical Forest Honey (TFH) and (2) Manuka Honey; strength 12+ (MAN) on circulating levels of plasma interferon gamma following ex-vivo lipopolysaccharide (LPS) stimulation. Blood samples were prepared into duplicate aliquots of whole blood (800 μl) and 100 μg/l of LPS was added to samples to give a final volume of 1 ml. Levels of IFN-γ in plasma fractions were measured via commercially available sandwich ELISA and all comparisons were made with paired data using the Wilcoxon Signed Rank test taking a significance level of 5%. Whilst significant intra-and-interpersonal variation was observed, IFN-γ concentrations remained statistically unchanged 48 hours after the ingestion of either honey (p=0.15). Thus, in this instance the type of honey did not influence the IFN-γ response to plasma samples spiked with LPS.
Dec 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2487
Fernando Díaz-OteroCorresponding author
Centro Nacional de Investigaciones Disciplinarias en Microbiología Animal, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias. Carretera México-Toluca, Km. 15.5, C.P. 05110, México D.F.
Parasitic infection by the Fasciola hepatica (F. hepatica) promotes susceptibility towards other infections, such as Mycobacterium bovis. As consequence, could affect diagnostic tests for this disease. Hence, the objective of this study was to assess the impact of F. hepatica coinfection on the most commonly used immunodiagnostic bovine tuberculosis (bTB) tests in field conditions in an enzootic area for both diseases. Thus, from a dairy herd located in Hidalgo State, México, displaying a 59.2% and 28% prevalence of fascioliasis and bTB, respectively. Sixty-one cows were analyzed based on their response towards bTB immunodiagnostic tests, such as Single Intradermal Comparative Tuberculin Test (SICTT), gamma-interferon test (BOVIGAM) and enzyme-linked immunosorbent assay (ELISA), along with the assessment of the F. hepatica parasite load and serodiagnosis by ELISA. Three study groups were formed according to test results. Group 1: coinfected (n=22). Group 2: non-parasitized cows, and positive for bTB tests (n=13) and Group 3: parasitized cows without tuberculosis (n=26). In addition, a group of cows kept in fascioliasis - and tuberculosis-free zones were included (Group 4, n=10). A non-parametric Kruskal-Wallis test and a Dunn test were applied to analyze the results. In Group 1, significant differences were observed regarding IFN-γ production, but not for antibody levels to M. bovis or reactivity towards bovine PPD in relation Group 2. While, Groups 1 and 3 did not display difference in antibody levels against F. hepatica. Differences were observed regarding tuberculosis and Fasciola diagnostic tests when both coinfected and infected groups were compared to controls. It is concluded that F. hepatica coinfection in tuberculous animals studied, depressed the production of IFN-γ towards bovine PPD under in vitro conditions, but its reactivity to the SICTT not show to be altered.
Aug 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1662
Díaz Otero FernandoCorresponding author
Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Centro Nacional de Investigación Disciplinaria en Microbiología Animal, Carretera México-Toluca, Km 15.5, D.F., 05110, México
Immunization of cattle with the bacillus Calmette-Guérin (BCG) vaccine, especially neonates, induces protection against Mycobacterium bovis (M. bovis) and has been proposed as a strategy for bovine tuberculosis (bTB) control. Therefore, the aim of this study was to evaluate the immune response induced under field conditions in neonatal calves vaccinated with BCG Phipps, a strain that has rarely been evaluated in the bovine population, using interferon (IFN)-γ and tuberculin tests, flow cytometry and enzyme-linked immunosorbent assay. Two groups (vaccinated and control) of 5 calves were monitored for 12 weeks, and increases in the in vitro IFN-γ production, the percentage of cluster of differentiation (CD)8+ T cells and the activation levels of CD4+ and CD8+ T cells were observed 3 to 4 weeks post-vaccination. Bovine purified protein derivative-specific IFN-γ production was increased about 4.8- and 5.5-fold in vaccinated animals compared to non-vaccinated animals 3 and 4 weeks post-vaccination respectively. CD8+ T cells of the vaccinated group were increased 1.6-, 1.5- and 1.6-fold at weeks 2, 3 and 4 respectively. Levels of activation were 1.7- and 1.9-fold higher for CD4+ T cells and 2.3- and 1.8-fold higher for CD8+ T cells in the vaccinated group at weeks 3 and 4 respectively in response to M. bovis antigens. However, no animals (vaccinated or control) showed positive results for the single intradermal comparative tuberculin test (SICTT). Therefore, our results indicate that vaccination with M. bovis BCG Phipps strain stimulated peripheral blood T cell activity and induced a cell-mediated immune response. In addition, vaccination did not interfere with the SICTT, as previously reported, which indicates that this vaccine could be successfully applied in bTB control campaigns.
Feb 2016 DOI 10.14302/issn.2374-9431.jbd-15-890
E. Buroker NormanCorresponding author
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Purpose Signal Transducer and Activator of Transcription 4 (STAT4) is important for signaling by interleukins (IL-12 and IL-23) and type 1 interferons and has been found to have several simple nucleotide polymorphisms (SNPs) associated with human disease. STAT4 SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theSTAT4 gene from 4 kb upstream of the transcriptional start site to 8.3 kb past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The STAT4 SNPs in the 70 kb intron between exon 2 and 3 are in linkage disequilibrium and have previously been found to be significantly associated with several vasculitis diseases as well as diabetes. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the STAT4 gene. These STAT4 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF STAT4 regulation. These regulatory changes were discussed with respect to changes in human health that result in disease.
May 2015 DOI 10.14302/issn.2470-0436.jos-14-527
Sanjay SrinivasanCorresponding author
Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore
A 66 year old Chinese male with a medical history of hypertension, diabetes mellitus and hepatitis B carrier was diagnosed with hepatocellular carcinoma in 2009. He underwent treatment with selective internal radiation spheres and sorafenib, and multiple cycles of chemotherapeutic agents such as bevacizumab, erlotinib, OXAFI ( intravenous oxaliplatin and doxorubicin given on days 1, 8 and 15 in a 28-day cycle, a daily continuous infusion of fluorouracil and subcutaneous interferon alfa-2b 5 million units administered thrice weekly), thalidomide, capecitabine, and rapamycin over the course of four years. Along the course of treatment, he developed pulmonary embolism and was initially started on anti-coagulation. Two months later, he developed hemoptysis and the anti-coagulants were stopped. During his routine ophthalmology visit for diabetic eye evaluation, he complained of blurring of vision of his left eye for the past four to five weeks. He was found to have central retinal vein occlusion (CRVO) of the left eye, associated with macular edema. Visual acuity was 6/15 for the right eye and 6/60 for the left eye. Eyelids, conjunctiva, cornea, anterior chamber, pupils, lens and ocular motility were normal. Humphrey visual field testing showed a superior arcuate and basal defect. This is the first reported case of CRVO in hepatocellular carcinoma. The etiology of CRVO is multifactorial, withhepatic malignancy, previous major surgery, multiple cycles of chemotherapy and cessation of anticoagulant therapyas possible aetiological factors. His background medical problems of diabetes and hypertension are further contributors.