scholarly journals Macrophage Proinflammatory Responses to Microorganisms and Transplanted Organs

2020 ◽  
Vol 21 (24) ◽  
pp. 9669
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Jacek Z. Kubiak ◽  
Rafik M. Ghobrial
Keyword(s):  
Tissue Repair ◽  
Surrounding Tissue ◽  
The Novel ◽  
Microbial Infection ◽  
First Line ◽  
Macrophage Response ◽  
Clinical Transplantation ◽  
Proinflammatory Responses ◽  
Inflammatory Milieu ◽  
Transplanted Organs

Tissue-resident macrophages and those conscripted from the blood/bone marrow are professional phagocytes. They play a role in tissue homeostasis, replacement, and healing, and are the first-line responders to microbial (viral, bacterial, and fungi) infections. Intrinsic ameboid-type motility allows non-resident macrophages to move to the site of inflammation or injury, where, in response to the inflammatory milieu they perform the anti-microbial and/or tissue repair functions. Depending on the need and the signaling from the surrounding tissue and other immune cells, macrophages acquire morphologically and functionally different phenotypes, which allow them to play either pro-inflammatory or anti-inflammatory functions. As such, the macrophages are also the major players in the rejection of the transplanted organs making an excellent target for the novel anti-rejection therapies in clinical transplantation. In this review, we describe some of the less covered aspects of macrophage response to microbial infection and organ transplantation.

scholarly journals Global Proteomic Analyses of Macrophage Response toMycobacterium tuberculosisInfection

2017 ◽  
Author(s):  
Valérie Poirier ◽  
Gal Av-Gay ◽  
Yossef Av-Gay
Keyword(s):  
Innate Immune ◽  
Cellular Respiration ◽  
Microbial Infection ◽  
Host Proteins ◽  
First Line ◽  
Macrophage Response ◽  
Expression Levels ◽  
The Mean ◽  
Infection Experiments

AbstractAlveolar macrophages serve as the first line of defence against microbial infection, yet provide a unique niche for the growth ofMycobacterium tuberculosis. To better understand the evasive nature of the tubercle bacilli and its molecular manifest on the macrophage response to infection, we conducted a global quantitative proteomic profile of infected macrophages. By examining four independent controlled infection experiments, we detected 42,007 peptides resulting in the characterization of 4,868 distinct proteins. Of these, we identified 845 macrophage proteins whose expression is modulated upon infection in all replicates. We showed that the macrophage’s response toM. tuberculosisinfection includes simultaneous and concerted upregulation of selected proteins. Using a number of statistical methods, we identified 27 proteins whose expression levels are significantly regulated outside of a 90% confidence interval about the mean. These host proteins represent the macrophage transcriptional, translational, and innate immune response to infection as well as its signaling capacity. The contribution of PtpA, anM. tuberculosissecreted virulence factor, modulated the expression levels of 11 host macrophage proteins, as categorized by RNA metabolism, translation, and cellular respiration.

ДИАГНОСТИКА ХРОНИЧЕСКИХ ИНДУЦИРОВАННЫХ КРАПИВНИЦ

2019 ◽  
Author(s):  
E.Yu. Borzova
Keyword(s):  
Biological Therapy ◽  
Meta Analysis ◽  
Treatment Algorithm ◽  
The Novel ◽  
First Line ◽  
Systemic Reactions ◽  
Significant Impairment ◽  
Challenge Tests ◽  
First Line Treatment

Хронические индуцированные крапивницы имеют важное социально-экономическое значение вследствие риска развития системных реакций и значительного снижения качества жизни пациентов. Диагностика хронических индуцированных крапивниц основывается на анамнестических данных и проведении провокационных тестов. Современный протокол ведения больных хронической крапивницей включает применение неседативных антигистаминных препаратов. Международные согласительные документы по лечению крапивницы рекомендуют 4-кратное увеличение суточной дозы неседативных антигистаминных препаратов при их неэффективности в стандартных дозах. Данные мета-анализа указывают на эффективность омализумаба при хронических индуцированных крапивницах. В перспективе ожидается расширение арсенала генно-инженерной биологической терапии хронических индуцированных крапивниц.Chronic inducible urticarias are characterized by the risks of systemic reactions and a significant impairment of patients quality of life. The diagnosis of chronic inducible urticarias relies on the patients history and the challenge tests. A treatment algorithm for the management of chronic inducible urticarias includes nonsedating antihistamines as a first-line treatment. The international guidelines for the management of chronic inducible urticarias recommend updosing of nonsedating antihistamines up to four fold if standard doses are not effective. The meta-analysis suggests the efficacy of omalizumab in chronic inducible urticarias. In the prospect, the novel options of biological therapy for chronic inducible urticarias are expected.

scholarly journals Powerful Bactericidal and Sterilizing Activity of a Regimen Containing PA-824, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis

2008 ◽  
Vol 52 (4) ◽  
pp. 1522-1524 ◽  
Author(s):  
Eric Nuermberger ◽  
Sandeep Tyagi ◽  
Rokeya Tasneen ◽  
Kathy N. Williams ◽  
Deepak Almeida ◽  
...  
Keyword(s):  
Murine Model ◽  
Multidrug Resistant ◽  
The Novel ◽  
Clinical Testing ◽  
First Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

ABSTRACT PA-824 is a nitroimidazo-oxazine in clinical testing for the treatment of tuberculosis. We report that the novel combination of PA-824, moxifloxacin, and pyrazinamide cured mice more rapidly than the first-line regimen of rifampin, isoniazid, and pyrazinamide. If applicable to humans, regimens containing this combination may radically shorten the treatment of multidrug-resistant tuberculosis.

Altered adipokines in obese adolescents: A cross-sectional and longitudinal analysis across the spectrum of glycemia

2021 ◽  
Author(s):  
Risa M Wolf ◽  
Andrew E Jaffe ◽  
Susana Rodriguez ◽  
Xia Lei ◽  
Dylan C. Sarver ◽  
...  
Keyword(s):  
Fibroblast Growth Factor 21 ◽  
Oral Glucose ◽  
The Novel ◽  
Cross Sectional ◽  
Obese Adolescents ◽  
Obese Youth ◽  
Glucose Tolerance Tests ◽  
Inflammatory Milieu ◽  
Related Proteins

Obesity and type 2 diabetes is rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF-21), are associated with obesity and insulin resistance in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting labs, oral glucose tolerance tests, and adipokines including: Leptin, CTRP1, CTRP9, and FGF-21. Participants completed baseline and 2-year follow-up study visits, and were categorized as lean (n=30), obese normoglycemic (ONG) (n=61), and obese hyperglycemic (OHG) (n=31) adolescents at baseline, and lean (n=8), ONG (n=18), and OHG (n=4) at follow-up. Results showed that at baseline, leptin was higher in all obese groups (p<0.001) compared to LC. FGF-21 was higher in OHG participants compared to LC (p<0.001) and ONG (p<0.001), and positively associated with fasting glucose (p<0.001), fasting insulin (p<0.001), HOMA-IR (p<0.001), and HbA1c (p=0.01). CTRP1 was higher in OHG compared to ONG (p=0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (p=0.003) and FGF21 increased in OHG (p=0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, while CTRP9 was unchanged in this cohort.

scholarly journals Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Cristina Sánchez-Quesada ◽  
Alicia López-Biedma ◽  
Estefania Toledo ◽  
José J. Gaforio
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Tissue Repair ◽  
Immune Cell ◽  
Critical Role ◽  
Virgin Olive Oil ◽  
Skin Damage ◽  
Macrophage Response ◽  
Anti Inflammatory ◽  
Minor Compounds

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

scholarly journals Expression of transcription factors (STAT 2, 3, 4, and 6, HDAC1, HDAC2) in craniopharyngioma

2021 ◽  
pp. 12
Keyword(s):  
Cyst Formation ◽  
Cell Types ◽  
Surrounding Tissue ◽  
Cytokine Signaling ◽  
High Recurrence Rate ◽  
Brain Invasion ◽  
Macrophage Response ◽  
Enhanced Expression ◽  
Critical Components ◽  
Transcription Activators

Background: Craniopharyngioma is a benign tumor of the sellar region that is typically characterized by a maldevelopment tumor with a high recurrence rate, as well as substantial morbidity and mortality in the long term. Signal transducers and transcription activators have been identified as critical components of cytokine signaling pathways that have previously been documented in craniopharyngioma-related literature. Purpose: The primary goal of this investigation is to examine transcription factor expression in craniopharyngiomas. In addition, a clinical-pathological and immunohistochemistry correlation will be sought. The current study enlisted the participation of forty patients. AdaCPs exhibited: β-catenin STAT2, STAT3, STAT6, and HDAC1 expression. While, STAT4, HDAC2, and GATA 3 were all negative. TTF1 was found in proteinaceous substances within the cyst formation (OMF). β-FGR, DPGR, TNFa, and Nrf2 were found to be associated with inflammation, OMF presence, and finger protrusion in brain surrounding tissue or brain invasion. Conclusions: Tumor recurrence was associated with increased expression of STAT3, STAT6, HDAC, β-catenin, and TNFα in WLA when compared to no recurrence. Coexpression of β-catenin, STAT2, STAT3, and STAT6 with TNFα was also shown using double fluorescence merge stains. There was no association between HDAC1 and HDAC2 coexpression and β-catenin, notably in the WLAs. Discussion: Histologically complicated features include cystic and solid components, the latter of which is made up of diverse morphological cell types. HDAC1 and HDAC2 regulate the enhanced expression of inflammatory genes during inflammation and macrophage response.

scholarly journals Maladaptive oxidative stress cascade drives type I interferon hyperactivity in TNF activated macrophages promoting necrosis in murine tuberculosis granulomas

2020 ◽  
Author(s):  
Eric Brownhill ◽  
Shivraj M. Yabaji ◽  
Vadim Zhernovkov ◽  
Oleksii S. Rukhlenko ◽  
Kerstin Seidel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Chelator ◽  
Pathogen Transmission ◽  
Type I ◽  
Macrophage Response ◽  
Intrinsic Mechanism ◽  
A Cell ◽  
Novel Therapeutic Strategies ◽  
Jnk Activation ◽  
Inflammatory Milieu

ABSTRACTTuberculosis remains a critical infectious disease world-wide. The development of novel therapeutic strategies requires greater understanding of host factors that contribute to disease susceptibility. A major unknown in TB pathogenesis is the mechanism of necrosis in TB granulomas that leads to the massive lung tissue damage and cavity formation necessary for the pathogen transmission. In humans, TB progression has been linked to hyperactivity of type I IFN (IFN-I) pathway, the primary cause of which remains elusive.We studied the mechanistic drivers of pulmonary TB progression using a unique model B6J.C3-Sst1C3HeB/Fej Krmn mice that develop human-like necrotic TB granulomas and IFN-I hyperactivity. We established that IFNβ super-induction occurred in the susceptible macrophages in response to continuous TNF stimulation in the context of a dysregulated antioxidant defense. We observed that unresolving oxidative stress amplified the induction of IFNβ through JNK activation and induced the Integrated Stress Response via PKR activation as a compensatory pathway. Subsequently, PKR amplifies IFNβ upregulation, forming a positive feedback loop, maintaining the hyperinflammatory state in susceptible macrophages and leading to mitochondrial dysfunction. Thus, within the inflammatory milieu, a cell-intrinsic mechanism of chronic regulatory dysfunction and unresolved stress gradually weakens the macrophage and ultimately promotes the necrotization of TB granulomas. The aberrant macrophage response to TNF can be prevented by an iron chelator and inhibitor of lipid peroxidation, ferrostatin-1. Moreover, ferrostatin treatment increased macrophage survival and boosted bacterial control in the TNF-stimulated macrophages infected with virulent Mtb. These findings identify targets for host-directed therapeutics to interrupt necrotization in TB granulomas.

Encorafenib, binimetinib and cetuximab combined therapy for patients with BRAFV600E mutant metastatic colorectal cancer

2020 ◽  
Vol 16 (6) ◽  
pp. 161-173 ◽  
Author(s):  
Sanne CFA Huijberts ◽  
Robin MJM van Geel ◽  
Rene Bernards ◽  
Jos H Beijnen ◽  
Neeltje Steeghs
Keyword(s):  
Growth Promotion ◽  
Combined Therapy ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Current Treatment ◽  
The Novel ◽  
Efficacy And Safety ◽  
First Line ◽  
Metastatic Setting ◽  
Mitogen Activated Protein

Approximately 10–15% of colorectal cancers (CRCs) harbor an activating BRAF mutation, leading to tumor growth promotion by activation of the mitogen-activated protein kinases pathway. BRAFV600E mutations are prognostic for treatment failure after first-line systemic therapy in the metastatic setting. In contrast to the efficacy of combined BRAF and MEK inhibition in melanoma, BRAFV600E mutant CRC is intrinsically unresponsive due to upregulation of HER/EGFR. However, combining the EGFR inhibitor cetuximab, the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib improves overall survival. This review discusses the current treatment field for patients with BRAFV600E mutant metastatic CRC and summarizes the pharmacology, efficacy and safety of the novel doublet and triplet therapies consisting of encorafenib and cetuximab with or without binimetinib.

scholarly journals EGFR-Mutant Lung Adenocarcinomas Treated First-Line with the Novel EGFR Inhibitor, XL647, Can Subsequently Retain Moderate Sensitivity to Erlotinib

2012 ◽  
Vol 7 (2) ◽  
pp. 434-442 ◽  
Author(s):  
Juliann Chmielecki ◽  
M. Catherine Pietanza ◽  
Dana Aftab ◽  
Ronglai Shen ◽  
Zhiguo Zhao ◽  
...  
Keyword(s):  
The Novel ◽  
Egfr Inhibitor ◽  
First Line ◽  
Moderate Sensitivity ◽  
Egfr Mutant ◽  
Lung Adenocarcinomas

scholarly journals A Practical Approach for Residency Programs to Revive Graduate Medical Education during the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: A Battle Proven Concept

2021 ◽  
Vol 8 (3) ◽  
pp. 01-02
Author(s):  
Yousif Al-Saiegh
Keyword(s):  
Internal Medicine ◽  
Medical Education ◽  
Graduate Medical Education ◽  
Educational Environment ◽  
Internal Medicine Residency ◽  
The Novel ◽  
First Line ◽  
Residency Programs ◽  
Novel Coronavirus ◽  
Continued Medical Education

The Novel Coronavirus Disease 2019 (COVID-19) Pandemic impacted the educational environment of Internal Medicine residency programs tremendously, shifting the focus from continued medical education to being the first line of defense while taking care of patients with COVID-19. Our article discusses an approach to reestablish medical education in the midst of a pandemic.

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