Response to Oxidative Burst-Induced Hypoxia Is Associated With Macrophage Inflammatory Profiles as Revealed by Cellular Genome-Wide Association

BackgroundIn mammalian species, hypoxia is a prominent feature of inflammation. The role of hypoxia in regulating macrophage responses via alteration in metabolic pathways is well established. Recently, oxidative burst-induced hypoxia has been shown in murine macrophages after phagocytosis. Despite the available detailed information on the regulation of macrophage function at transcriptomic and epigenomic levels, the association of genetic polymorphism and macrophage function has been less explored. Previously, we have shown that host genetics controls approximately 80% of the variation in an oxidative burst as measured by nitric oxide (NO-). Further studies revealed two clusters of transcription factors (hypoxia-related and inflammatory-related) are under the genetic control that shapes macrophages’ pro-inflammatory characteristics.Material and MethodsIn the current study, the association between 43,066 autosomal Single Nucleic Polymorphism (SNPs) and the ability of MDMs in production of NO- in response to E. coli was evaluated in 58 Holstein cows. The positional candidate genes near significant SNPs were selected to perform functional analysis. In addition, the interaction between the positional candidate genes and differentially expressed genes from our previous study was investigated.ResultsSixty SNPs on 22 chromosomes of the bovine genome were found to be significantly associated with NO- production of macrophages. The functional genomic analysis showed a significant interaction between positional candidate genes and mitochondria-related differentially expressed genes from the previous study. Further examination showed 7 SNPs located in the vicinity of genes with roles in response to hypoxia, shaping approximately 73% of the observed individual variation in NO- production by MDM. Regarding the normoxic condition of macrophage culture in this study, it was hypothesized that oxidative burst is responsible for causing hypoxia at the cellular level.ConclusionThe results suggest that the genetic polymorphism via regulation of response to hypoxia is a candidate step that perhaps shapes macrophage functional characteristics in the pathway of phagocytosis leading to oxidative burst, hypoxia, cellular response to hypoxia and finally the pro-inflammatory responses. Since all cells in one individual carry the same alleles, the effect of genetic predisposition of sensitivity to hypoxia will likely be notable on the clinical outcome to a broad range of host-pathogen interactions

Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics.

Reactive Nitrogen Species (RNS) are a group of bactericidal molecules produced by macrophages in response to pathogens in a process called oxidative burst. Nitric oxide (NO-) is a member of RNS produced from arginine by inducible Nitric Oxide Synthase (iNOS) enzyme. The activity of iNOS and production of NO- by macrophages following stimulation is one of the indicators of macrophage polarization towards M1/proinflammatory. Production of NO- by bovine monocyte-derived macrophage (MDM) and mouse peritoneal macrophages has been shown to be strongly associated with host genetic with the heritability of 0.776 in bovine MDM and 0.8 in mouse peritoneal macrophages. However, the mechanism of genetic regulation of macrophage response has remained less explored. In the current study, the transcriptome of bovine MDMs was compared between two extreme phenotypes that had been classified as high and low responder based on NO- production. The results showed that 179 and 392 genes were differentially expressed (DE) between high and low responder groups at 3 and 18 hours after exposure to Escherichia coli, respectively. A set of 11 Transcription Factors (TFs) (STAT1, IRF7, SPI1, STAT4, IRF1, HIF1A, FOXO3, REL, NFAT5, HIC1, and IRF4) at 3 hours and a set of 13 TFs (STAT1, IRF1, HIF1A, STAT4, ATF4, TP63, EGR1, CDKN2A, RBL1, E2F1, PRDM1, GATA3, and IRF4) at 18 hours after exposure to E. coli were identified to be differentially regulated between the high and low responder phenotypes. These TFs were found to be divided into two clusters of inflammatory- and hypoxia-related TFs. Functional analysis revealed that some key canonical pathways such as phagocytosis, chemotaxis, antigen presentation, and cell-to-cell signalling are enriched among the over-expressed genes by high responder phenotype. Based on the results of this study, it was inferred that the functional characteristics of bovine MDMs are associated with NO-based classification. Since NO- production is strongly associated with host genetics, this study for the first time shows the distinct proinflammatory profiles of macrophages are controlled by the natural genetic polymorphism in an outbred population. In addition, the results suggest that genetics can be considered as a new dimension in the current model of macrophage polarization which is currently described by the combination of stimulants, only

Production of Low-Fat Camel Milk Functional Ice creams Fortified with Camel Milk Casein and its Antioxidant Hydrolysates

 Background and objective: The objective of this study was to produce functional low-fat camel milk ice creams enriched with native camel milk casein or its antioxidant hydrolysates produced by chymotrypsin.Material and methods: Native or hydrolyzed camel milk caseins (0, 2 and 4%) were added to camel milk low-fat ice creams. Hydrolysates were characterized for molecular weights and antioxidant activities. Physical (hardness, overrun and melting resistance) and sensorial attributes of the final products were assessed.Results and conclusion: Results showed that the chymotrypsin-mediated hydrolysis significantly (P<0.05) increased 2,2′-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity of the native camel milk casein. Apparent viscosity and consistency coefficient of the ice creams were increased by addition of proteins and hydrolysates due to their water holding capacity. Protein/hydrolysates-fortified samples showed higher melting resistances but lower overruns and softer textures, compared to control ice creams with no added native or hydrolyzed camel milk casein. Sensory analysis showed that only samples enriched with 2% of casein hydrolysate included sensory properties similar to those of control camel milk low-fat ice creams and other samples received lower sensory scores. Generally, this study has suggested that camel milk can be used to produce low-fat ice creams. Properties of these ice creams can be modified by adding various concentrations of native and hydrolyzed camel milk caseins.Conflict of interest: The authors declare no conflict of interest

Distinct miRNA profile of cellular and extracellular vesicles released from chicken tracheal cells following avian influenza virus infection

Innate responses provide the first line of defense against viral infections, including the influenza virus at mucosal surfaces. Communication and interaction between different host cells at the early stage of viral infections determine the quality and magnitude of immune responses against the invading virus. The release of membrane-encapsulated extracellular vesicles (EVs), from host cells, is defined as a refined system of cell-to-cell communication. EVs contain a diverse array of biomolecules, including microRNAs (miRNAs). We hypothesized that the activation of the tracheal cells with different stimuli impacts the cellular and EV miRNA profiles. Chicken tracheal rings were stimulated with polyI:C and LPS from Escherichia coli 026:B6 or infected with low pathogenic avian influenza virus H4N6. Subsequently, miRNAs were isolated from chicken tracheal cells or from EVs released from chicken tracheal cells. Differentially expressed (DE) miRNAs were identified in treated groups when compared to the control group. Our results demonstrated that there were 67 up-regulated miRNAs, 157 down-regulated miRNAs across all cellular and EV samples. In the next step, several genes or pathways targeted by DE miRNAs were predicted. Overall, this study presented a global miRNA expression profile in chicken tracheas in response to avian influenza viruses (AIV) and toll-like receptor (TLR) ligands. The results presented predicted the possible roles of some DE miRNAs in the induction of antiviral responses. The DE candidate miRNAs, including miR-146a, miR-146b, miR-205a, miR-205b and miR-449, can be investigated further for functional validation studies and to be used as novel prophylactic and therapeutic targets in tailoring or enhancing antiviral responses against AIV

A trend of Medical Negligence in Laser Therapy in the Capital City: A Nine-Year Survey

Background: the purpose of the present study is to investigate the common causes of injuries, claims, and decisions related to laser therapy medical malpractice during a nine-year survey. Study design: This study is a retrospective descriptive study. Methods: The legal documents in the coroner’s Office of Forensic Medicine were investigated in a national database from 2012 to 2020 in Tehran, Iran. The frequency and nature of the cases, including the year of litigation, the location and certificate of the provider, the injury sustained, the cause of legal action and judgment were collected. Results: Three hundred and eighty-three cases related to injury from laser therapy were registered in the coroner’s Office of Forensic Medicine during the study period. The incidence of litigation related to laser surgery showed an increasing trend, with a peak occurrence in 2020. Laser hair removal was the most common (51.2%) litigated procedure. General practice operators (48%) recorded the highest rate of laser-related medical complaints. lack of skill was the most common reason for failure. Among 383 cases with public decisions, 62.4% of them were fault liability in paid judgment. Conclusions: Medical claims related to laser application are increasing. However, as it is clear, the growth of laser technology and the increasing demand for lasers in medical science require more surveillance to avoid probable injuries and improve patient safety, especially surveillance of the physicians who work outside the scope of their specialty.&nbsp

Genetic selection of cattle for improved immunity and health

The immune system is a sensing structure composed of tissues and molecules that are well integrated with the neuroendocrine system. This integrate system ensures non-self from self-discrimination. In this capacity the immune system provides detection and protection from a wide range of pathogens. In mammals, the immune system is regulated by several thousand genes (8-9% of the genome) which indicate its high genetic priority as a critical fitness trait providing survival of the species. Identifying and selectively breeding livestock with the inherent ability to make superior immune responses can reduce disease occurrence, improve milk quality and increase farm profitability. Healthier animals also may be expected to demonstrate improvements in other traits, including reproductive fitness. Using the University of Guelph’s patented High Immune Response technology it is possible to classify animals as high, average, or low responders based on their genetic estimated breeding value for immune responsiveness. High responders have the inherent ability to produce more balanced and robust immune responses compared with average or low responders. High responders dairy cattle essentially have about one-half the disease occurrence of low responders, and can pass their superior immune response genes on to future generations thereby accumulating health benefits within the dairy herd

The Effect of Planting Density and Different Nitrogen and Phosphor Application Rates on Saffron Yield

ABSTRACT Increasing the saffron yield as a source of economic income has an effective role in the economic development. Selecting a proper planting density and using nitrogen and phosphor fertilizers are important for increasing saffron yield production. This study was conducted at the Research Farm of the Islamic Azad University, Karaj branch, Iran, in a factorial experiment in the form of a randomized complete block design with three replications. Treatments included three planting densities (120 corms/4.5 m 2 , 180/4.5 and 240/4.5), application of three nitrogen fertilizer rates (50, 75 and 100 kg/ha) and application of three phosphor fertilizer rates (25, 50 and 100 kg/ha). Analysis of variance showed the significant effect of planting density and nitrogen fertilizer on the flower number, flower fresh weight and fresh weight and dry weight of stigma (P≤0.01). Phosphor fertilizers had no effect on the measured traits. Moreover, length of stigma and style were not affected by the treatments. Generally, the three-fold interaction of the highest planting density × 75 kg N/ha × 100 kg P/ha was the most effective treatment compared with the others

Evaluation of Anti-CCP Positive in Patients with Systemic Lupus Erythematosus Referred to Loghman Hakim Hospital between 2007-2017; A Descriptive Study

Background: It has been found that some patients with Systemic lupus erythematosus (SLE) may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. SLE patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients in Loghman Hakim hospital, Tehran, Iran.Method and Materials: One hundred fourteen SLE patients were studied for anti-CCP. Demographic features and prevalence serum positive Anti-CCP were measured in studied patient.Results: In this study we evaluate 11 men and 103 women. The mean age of patients was 40.26±14.54 y/o. Anti-CCP was positive in 20 of 114 SLE patients. In Anti-CCP positive group also there was 3 men and 17 women with mean age of 45.7±13.Conclusion: We found that 17.5 % of Iranian patients with SLE have positive anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually. Key Words: Anti-CCP, Rheumatoid arthritis, Systemic lupus erythematosu