Suppression Of Immune Function Research Articles

Current research status and prospects of ginseng's regulatory effect on immune dysfunction caused by "acute deficiency syndrome" of sepsis

Sepsis is a prevalent critical illness observed in emergency intensive care unit (ICU), characterized by life-threatening organ dysfunction caused by infection-induced inflammatory immune disorders in the body. The suppression of immune function plays a crucial role in the development and progression of sepsis. Traditional Chinese medicine theory of "acute deficiency syndrome" in sepsis shares similarities with the concept of "immunosuppression". According to this theory, ginseng is frequently utilized in clinical treatment of sepsis due to its ability to invigorate vitality and strengthen the body, playing a crucial role in tonifying deficiency and improving the overall health of patients. This paper provides a detailed discussion of the pathophysiological mechanisms of sepsis immune dysfunction and its correlation with "acute deficiency syndrome" in traditional Chinese medicine. It summarizes the current state of modern pharmacological research on ginseng's impact on the body's immune function, discusses relevant research progress and shortcomings regarding ginseng's therapeutic effects on immunosuppression in sepsis, and proposes future research directions.

The Effects of Fingolimod (FTY720) on Leukocyte Subset Circulation cannot be Behaviourally Conditioned in Rats

Suppression of immune functions can be elicited by behavioural conditioning using drugs such as cyclosporin A or rapamycin. Nevertheless, little is known about the underlying mechanisms and generalisability of this phenomenon. Against this background, the present study investigated whether the pharmacological properties of fingolimod (FTY720), an immunosuppressive drug widely applied to treat multiple sclerosis, can be conditioned in rats by means of taste-immune associative learning. For this purpose, a conditioned taste avoidance paradigm was used, pairing the presentation of a novel sweet drinking solution (saccharin or sucrose) as conditioned stimulus (CS) with therapeutically effective doses of FTY720 as unconditioned stimulus (US). Subsequent re-exposure to the CS at a later time point revealed that conditioning with FTY720 induced a mild conditioned taste avoidance only when saccharin was employed as CS. However, on an immunological level, neither re-exposure with saccharin nor sucrose altered blood immune cell subsets or splenic cytokine production. Despite the fact that intraperitonally administered FTY720 could be detected in brain regions known to mediate neuro-immune interactions, the present findings show that the physiological action of FTY720 is not inducible by mere taste-immune associative learning. Whether conditioning generalises across all small-molecule drugs with immunosuppressive properties still needs to be investigated with modified paradigms probably using distinct sensory CS. Moreover, these findings emphasize the need to further investigate the underlying mechanisms of conditioned immunomodulation to assess the generalisability and usability of associative learning protocols as supportive therapies in clinical contexts.Graphical To assess the potential of taste-immune associative learning mediated by specific brain regions (e.g., insular cortex, amygdala), the presentation of a novel taste (saccharin or sucrose) as conditioned stimulus was paired with injections of fingolimod (FTY720) as unconditioned stimulus. However, re-exposure to the conditioned stimulus did not elicit behaviourally conditioned immunosuppressive effects. Created with BioRender.com.

Diagnostic and prognostic significance of apelin-13, APJ for sepsis in the emergency department: A prospective study

ObjectivesThis study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). MethodsTwo hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4+ Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. ResultsThe plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4+ T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. ConclusionsApelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression.

Bacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs

Many bacteria use CRISPR–Cas systems to combat mobile genetic elements, such as bacteriophages and plasmids1. In turn, these invasive elements have evolved anti-CRISPR proteins to block host immunity2,3. Here we unveil a distinct type of CRISPR–Cas Inhibition strategy that is based on small non-coding RNA anti-CRISPRs (Racrs). Racrs mimic the repeats found in CRISPR arrays and are encoded in viral genomes as solitary repeat units4. We show that a prophage-encoded Racr strongly inhibits the type I-F CRISPR–Cas system by interacting specifically with Cas6f and Cas7f, resulting in the formation of an aberrant Cas subcomplex. We identified Racr candidates for almost all CRISPR–Cas types encoded by a diverse range of viruses and plasmids, often in the genetic context of other anti-CRISPR genes5. Functional testing of nine candidates spanning the two CRISPR–Cas classes confirmed their strong immune inhibitory function. Our results demonstrate that molecular mimicry of CRISPR repeats is a widespread anti-CRISPR strategy, which opens the door to potential biotechnological applications6.

The Cell-Autonomous Pro-Metastatic Activities of PD-L1 in Breast Cancer Are Regulated by N-Linked Glycosylation-Dependent Activation of STAT3 and STAT1.

PD-L1 has been characterized as an inhibitory immune checkpoint, leading to the suppression of potential anti-tumor immune activities in many cancer types. In view of the relatively limited efficacy of immune checkpoint blockades against PD-L1 in breast cancer, our recent study addressed the possibility that in addition to its immune-inhibitory functions, PD-L1 promotes the pro-metastatic potential of the cancer cells themselves. Indeed, our published findings demonstrated that PD-L1 promoted pro-metastatic functions of breast cancer cells in a cell-autonomous manner, both in vitro and in vivo. These functions fully depended on the integrity of the S283 intracellular residue of PD-L1. Here, using siRNAs and the S283A-PD-L1 variant, we demonstrate that the cell-autonomous pro-metastatic functions of PD-L1-tumor cell proliferation and invasion, and release of the pro-metastatic chemokine CXCL8-required the activation of STAT3 and STAT1 in luminal A and triple-negative breast cancer cells. The cell-autonomous pro-metastatic functions of PD-L1 were potently impaired upon inhibition of N-linked glycosylation (kifunensine). Site-specific mutants at each of the N-linked glycosylation sites of PD-L1 (N35, N192, N200, and N219) revealed that they were all required for PD-L1-induced pro-metastatic functions to occur; the N219 site was the main regulator of STAT3 and STAT1 activation, with accompanying roles for N192 and N200 (depending on the cell type). Using a T cell-independent mouse system, we found that cells expressing N35A-PD-L1 and N219A-PD-L1 had a significantly lower tumorigenic and metastatic potential than cells expressing WT-PD-L1. TCGA analyses revealed significant associations between reduced survival and high levels of α-mannosidase II (inferring on N-linked glycosylation) in breast cancer patients. These findings suggest that N-linked glycosylation of PD-L1 may be used to screen for patients who are at greater risk of disease progression, and that modalities targeting N-linked glycosylated PD-L1 may lead to the inhibition of its cell-autonomous pro-metastatic functions and to lower tumor progression in breast cancer.

Health Implications of Bioaccumulation of PAHs in Fluted Pumpkin (Telfairia occidentalis) and Waterleaf (Talinum fruticosum) along the Imo River Watershed, Imo State, Nigeria

The health implication of PAHs has been of great concern due to its contamination of the food chain. This study was carried out to identify the health challenges associated with the bioaccumulation of PAHs in Fluted Pumpkin (Telfairia occidentalis) and Waterleaf (Talinum fruticosum) along Imo River Watershed, Imo State, Nigeria. A total of 8 soil samples (0-30cm) were randomly collected from different activity areas on the watershed and analyzed for the presence of the 16 US-EPA priority PAHs in both soil and vegetable samples. The analysis of PAHs in the soil and vegetable samples were carried out in accordance with EPA 8270: (GC-MSD) and the results revealed that amongst the 16 US-EPA priority PAHs, eight of them were detected in the soil and vegetable samples. The total concentration of PAHs detected in the soil and vegetable samples were Naphthalene(0.146mg/kg), Acenaphthylene(0.010mg/kg), Acenaphthene(0.210mg/kg),Phenanthrene(0.021mg/kg),Anthracene(0.041mg/kg),Flouranthene(0.130mg/kg),Pyrene(0.020mg/kg),Benzo(b)fluoranthene(8.641mg/kg) and Naphthalene(0.090mg/kg),Acenaphthene(0.011mg/kg),Fluorene(0.010mg/kg),Phenanthrene(0.230mg/kg),Anthracene(0.190mg/kg),Flouranthene(0.010mg/kg),Benzo(b)fluoranthene(2.711mg/kg),I(1,2,3-cd)PY(0.540mg/kg) respectively. The decreasing order for individual PAHs concentration in the soil and vegetable samples within the study area were Benzo(b)Flouranthene>Acenaphthene>Naphthalene>Fluoranthene>Anthracene> Phenanthrene> Pyrene> Acenaphthelyne and Benzo(b) Flouranthene>I(1,2,3-cd)PY> Phenanthrene> Anthracene> Naphthalene>Acenaphthene> Fluorene>Fluoranthene respectively. For both soil and vegetables, total PAHs concentrations recorded in Obowo zone were observed to be higher than Okigwe zone. The result also revealed high values of PAHs in the edible vegetable samples collected around abattoirs and abandoned waste dump. It is therefore evident from this study that abattoirs and waste dumps have the potential to emit huge amount of PAHs to soil resource, which is taken up by edible vegetables leading to several health challenges when the vegetables are consumed. Different exposure to PAHs results in immune function suppression, cataracts, kidney and liver damage, skin inflammation, asthma, nausea, vomiting, eye irritation, diarrhea, confusion, lung and other cancers and probably death in chronic cases. There is need for public education on the consumption of vegetables grown in and around abattoirs and areas dominated by waste dumps.

Assessing the Effects of Nicotinamide Mononucleotide Supplementation on Pulmonary Inflammation in Male Mice Subchronically Exposed to Ambient Particulate Matter.

Chronic lung injury and dysregulated cellular homeostasis in response to particulate matter (PM) exposure are closely associated with adverse health effects. However, an effective intervention for preventing the adverse health effects has not been developed. This study aimed to evaluate the protective effects of nicotinamide mononucleotide (NMN) supplementation on lung injury and elucidate the mechanism by which NMN improved immune function following subchronic PM exposure. Six-week-old male C57BL/6J mice were placed in a real-ambient PM exposure system or filtered air-equipped chambers (control) for 16 wk with or without NMN supplementation in drinking water (regarded as , , Con-NMN and Exp-NMN groups, respectively) in Shijiazhuang City, China (/group). The effects of NMN supplementation () on PM-induced chronic pulmonary inflammation were assessed, and its mechanism was characterized using single-cell transcriptomic sequencing (scRNA-seq) analysis of whole lung cells. The NMN-treated mice exhibited higher levels in multiple tissues. Following 16-wk PM exposure, slightly less pulmonary inflammation and less collagen deposition were noted in mice with NMN supplementation in response to real-ambient PM exposure (Exp-NMN group) compared with the group (all ). Mouse lung tissue isolated from the Exp-NMN group was characterized by fewer neutrophils, monocyte-derived cells, fibroblasts, and myeloid-derived suppressor cells induced by subchronic PM exposure as detected by scRNA-seq transcriptomic analysis. The improved immune functions were further characterized by interleukin-17 signaling pathway inhibition and lower secretion of profibrotic cytokines in the Exp-NMN group compared with the group. In addition, reduced proportions of differentiated myofibroblasts and profibrotic interstitial macrophages were identified in the NMN-supplemented mice in response to PM exposure. Furthermore, less immune function suppression and altered differentiation of pathological cell phenotypes NMN was related to intracellular lipid metabolism activation. Our novel findings suggest that NMN supplementation mitigated PM-induced lung injury by regulating immune functions and improving lipid metabolism in male mice, providing a putative intervention method for prevention of human health effects associated with PM exposure. https://doi.org/10.1289/EHP12259.

Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy.

The cell surface enzyme CD73 is increasingly appreciated as a pivotal non-redundant immune checkpoint (IC) in addition to PD-1/PD-L1 and CTLA-4. CD73 produces extracellular adenosine (eADO), which not only inhibits antitumor T cell activity via the adenosine receptor (AR) A2AR, but also enhances the immune inhibitory function of cancer-associated fibroblasts and myeloid cells via A2BR. Preclinical studies show that inhibition of the CD73-adenosinergic pathway in experimental models of many solid tumors either as a monotherapy or, more effectively, in combination with PD-1/PD-L1 or CTLA-4 IC blockades, improves antitumor immunity and tumor control. Consequently, approximately 50 ongoing phase I/II clinical trials targeting the CD73-adenosinergic IC are currently listed on https://clinicaltrials.gov. Most of the listed trials employ CD73 inhibitors or anti-CD73 antibodies alone, in combination with A2AR antagonists, and/or with PD-1/PD-L1 blockade. Recent evidence suggests that the distribution of CD73, A2AR and A2BR in tumor microenvironments (TME) is heterogeneous, and this distribution affects CD73-adenosinergic IC function. The new insights have implications for the optimally effective, carefully tailored approaches to therapeutic targeting of this essential IC. In the mini-review, we briefly discuss the cellular and molecular mechanisms of CD73/eADO-mediated immunosuppression during tumor progression and therapy in the spatial context of the TME. We include preclinical data regarding therapeutic CD73-eADO blockade in tumor models as well as available clinical data from completed trials that targeted CD73-adenosinergic IC with or without PD-1/PD-L1 inhibitors and discuss factors that are potentially important for optimal therapeutic outcomes in cancer patients.

MicroRNA-211 Regulates Proliferation, Expansion, and Immune Inhibitory Function of Myeloid-Derived Suppressor Cells via Mediation of CHOP Expression

ABSTRACT Background Myeloid-derived suppressor cells (MDSCs) are capable of effectively repressing immune responses against tumors and orchestrating the tumor microenvironment, which can promote tumor angiogenesis and metastasis. The pathway networks used to modulate tumor-expanded MDSC accumulation and function remain unclear. This study identified microRNA-211 (miR-211), whose expression was significantly decreased by factors derived from tumors. Methods miR-211 was assumed to be critical in modulating the accumulation and activity of MDSCs isolated from ovarian cancer (OC)-bearing mice by targeting C/EBP homologous protein (CHOP). Results The upregulation of miR-211 repressed MDSC proliferation, inhibited MDSC immunosuppressive functions, and increased the number of co-incubated CD4+ and CD8+ cells. Furthermore, overexpression of miR-211 led to decreased activities of the NF-κB, PI3K/Akt, and STAT3 pathways and the subsequent downregulation of matrix metalloproteinases to promote tumor cell invasion and metastasis. CHOP overexpression counteracted the effects of miR-211 elevation on these phenotypic changes. Upregulation of miR-211 also dramatically impaired the activity of MDSCs and suppressed OC tumor growth in vivo. Conclusion These results indicated that the miR-211-CHOP axis in MDSCs plays an essential role in the metastasis and proliferation of tumor-expanded MDSCs and might represent a promising cancer treatment target.

518 Identification of Tumor Infiltrating Leukocytes in Glioblastoma and Clinical Outcomes

INTRODUCTION: Glioblastoma (GBM) accounts for 60% of all malignant brain tumors in adults with a dismal 5-year survival rate of 5%. Treatment challenges stem from GBM’s intricate biology, therapy-resistant tumor cells, favorable milieu, invasive properties, and immunosuppressive tumor-infiltrating leukocytes (TIL). These cells are pro-repair and provide an immune inhibitory function, thereby conferring an elusive and protective phenotype to malignant cells. The clinical association with outcomes and response of these cell types to chemotherapeutics remains largely uncharacterized. METHODS: Fresh GBM tumor samples were collected. Using flow cytometry, tumor-specific and TIL-specific antibodies are used to label these cells. GBM and TIL phenotype within each sample is correlated to patient outcome to understand how those are related to the successes and failures of treatment. In addition, these cells are subjected to a different chemotherapeutics to assess their response to therapy. RESULTS: Patients’ mean age was 66.3 y, 15 patients (62%) were female. There was variable expression of EFGR and PDFRA within and between tumors. TIL represent approximately 20% of the cells in the samples. Myeloid cells represent most TIL (86%) in most samples. MGMT promoter un-methylated status was associated with high proportion of MDSC (34%) and poor survival. Correlations between TIL and GBM immunophenotypes were observed such as an inverse correlation between EGFR expression and MDSCs. Drug-screening is currently underway. CONCLUSIONS: The MDSC and EGFR inverse correlation suggests a possible relationship between tumor cells and TIL, supported by studies showing a release of pro-repair cytokines with EGFR signaling. Similarly, T-cells were positively correlated with EGFR expression. These findings strengthen the evidence of the protective role of TIL in GBM. Chemotherapeutics are being currently studied to assess impact on tumor viability.

BDE-47 Induces Immunotoxicity in RAW264.7 Macrophages through the Reactive Oxygen Species-Mediated Mitochondrial Apoptotic Pathway

Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.

Single-cell transcriptome analysis reveals heterogeneity and convergence of the tumor microenvironment in colorectal cancer.

Colorectal cancer (CRC) ranks second for mortality and third for morbidity among the most commonly diagnosed cancers worldwide. We aimed to investigate the heterogeneity and convergence of tumor microenvironment (TME) in CRC. We analyzed the single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO) database and identified 8 major cell types and 25 subgroups derived from tumor, para-tumor and peripheral blood. In this study, we found that there were significant differences in metabolic patterns, immunophenotypes and transcription factor (TF) regulatory patterns among different subgroups of each major cell type. However, subgroups manifested similar lipid metabolic patterns, immunosuppressive functions and TFs module at the end of the differentiation trajectory in CD8+ T cells, myeloid cells and Fibroblasts. Meanwhile, TFs regulated lipid metabolism and immunosuppressive ligand-receptor pairs were detected by tracing the differentiation trajectory. Based on the cell subgroup fractions calculated by CIBERSORTx and bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA), we constructed an immune risk model and clinical risk model of CRC which presented excellent prognostic value. This study identified that the differentiation was accompanied by remodeling of lipid metabolism and suppression of immune function, which suggest that lipid remodeling may be an important trigger of immunosuppression. More importantly, our work provides a new perspective for understanding the heterogeneity and convergence of the TME and will aid the development of prognosis and immunotherapies of CRC patients.

Prognostic stratification based on the levels of tumor-infiltrating myeloid-derived suppressor cells and PD-1/PD-L1 axis in locally advanced rectal cancer.

Although rectal cancer remains somewhat sanctuary to the contemporary immunotherapy, there is increasing knowledge on clinical implications of anti-tumor immunity. This study evaluated the prognostic relevance of two immune-inhibitory functions, myeloid-derived suppressor cells (MDSCs) and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis. Study cohort is comprised of 165 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by definitive resection. Using postsurgical tissue microarrays, the number of MDSCs, PD-1+/CD8+ tumor-infiltrating lymphocyte (TIL) ratio, and PD-L1 expression scores in stromal immune cells and tumor cells were assessed. Positive correlation was observed between the PD-1+/CD8+ TIL ratio and number of MDSCs (P < 0.001). The greater the immune infiltrates, the higher the PD-L1 immune cell score (P < 0.001). MDSCHigh, PD-1+/CD8+ TILHigh, PD-L1 immune cell scoreLow, and PD-L1 tumor H-scoreHigh were associated with worse disease-free survival (DFS) (P < 0.001, P = 0.042, 0.047, and P < 0.001, respectively). To integrate the adverse effects of MDSCHigh, PD-1+/CD8+ TILHigh, and either PD-L1 immune cell scoreLow (set I) or tumor H-scoreHigh (set II), prognostic risks were stratified according to the number of factors: 0, 1, and 2-3 (P < 0.001 for I and II). On multivariate analyses, patients with multiple risk factors for set I and II had worse prognosis (P < 0.001; 2-3 vs. 0 for models I and II), and the two prognostic models had acceptable predictability. In this study, integration of the prognostic impact of MDSCs and PD-1/PD-L1 stratified the long-term risks of patients with locally advanced rectal cancer. Thus, further exploration could be focused to the identified subset of patients carrying worse prognosis, where potential benefits could be derived by targeting the two components contributing to the immunosuppressive microenvironment.

The expression pattern of immune-related genes and characterization of tumor immune microenvironment: predicting prognosis and immunotherapeutic effects in cutaneous melanoma

BackgroundIncreasing evidences have revealed the tumor immune microenvironment not only has vital impacts on the origin, progression, and metastasis of tumors significantly but also influences the response to immunotherapy. Nonetheless, to date, the well-rounded expression pattern of immune-related genes in cutaneous melanoma and the comprehensive characterization of tumor immune microenvironment remain not clearly elucidated.MethodWe comprehensively evaluated the well-rounded expression pattern of immune-related genes of 686 patients with cutaneous melanoma based on immune-related genes with prognostic value and systematically correlated the expression pattern of these genes with the comprehensive characterization of tumor immune microenvironment. The IRGscore was constructed to quantify immunological function of individual using principal component analysis algorithms.ResultThree distinct immune subtypes were determined with obvious survival differences. Melanoma patients with high IRGscore was characterized by comprehensive suppression of immune function, showing much poorer prognosis and efficacy for immunotherapy, while the low IRGscore means the robust activation of immune function and the better effect of immunotherapy, which may be responsible for a better prognosis. Besides, the prognostic ability of IRGscore was further validated by the independent dataset of stomach cancers. Furthermore, the predictive effect of immunotherapeutic benefits of IRGscore was demonstrated by the independent dataset of melanoma patients accepting immunotherapy and another predictive model for immunotherapy.ConclusionIRGscore could serve as an independent immunotherapeutic and prognostic predictor, thereby facilitating the identification of appropriate candidates with cutaneous melanoma for immunotherapy and the formulation of individualized therapeutic approaches.

Blood Transmission of Corona Virus Disease 2019. Are there any Threat?

Background: Corona Virus infection is rapidly expanding and has a significant worldwide influence on the status of health and the economic process. Aim: Performing a literature search to investigate possible impacts of transmission of COVID-19 disease through blood transfusion process in health care system, and disease prevalence. Methods: Internet search in scientific publications and collecting data regarding different viral transmission routes, viral detection and disease diagnosis methods, what are the potential problems and risks in COVID-19 management, and COVID-19 protective measures to undertake during blood transfusion. Discussion and Conclusion: Coronavirus spreads mostly by droplets produced by infected persons while coughing, sneezing, or speaking. Different Covid-19 diagnosis methods include Computed Tomography (CT) scan, reverse transcription-polymerase chain reaction, antibody testing (IgG, and IgM), and biochemical tests. Different disease management risks may occur including antibiotic resistance, occupational stress, immune function suppression or dysregulation, pharmacodynamic interactions like prolongation of the QT interval. Although the findings indicated that blood transfusion did not transmitted coronavirus, but protective measures should be undertaken during blood transfusion process in healthcare facilities and blood transfusion centers. This will aid in mitigating viral transmission and associated management risks that may occur.

Effect of daidzein on growth, development and biochemical physiology of insect pest, Spodoptera litura (Fabricius)

Anti- insecticidal potential of daidzein was studied by feeding second instar larvae of Spodoptera litura (Fabricius) on artificial diet incorporated with different concentrations (5 ppm, 25 ppm, 125 ppm, 625 ppm) of diadzein. Results revealed high larval mortality, prolongation of pupal and total developmental period of the larvae treated with diadzein. Anti-nutritional/post ingestive toxicity of diadzein was also revealed by the decrease in the nutritional indices such as relative growth rate (RGR), relative consumption rate (RCR), efficiency of conversion of digested food (ECD), efficiency of conversion of ingested food (ECI) and approximate digestibility (AD). The suppression of immune function due to decline in the total hemocytes count was also observed in treated S. litura larvae. Profiles of detoxifying enzymes viz. superoxide dismutases (SOD), catalase (CAT), ascorbate peroxidases (APOX) and glutathione S-transferase (GST) were also significantly increased with diadzein treatment. The hydrogen peroxide content (H2O2), lipid peroxide content (LP) and protein carbonyl content were also significantly enhanced in the treated larvae thus, indicating oxidative stress in the insect. Our findings suggest that daidzein can be used as the alternative to conventional pesticides for controlling S. litura population.

Tafazzin deficiency in mouse mesenchymal stem cells promote reprogramming of activated B lymphocytes toward immunosuppressive phenotypes.

Barth Syndrome (BTHS) is a rare X-linked genetic disorder caused by mutation in the TAFAZZIN gene. Tafazzin (Taz) deficiency in BTHS patients results in an increased risk of infections. Mesenchymal stem cells (MSCs) are well known for their immune-inhibitory function. We examined how Taz-deficiency in murine MSCs impact their ability to modulate the function of lipopolysaccharide (LPS)-activated wild type (WT) B lymphocytes. MSCs from tafazzin knockdown (TazKD) mice exhibited a reduction in mitochondrial cardiolipin compared to wild type (WT) MSCs. However, mitochondrial bioenergetics and membrane potential were unaltered. In contrast, TazKD MSCs exhibited increased reactive oxygen species generation and increased glycolysis. The increased glycolysis was associated with an elevated proliferation, phosphatidylinositol-3-kinase expression and expression of the immunosuppressive markers indoleamine-2,3-dioxygenase, cytotoxic T-lymphocyte-associated protein 4, interleukin-10, and cluster of differentiation 59 compared to controls. Inhibition of glycolysis with 2-deoxyglucose attenuated the TazKD-mediated increased expression of cytotoxic T-lymphocyte-associated protein 4 and interleukin-10. When co-cultured with LPS-activated WT B cells, TazKD MSCs inhibited B cell proliferation and growth rate and reduced B cell secretion of immunoglobulin M compared to controls. In addition, co-culture of LPS-activated WT B cells with TazKD MSCs promoted B cell differentiation toward interleukin-10 secreting plasma cells and B regulatory cells compared to controls. The results indicate that Taz deficiency in MSCs promote reprogramming of activated B lymphocytes toward immunosuppressive phenotypes.

The Role of Dexmedetomidine in Tumor-Progressive Factors in the Perioperative Period and Cancer Recurrence: A Narrative Review.

Dexmedetomidine, a specific α2 adrenergic receptor agonist, is highly frequently used in the perioperatively for its favorable pharmacology, such as mitigating postoperative cognitive dysfunction. Increasing attention has been recently focused on the effect of whether dexmedetomidine influences cancer recurrence, which urges the discussion of the role of dexmedetomidine in tumor-progressive factors. The pharmacologic characteristics of dexmedetomidine, the tumor-progressive factors in the perioperative period, and the relationships between dexmedetomidine and tumor-progressive factors were described in this review. Available evidence suggests that dexmedetomidine could reduce the degree of immune function suppression, such as keeping the number of CD3+ cells, NK cells, CD4+/CD8+ ratio, and Th1/Th2 ratio stable and decreasing the level of proinflammatory cytokine (interleukin 6 and tumor necrosis factor-alpha) during cancer operations. However, dexmedetomidine exhibits different roles in cell biological behavior depending on cancer cell types. The conclusions on whether dexmedetomidine would influence cancer recurrence could not be currently drawn for the lack of strong clinical evidence. Therefore, this is still a new area that needs further exploration.

Global Dysphagia Scale Detects Swallowing Disorder Following a Clinical Dose of Buprenorphine

Opioid use is associated with increased risk of chest infection due to opioid suppression of immune function, ventilation, cough, and secretion mobilization. Buprenorphine is a highly lipophilic, semi‐synthetic partial agonist of the mu opioid receptor. Intramuscular buprenorphine is commonly used for post‐operative analgesia at a dose range of 0.01‐0.04 mg/kg in the cat. While buprenorphine is considered to have a low side effect profile, its effects on the pharyngeal phase of swallow are unknown. We hypothesized that administration of opioid would result in clinically meaningful decline of pharyngeal swallow function. Experiments were performed on healthy adult cats (12 months old). Animals were administered intramuscular buprenorphine (0.015 mg/kg) q12 hours for 48 hours. One hour after the last dose was given, videofluoroscopic swallow studies were performed to evaluate the effects of the drug on swallow function. Animals were presented with 40% by volume barium sulfate in tuna water mixed to a thin consistency, and all animals ate voluntarily. Images were recorded in the lateral plane at 30 frames/second and compared to control feeding assessments using the Global Dysphagia Scale (GDS), a novel tool developed to rate swallow function in the cat. The GDS consists of an Airway Invasion Scale (AIS) and relevant components of the Modified Barium Swallow Impairment Profile (MBSImP), a standardized protocol for swallow assessment. The AIS is a 10‐point scale where scores of 0‐1 are normal, scores of 2‐4 indicate laryngeal penetration, and scores of 5‐9 indicate tracheobronchial aspiration. Four components of the MBSImP were included: Initiation of the pharyngeal swallow, pharyngeal stripping wave, pharyngoesophageal segment opening, and pharyngeal residue. The GDS rating was derived by adding the AIS and MBSImP sub‐totals. During control assessments mean GDS was 5.5 ± 1.3, and aspiration was not detected in any animal. On buprenorphine, mean GDS was 11.25 ± 4.2, and 50% of animals exhibited large volume tracheobronchial aspiration. In conclusion, after 48 hours on buprenorphine, airway protection during swallow failed without appreciable response in 50% of animals (no cough, throat clear, or cessation of eating). Our success in producing dysphagia (significant but varying by animal) with relatively small doses of opioid has potential implications for predicting aspiration pneumonia in post‐surgical clinical cases.

The immunotoxicity of decabromodiphenyl ether (BDE-209) on broiler chicks by transcriptome profiling analysis

Decabromodiphenyl ether (BDE-209) has drawn significant attention due to its suppression of immune functions in animals and even humans. In order to explore the mechanism through which BDE-209 affects the immune system, broiler chicks were fed a diet containing various concentrations of BDE-209 (0, 0.004, 0.04, 0.4, and 4 g/kg) for 42 days. Histopathological observations of immune organs found damaged and necrotic lymphocytes in the spleen and bursa, and losses of lymphoid cells in thymic gland. The activities of catalase, glutathione, glutathione peroxidase, and superoxide dismutase in both the spleen and serum were affected by BDE-209. Obvious bioaccumulation effect was found in spleen tissues (high to 1339 ± 181.9 μg/kg). Furthermore, transcriptome sequencing analyses of the spleen identified 424 upregulated and 301 downregulated DEGs, and the cytokine-cytokine receptor interaction signal pathway was most significantly enriched based on the Kyoto Encyclopedia of Genes and Genomes database. Quantitative real-time PCR affirmed the decreased expressions of interleukin IL18, IL18R1, IL18RAP, IL21, as well as interferon gamma IFNG and tumor necrosis factor superfamily members TNFSF8, indicating significant interference to immunomodulation function and possible disease progression in inflammatory effects resulting from BDE-209 exposure. The immunotoxicity of BDE-209 may cause the suppression of immune and physiological functions of spleen cells, leading to inflammation and apoptosis and ultimately spleen atrophy.