scholarly journals Concurrent cavitary pulmonary tuberculosisand COVID-19 pneumonia with in vitro immune cell anergy:a case report.

2020 ◽  
Author(s):  
Maria Musso ◽  
Francesco Di Gennaro ◽  
Gina Gualano ◽  
Silvia Mosti ◽  
Carlotta Cerva ◽  
...  
Keyword(s):  
Immune Cell ◽  
Point Of View ◽  
Control Measures ◽  
Chest Imaging ◽  
Double Burden ◽  
Pulmonary Tb ◽  
Affect Control ◽  
Essential Services ◽  
Cell Anergy

Abstract Tuberculosis (TB) is top infectious disease killer caused by a single organismresponsible for 1.5 million deaths in 2018. Both COVID 19 and the pandemic responseare risking to affect control measures for TB and continuity of essential services forpeople affected by this infection in western countries and even more in developingcountries. Knowledges about concomitant pulmonary TB and COVID-19 are extremelylimited. The double burden of these two diseases can have devastating effects. Herewe describe from both the clinical and the immunological point of view a case of apatient with in vitro immune cell anergy affected by bilateral cavitary pulmonary TB andsubsequent COVID-19-associated pneumonia with a worst outcome. COVID-19 can bea precipitating factor in TB respiratory failure and, during ongoing SARS COV 2 pandemic, clinicians must be aware of this possible coinfection in differential diagnosisof patients with active TB and new or worsening chest imaging

scholarly journals Concurrent cavitary pulmonary tuberculosis and COVID-19 pneumonia with in vitro immune cell anergy

Infection ◽  
2021 ◽  
Author(s):  
Maria Musso ◽  
Francesco Di Gennaro ◽  
Gina Gualano ◽  
Silvia Mosti ◽  
Carlotta Cerva ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Immune Cell ◽  
Cell Anergy

scholarly journals The J2-Immortalized Murine Macrophage Cell Line Displays Phenotypical and Metabolic Features of Primary BMDMs in Their M1 and M2 Polarization State

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5478
Author(s):  
Iolanda Spera ◽  
Ricardo Sánchez-Rodríguez ◽  
Maria Favia ◽  
Alessio Menga ◽  
Francisca C. Venegas ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Activation ◽  
Immune Cell ◽  
Polarization State ◽  
Point Of View ◽  
Suitable Model ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Functional Features

Macrophages are immune cells that are important for the development of the defensive front line of the innate immune system. Following signal recognition, macrophages undergo activation toward specific functional states, consisting not only in the acquisition of specific features but also of peculiar metabolic programs associated with each function. For these reasons, macrophages are often isolated from mice to perform cellular assays to study the mechanisms mediating immune cell activation. This requires expensive and time-consuming breeding and housing of mice strains. To overcome this issue, we analyzed an in-house J2-generated immortalized macrophage cell line from BMDMs, both from a functional and metabolic point of view. By assaying the intracellular and extracellular metabolism coupled with the phenotypic features of immortalized versus primary BMDMs, we concluded that classically and alternatively immortalized macrophages display similar phenotypical, metabolic and functional features compared to primary cells polarized in the same way. Our study validates the use of this immortalized cell line as a suitable model with which to evaluate in vitro how perturbations can influence the phenotypical and functional features of murine macrophages.

Enzyme Promiscuous Activity: How to Define it and its Evolutionary Aspects

2020 ◽  
Vol 27 (5) ◽  
pp. 400-410
Author(s):  
Valentina De Luca ◽  
Luigi Mandrich
Keyword(s):  
Gene Evolution ◽  
Sequence Divergence ◽  
High Specificity ◽  
Industrial Applications ◽  
Point Of View ◽  
Enzyme Promiscuity ◽  
Primary Activity ◽  
Starting Point ◽  
Main Activity

: Enzymes are among the most studied biological molecules because better understanding enzymes structure and activity will shed more light on their biological processes and regulation; from a biotechnological point of view there are many examples of enzymes used with the aim to obtain new products and/or to make industrial processes less invasive towards the environment. Enzymes are known for their high specificity in the recognition of a substrate but considering the particular features of an increasing number of enzymes this is not completely true, in fact, many enzymes are active on different substrates: this ability is called enzyme promiscuity. Usually, promiscuous activities have significantly lower kinetic parameters than to that of primary activity, but they have a crucial role in gene evolution. It is accepted that gene duplication followed by sequence divergence is considered a key evolutionary mechanism to generate new enzyme functions. In this way, promiscuous activities are the starting point to increase a secondary activity in the main activity and then get a new enzyme. The primary activity can be lost or reduced to a promiscuous activity. In this review we describe the differences between substrate and enzyme promiscuity, and its rule in gene evolution. From a practical point of view the knowledge of promiscuity can facilitate the in vitro progress of proteins engineering, both for biomedical and industrial applications. In particular, we report cases regarding esterases, phosphotriesterases and cytochrome P450.

Insecticidal Active Rotenoids from Plant Parts and Callus Culture of Medicago sativa L. from a Semiarid Region of India (Rajasthan)

2020 ◽  
Vol 16 (6) ◽  
pp. 937-941
Author(s):  
Sharad Vats ◽  
Preeti Mehra
Keyword(s):  
Medicago Sativa ◽  
Callus Culture ◽  
Point Of View ◽  
Semiarid Region ◽  
Disease Vectors ◽  
Vector Borne Diseases ◽  
Plant Parts ◽  
Resistant Varieties ◽  
Medicago Sativa L

Background: Vector-borne diseases are quite prevalent globally and are one of the major causes of deaths due to infectious diseases. There is an availability of synthetic insecticides, however, their excessive and indiscriminate use have resulted in the emergence of resistant varieties of insects. Thus, a search for novel biopesticide has become inevitable. Methods: Rotenoids were isolated and identified from different parts of Medicago sativa L. This group of metabolites was also identified in the callus culture, and the rotenoid content was monitored during subculturing for a period of 10 months. Enhancement of the rotenoid content was evaluated by feeding precursors in a tissue culture medium. Results: Four rotenoids (elliptone, deguelin, rotenone and Dehydrorotenone) were identified, which were confirmed using spectral and chromatographic techniques. The maximum rotenoid content was found in the seeds (0.33±0.01%), followed by roots (0.31±0.01%) and minimum in the aerial parts (0.20±0.05%). A gradual decrease in the rotenoid content was observed with the ageing of subcultured tissue maintained for 10 months. The production of rotenoids was enhanced up to 2 folds in the callus culture using amino acids, Phenylalanine and Methionine as precursors as compared to the control. The LC50 value of the rotenoids was found to be 91 ppm and 162 ppm against disease vectors of malaria and Dracunculiasis, respectively. Conclusion: The study projects M. sativa as a novel source of biopesticide against the disease vectors of malaria and Dracunculiasis. The use of precursors to enhance the rotenoid content in vitro can be an effective venture from a commercial point of view.

Effects of Weed Control in Established Alfalfa (Medicago sativa) on Forage Yield and Quality

Weed Science ◽  
1987 ◽  
Vol 35 (4) ◽  
pp. 564-567 ◽  
Author(s):  
Dennis R. Cosgrove ◽  
Michael Barrett
Keyword(s):  
Medicago Sativa ◽  
Weed Control ◽  
Stand Density ◽  
Forage Yield ◽  
Control Measures ◽  
Acid Detergent Fiber ◽  
Yield And Quality ◽  
Herbicide Treatments ◽  
Forage Yields

The effects of weed control measures in established alfalfa (Medicago sativaL.) on forage yield and quality were investigated at three sites with varying alfalfa densities and weed populations. Herbicide treatments were 0.56 and 1.12 kg/ha metribuzin [4-amino-6-(1,1-dimethylethyl)-3-(methylthio)-1,2,4-triazin-5(4H)-one] applied in fall or spring, respectively, 1.68 kg/ha pronamide [3,5-dichloro (N-1,1-dimethyl-2-propynyl)benzamide] applied in fall, and combinations of these treatments. First-harvest forage yields (weeds plus alfalfa) were either reduced or unchanged by herbicide treatments. Total forage yield was not altered by the herbicide treatments, but first-harvest and total alfalfa yield as well as first-harvest forage protein content were increased by several treatments, depending on stand density and weed pressure. Little effect was observed on in vitro digestible dry matter or acid detergent fiber content.

scholarly journals Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Wilmer Cuervo ◽  
Lorraine M. Sordillo ◽  
Angel Abuelo
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Dairy Calves ◽  
Lymphocyte Function ◽  
Newborn Calves ◽  
Ifn Γ ◽  
The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

scholarly journals Potential of Probiotic Frozen Blackcurrant Products: Consumer Preference, Physicochemical Characterization, and Cell Viability

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 792
Author(s):  
Kati Väkeväinen ◽  
Noora Rinkinen ◽  
Roosa-Maria Willman ◽  
Jenni Lappi ◽  
Kaisa Raninen ◽  
...  
Keyword(s):  
Storage Time ◽  
Physicochemical Characterization ◽  
Consumer Preference ◽  
Nutritional Composition ◽  
Point Of View ◽  
Raw Material ◽  
Frozen Food ◽  
High Viability ◽  
Food Applications

Blackcurrant is a healthy, affordable, and traditionally gardened berry that, thus far, has been underused in food applications. From the consumers’ point of view, the acidic taste of blackcurrants is a challenge; therefore, these berries have mainly been utilized for sugary juice production. This research study aimed to develop a frozen vegan blackcurrant product with pleasant sensory properties and potential probiotic function. A candidate probiotic, Lactoplantibacillus plantarum Q823, was used in the manufacturing process. The physicochemical properties, nutritional composition, and consumer preference for the developed product were assessed, as was the viability of L. plantarum Q823 during storage time and in an in vitro gastrointestinal model. Consumers (n = 71) perceived the developed product to be pleasant. L. plantarum Q823 had high viability counts (log colony forming units (cfu) g−1 7.0 ± 0.38) in the final product, although the viability of L. plantarum Q823 during storage time needs to be enhanced to obtain a probiotic product. Thus, within an optimized formulation, blackcurrant berries represent a potential raw material for functional frozen food products.

scholarly journals DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii63-ii63
Author(s):  
Lakshmi Bollu ◽  
Derek Wainwright ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Time Course ◽  
Immune Cell ◽  
Enzyme Inhibitors ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Specific Protein ◽  
Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

scholarly journals Structures of mouse and human GITR–GITRL complexes reveal unique TNF superfamily interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Wang ◽  
Bryant Chau ◽  
Sean M. West ◽  
Christopher R. Kimberlin ◽  
Fei Cao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Signaling ◽  
Tumor Necrosis ◽  
Immune Cell ◽  
Linear Chain ◽  
Tumor Necrosis Factor Receptor ◽  
Higher Order ◽  
Membrane Structures ◽  
Receptor Interface

AbstractGlucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.

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