scholarly journals The Phospholipid Profile of Mycoplasmas

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jonathan D. Kornspan ◽  
Shlomo Rottem
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Inflammatory Responses ◽  
Polar Lipids ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Ether Lipids ◽  
Mycoplasma Cell ◽  
Phospholipid Profile

Thede novosynthesized polar lipids ofMycoplasmaspecies are rather simple, comprising primarily of the acidic glycerophospholipids PG and CL. In addition, when grown in a medium containing serum, significant amounts of PC and SPM are incorporated into the mycoplasma cell membrane although these lipids are very uncommon in wall-covered bacteria. The exogenous lipids are either incorporated unchanged or the PC incorporated is modified by a deacylation-acylation enzymatic cycle to form disaturated PC. Although their small genome, in someMycoplasmaspecies, other genes involved in lipid biosynthesis were detected, resulting in the synthesis of a variety of glycolipis, phosphoglycolipids and ether lipids. We suggest that analyses and comparisons of mycoplasma polar lipids may serve as a novel and useful tool for classification. Nonetheless, to evaluate the importance of polar lipids in mycoplasma, further systematic and extensive studies on moreMycoplasmaspecies are needed. While studies are needed to elucidate the role of lipids in the mechanisms governing the interaction of mycoplasmas with host eukaryotic cells, the finding that a terminal phosphocholine containing glycolipids ofM. fermentansserves both as a major immune determinants and as a trigger of the inflammatory responses, and the findings that the fusogenicity ofM. fermentanswith host cells is markedly stimulated by lyso-ether lipids, are important steps toward understanding the molecular mechanisms ofM. fermentanspathogenicity.

scholarly journals Interaction of bacterial extracellular microvesicles with eukaryotic cells.

2021 ◽  
Vol 22 (6) ◽  
pp. 1065-1084
Author(s):  
D. S. Shlykova ◽  
V. M. Pisarev ◽  
A. M. Gaponov ◽  
A. V. Tutelyan
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Cytokines ◽  
Human Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Signal Molecules ◽  
Opportunistic Bacteria ◽  
Cytokines Secretion

Bacterial extracellular microvesicles (BMV) are formed by nonpathogenic, pathogenic and opportunistic bacteria. BMV are spherical bilayer-membrane organelles containing different cargoes: lipopolysaccharides, pathogen associated molecular patterns (PUMP), DNA, RNA, signal molecules, proteins, antibiotic resistance factors, virulence factors, toxins providing various immune response options and conducive to the survival and pathogen dissemination in the human body. BMVs secretion play an important role in the ability of microorganisms to cause various diseases. BMV are involved in biofilms formation, help bacteria to obtain nutrition in a nutrient-poor conditions, to evade the host's immune response, provide communication and surviving in a stressful environment during infection inside the host. The heterogeneity of the biogenesis mechanisms causes differences in the BMV and their characteristics including virulence rate. BMVs host cells entering is mediated by several mechanisms and helps to activate innate and adaptive immune reactions. This review focuses on interaction study of BMV with various eukaryotic cells types including neutrophils, dendritic cells, macrophages, epithelial, endothelial cells. This interaction depends on bacteria species, type of target cell and number of vesicles and can lead to different responses: non-immunogenic, pro-inflammatory, cytotoxic. Subcellular and molecular mechanisms related to the involvement of extracellular microvesicles in host's immune response modulation are presented. Stimulation of immune response is provided by increased secretion of proinflammatory cytokines and chemokines. In some cases BMV use mechanisms to evade immune surveillance: anti-inflammatory cytokines secretion, alterations of phagocytosis and chemotaxis of macrophages, increasing the proteolytic cleavage of CD14 on the macrophage surface, alterations of antigen-presenting function of dendritic cells, T-cell proliferation suppression, reducing the pro-inflammatory cytokines secretion, evasion of host-immune cells direct interactions, destruction of neutrophilic traps. These features allow bacterial cells to survive in the human body, increase their invasive potential, and reduce the excessive inflammatory reactions leading to death of the pathogen itself and life-threatening damage of tissues and organs of the host. Further studies of these mechanisms will improve existing therapeutic approaches to the infectious diseases treatment.

scholarly journals The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Feng ◽  
Yahui Feng ◽  
Liming Gu ◽  
Pengfei Liu ◽  
Jianping Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Ionizing Radiation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Antiangiogenic Therapy ◽  
Critical Role ◽  
Cellular Radiosensitivity ◽  
Normal Tissues

Ionizing radiation and radioactive materials have been widely used in industry, medicine, science and military. The efficacy of radiotherapy and adverse effects of normal tissues are closed related to cellular radiosensitivity. Molecular mechanisms underlying radiosensitivity are of significance to tumor cell radiosensitization as well as normal tissue radioprotection. 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo biosynthesis and a pterin salvage pathway. In this review we overview the role of BH4 metabolism in modulating radiosensitivity. BH4 homeostasis determines the role of NOS, affecting the production of nitric oxide (NO) and oxygen free radicals. Under conditions of oxidative stress, such as UV-radiation and ionizing radiation, BH4 availability is diminished due to its oxidation, which subsequently leads to NOS uncoupling and generation of highly oxidative free radicals. On the other hand, BH4/NOS axis facilitates vascular normalization, a process by which antiangiogenic therapy corrects structural and functional flaws of tumor blood vessels, which enhances radiotherapy efficacy. Therefore, BH4/NOS axis may serve as an angel or a devil in regulating cellular radiosensitivity. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the potential mechanisms. These advances have demonstrated that it is possible to modulate cellular radiosensitivity through BH4 metabolism.

scholarly journals Genome assembly and transcriptome analysis provide insights into the anti-schistosome mechanism of Microtus fortis

2020 ◽  
Author(s):  
Hong Li ◽  
Zhen Wang ◽  
Shumei Chai ◽  
Xiong Bai ◽  
Guohui Ding ◽  
...  
Keyword(s):  
Immune Response ◽  
Genome Assembly ◽  
Post Infection ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Inflammatory Responses ◽  
Gene Annotation ◽  
Intrinsic Resistance ◽  
Schistosome Infection ◽  
Susceptible Host

ABSTRACTMicrotus fortis (M. fortis) so far is the only mammal host that exhibits intrinsic resistance against Schistosoma japonicum infection. However, the underlying molecular mechanisms of this intrinsic resistance are not yet known. Here we performed the first de novo genome assembly of M. fortis, comprehensive gene annotation and evolution analysis. Furthermore, we compared the recovery rate of schistosome, pathological change and liver transcriptome between non-permissive host M. fortis and susceptible host mouse at different time points after Schistosome infection. We reveal that Immune response of M. fortis and mouse is different in time and type. M. fortis activates immune and inflammatory responses on the 10th days post infection, involving in multiple pathways, such as leukocyte extravasation, antibody activation (especially IgG3), Fc-gamma receptor mediated phagocytosis, and interferon signaling cascade. The strong immune responses of M. fortis in early stages of infection play important roles in preventing the development of schistosome. On the contrary, intense immune response occurred in mouse in late stages of infection (28~42 days post infection), and cannot eliminate schistosome. Infected mouse suffers severe pathological injury and continuous decrease of important functions such as cell cycle and lipid metabolism. Our findings offer new insights to the intrinsic resistance mechanism of M. fortis against schistosome infection. The genome sequence also provides bases for future studies of other important traits in M. fortis.

scholarly journals A data-driven approach to identify risk profiles and protective drugs in COVID-19

2020 ◽  
Vol 118 (1) ◽  
pp. e2016877118
Author(s):  
Pietro E. Cippà ◽  
Federica Cugnata ◽  
Paolo Ferrari ◽  
Chiara Brombin ◽  
Lorenzo Ruinelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
De Novo ◽  
Controlled Trial ◽  
Host Cells ◽  
Hospital Death ◽  
Dependency Structure ◽  
Risk Of Death ◽  
Data Driven Approach ◽  
Highly Correlated

As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease. The fragmented data collected during the initial emergency limited the possibility of investigating the effect of highly correlated covariates and of modeling the interplay between risk factors and medication. The present study is based on comprehensive monitoring of 576 COVID-19 patients. Different statistical approaches were applied to gain a comprehensive insight in terms of both the identification of risk factors and the analysis of dependency structure among clinical and demographic characteristics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2), but whether or not renin−angiotensin−aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial. The survival tree approach was applied to define a multilayer risk stratification and better profile patient survival with respect to drug regimens, showing a significant protective effect of RAASi with a reduced risk of in-hospital death. Bayesian networks were estimated, to uncover complex interrelationships and confounding effects. The results confirmed the role of RAASi in reducing the risk of death in COVID-19 patients. De novo treatment with RAASi in patients hospitalized with COVID-19 should be prospectively investigated in a randomized controlled trial to ascertain the extent of risk reduction for in-hospital death in COVID-19.

Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases

2019 ◽  
Vol 25 (12) ◽  
pp. 1345-1371 ◽  
Author(s):  
Tanzir Rafe ◽  
Parvez Ahmed Shawon ◽  
Liyad Salem ◽  
Nafij Imtiyaj Chowdhury ◽  
Farjana Kabir ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Long Run

Background:Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer’s, hypertension, stroke, cysts and cancers.Methods:This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information.Results:Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases.Conclusion:This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

Abstract 189: The Role of Spleen Tyrosine Kinase, Syk, in CD36-Toll Like Receptor Cooperative Signaling in Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Tathagat Dutta Ray ◽  
Bhama Ramkhelawon ◽  
Kathryn J Moore
Keyword(s):  
Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Sh2 Domain ◽  
Sterile Inflammation ◽  
Toll Like Receptor ◽  
Spleen Tyrosine Kinase

Atherosclerosis is characterized by chronic sterile inflammation of the artery wall in which cells of the monocyte lineage accumulate in response to the deposition of low density lipoprotein (LDL). We previously established that recognition of oxidized LDL (oxLDL) by CD36 triggers assembly of a novel Toll-like receptor heterodimer composed of TLR4 and TLR6. Here we set out to understand the molecular mechanisms of CD36/TLR4/TLR6 activation and establish how it triggers downstream signals that lead to the expression of the pro-inflammatory mediators that have been directly implicated in the deleterious effects of oxLDL and atherosclerosis progression. By confocal microscopy we demonstrate that oxLDL induces CD36, TLR4 and TLR6 co-localization in intracellular compartments, but not on the cell surface of macrophages. Notably, inhibition of oxLDL endocytosis (with Dynasore) or lysosomal maturation (with Bafilomycin A or NH4Cl) blocks CD36-TLR4-TLR6 complex formation and oxLDL-induced cytokine responses in macrophages. These data indicate that both ligand internalization and lysosomal acidification are required for assembly of a functional CD36/TLR4/TLR6 signaling complex. Notably, CD36 contains a hemi-ITIM motif in the C-terminus that is reported to interact with the spleen tyrosine kinase Syk through its SH2 domain. As Syk has recently been implicated in the trafficking of CD14 and TLR4 to the endosome in response to LPS, we investigated the role of this kinase in CD36/TLR4/TLR6 signaling. We find that Syk is required for CD36 internalization and TLR4/TLR6 heterodimerization. Using a pharmacological inhibitor, we show that inhibition of Syk activity blocks oxLDL-induced TLR4-TLR6 co-precipitation and abrogates macrophage expression of both MyD88- (IL-1b, CXCL1) and TRIF-dependent (CCL5) cytokines/chemokines. Together, our data are consistent with a key role for Syk in the trafficking of CD36 and oxLDL to the lysosome, where it coordinates the assembly of a functional TLR4-TLR6 heterodimer to initiate signaling. This model highlights the importance of CD36 as a co-receptor that orchestrates TLR4-TLR6 trafficking and assembly to initiate the detrimental inflammatory responses that promote the progression of atherosclerosis.

Role of medicinal plants against neurodegenerative diseases

2021 ◽  
Vol 22 ◽  
Author(s):  
Ritika Luthra ◽  
Arpita Roy
Keyword(s):  
Medicinal Plants ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Significant Loss ◽  
Therapeutic Interventions ◽  
Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

scholarly journals A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice

2009 ◽  
Vol 297 (6) ◽  
pp. E1276-E1282 ◽  
Author(s):  
Long Cheng ◽  
Xiao Han ◽  
Yuguang Shi
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Regulatory Role ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Acyltransferase Activity ◽  
Onset Of Diabetes ◽  
Anti Inflammatory

Platelet-activating factor (PAF) and lysophosphatidylcholine (LPC) are potent inflammatory lipids. Elevated levels of PAF and LPC are associated with the onset of diabetic retinopathy and neurodegeneration. However, the molecular mechanisms underlying such defects remain elusive. LPCAT1 is a newly reported lysophospholipid acyltransferase implicated in the anti-inflammatory response by its role in conversion of LPC to PC. Intriguingly, the LPCAT1 enzyme also catalyzes the synthesis of PAF from lyso-PAF with use of acetyl-CoA as a substrate. The present studies investigated regulatory roles of LPCAT1 in the synthesis of inflammatory lipids during the onset of diabetes. Our work shows that LPCAT1 plays an important role in the inactivation of PAF by catalyzing the synthesis of alkyl-PC, an inactivated form of PAF with use of acyl-CoA and lyso-PAF as substrates. In support of a role of LPCAT1 in anti-inflammatory responses in diabetic retinopathy, LPCAT1 is most abundantly expressed in the retina. Moreover, LPCAT1 mRNA levels and acyltransferase activity toward lyso-PAF and LPC were significantly downregulated in retina and brain tissues in response to the onset of diabetes in Ins2 Akita and db/db mice, mouse models of type 1 and type 2 diabetes, respectively. Conversely, treatment of db/db mice with rosiglitazone, an antidiabetes compound, significantly upregulated LPCAT1 mRNA levels concurrently with increased acyltransferase activity in the retina and brain. Collectively, these findings identified a novel regulatory role of LPCAT1 in catalyzing the inactivation of inflammatory lipids in the retina of diabetic mice.

Interaction of Mycoplasmas With Host Cells

2003 ◽  
Vol 83 (2) ◽  
pp. 417-432 ◽  
Author(s):  
Shlomo Rottem
Keyword(s):  
Membrane Receptors ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Dynamic Surface ◽  
Surface Molecules ◽  
A Cell ◽  
Total Lack ◽  
Diverse Interactions ◽  
Prokaryotic Microorganisms

-The mycoplasmas form a large group of prokaryotic microorganisms with over 190 species distinguished from ordinary bacteria by their small size, minute genome, and total lack of a cell wall. Owing to their limited biosynthetic capabilities, most mycoplasmas are parasites exhibiting strict host and tissue specificities. The aim of this review is to collate present knowledge on the strategies employed by mycoplasmas while interacting with their host eukaryotic cells. Prominant among these strategies is the adherence of mycoplasma to host cells, identifying the mycoplasmal adhesins as well as the mammalian membrane receptors; the invasion of mycoplasmas into host cells including studies on the role of mycoplasmal surface molecules and signaling mechanisms in the invasion; the fusion of mycoplasmas with host cells, a novel process that raises intriguing questions of how microinjection of mycoplasma components into eukaryotic cells subvert and damage the host cells. The observations of diverse interactions of mycoplasmas with cells of the immune system and their immunomodulatory effects and the discovery of genetic systems that enable mycoplasmas to rapidly change their surface antigenic composition have been important developments in mycoplasma research over the past decade, showing that mycoplasmas possess an impressive capability of maintaining a dynamic surface architecture that is antigenically and functionally versatile, contributing to the capability of the mycoplasmas to adapt to a large range of habitats and cause diseases that are often chronic in nature.

Semicarbazide-sensitive amine oxidase and kidney disease

2013 ◽  
Vol 305 (12) ◽  
pp. F1637-F1644 ◽  
Author(s):  
May Y. W. Wong ◽  
Sonia Saad ◽  
Carol Pollock ◽  
Muh Geot Wong
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Amine Oxidase ◽  
Tubular Atrophy ◽  
Progression Of Renal Disease ◽  
Protein Enzyme

With better understanding of the molecular mechanisms underpinning chronic kidney disease, the roles of inflammation and fibrosis are becoming increasingly inseparable. The progression of renal disease is characterized by pathomorphological changes that consist of early inflammatory responses followed by tubulointerstitial fibrosis, tubular atrophy, and glomerular and vascular sclerosis. Currently available therapies that reduce hypertension, proteinuria, hyperglycemia, and interruption of the renin-angiotensin-aldosterone system are at best only partially effective. Hence, there remains a need to explore agents targeting nonrenin-angiotensin-aldosterone system pathways. In this review, we discuss mechanistic aspects in the physiological and pathological role of semicarbazide-sensitive amine oxidase, a protein enzyme involved in cellular trafficking and inflammation, with respect to the kidney. We explore the evidence for the use of semicarbazide-sensitive amine oxidase inhibitors as potential agents in renal fibrosis to delay the onset and progression of chronic kidney disease.

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