scholarly journals Towards an ecological definition of sepsis: a viewpoint

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael Bauer ◽  
Manu Shankar-Hari ◽  
Daniel O. Thomas-Rüddel ◽  
Reinhard Wetzker
Keyword(s):  
Stress Response ◽  
Response Pattern ◽  
Energy State ◽  
Treatment Options ◽  
Stress Factors ◽  
Source Control ◽  
Adaptive Responses ◽  
General Stress Response ◽  
Lung Failure ◽  
Definition Of

AbstractIn critically ill patients with sepsis, there is a grave lack of effective treatment options to address the illness-defining inappropriate host response. Currently, treatment is limited to source control and supportive care, albeit with imminent approval of immune modulating drugs for COVID-19-associated lung failure the potential of host-directed strategies appears on the horizon. We suggest expanding the concept of sepsis by incorporating infectious stress within the general stress response of the cell to define sepsis as an illness state characterized by allostatic overload and failing adaptive responses along with biotic (pathogen) and abiotic (e.g., malnutrition) environmental stress factors. This would allow conceptualizing the failing organismic responses to pathogens in sepsis with an ancient response pattern depending on the energy state of cells and organs towards other environmental stressors in general. Hence, the present review aims to decipher the heuristic value of a biological definition of sepsis as a failing stress response. These considerations may motivate a better understanding of the processes underlying “host defense failure” on the organismic, organ, cell and molecular levels.

scholarly journals ORA47 is a transcriptional regulator of a general stress response hub

2021 ◽  
Author(s):  
Liping Zeng ◽  
Hao Chen ◽  
Yaqi Wang ◽  
Derrick Hicks ◽  
Haiyan Ke ◽  
...  
Keyword(s):  
Stress Response ◽  
Protein S ◽  
Regulatory Proteins ◽  
Adaptive Responses ◽  
Genetic Studies ◽  
General Stress Response ◽  
Calmodulin Binding ◽  
General Stress ◽  
Cellular Events ◽  
Inducible Protein

Transcriptional regulators of general stress response (GSR) reprogram expression of selected genes to transduce informational signals into cellular events, ultimately manifested in plant's ability to cope with environmental challenges. Identification of the core GSR regulatory proteins will uncover the principal modules and their mode of action in the establishment of adaptive responses. To define the GSR regulatory components, we employed a yeast-one-hybrid assay to identify the protein(s) that binds to the previously established functional GSR motif, coined Rapid Stress Response Element (RSRE). This led to the isolation of ORA47 (octadecanoid-responsive AP2/ERF-domain transcription factor 47), a Methyl jasmonate (MeJA) inducible protein. Subsequently, the ORA47 transcriptional activity was confirmed using RSRE-driven Luciferase (LUC) activity assay performed in the ORA47 loss- and gain-of-function lines introgressed into the 4xRSRE::Luc background. In addition, the prime contribution of CALMODULIN-BINDING TRANSCRIPTIONAL ACTIVATOR3 (CAMTA3) protein in induction of RSRE was reaffirmed by genetic studies. Moreover, exogenous application of MeJA led to enhanced levels of ORA47 and CAMTA3 transcripts, and the induction of RSRE::LUC activity. Metabolic analyses illustrated the reciprocal functional inputs of ORA47 and CAMTA3 in increasing JA levels. Lastly, transient assays identified JASMONATE ZIM-domain1 (JAZ1) as a repressor of RSRE::LUC activity.

scholarly journals Red Light Activates the σB-Mediated General Stress Response of Bacillus subtilis via the Energy Branch of the Upstream Signaling Cascade

2009 ◽  
Vol 192 (3) ◽  
pp. 755-762 ◽  
Author(s):  
Marcela Ávila-Pérez ◽  
Jeroen B. van der Steen ◽  
Remco Kort ◽  
Klaas J. Hellingwerf
Keyword(s):  
Bacillus Subtilis ◽  
Stress Response ◽  
Red Light ◽  
Light Response ◽  
Stress Factors ◽  
Signaling Cascade ◽  
Phosphatase Domain ◽  
General Stress Response ◽  
General Stress ◽  
Light Effects

ABSTRACT The σB-dependent general stress response in the common soil bacterium Bacillus subtilis can be elicited by a range of stress factors, such as starvation or an ethanol, salt, or heat shock, via a complex upstream signaling cascade. Additionally, σB can be activated by blue light via the phototropin homologue YtvA, a component of the environmental branch of the signaling cascade. Here we use a reporter-gene fusion to show that σB can also be activated by red light via the energy branch of its upstream signaling cascade. Deletion mutagenesis and homologous overproduction experiments indicate that the RsbP protein (composed of an N-terminal Per-ARNT-Sim [PAS] domain and a C-terminal PP2C-type phosphatase domain) is involved in the red light response. This second light input pathway functions complementarily to YtvA; it shows broader spectral sensitivity but requires higher light intensities. These results are confirmed by transcriptome analyses, which show that both light effects result in upregulation of the σB regulon, with minimal activation of other responses.

Rash and Mucositis Associated With Mycoplasma pneumoniae and Chlamydophila pneumoniae: A Recurrence of MIRM?

2020 ◽  
Author(s):  
Danielle Brazel ◽  
Brooke Kulp ◽  
Geoanna Bautista ◽  
Andrew Bonwit
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Treatment Options ◽  
Specific Treatment ◽  
Corticosteroid Treatment ◽  
Stevens Johnson Syndrome ◽  
First Case ◽  
Johnson Syndrome ◽  
Vesicular Rash ◽  
Recurrent Aphthous Ulcers ◽  
Definition Of

Abstract Introduction A new concept has come to light recently, that is, Mycoplasma-induced rash and mucositis (MIRM). Here, we report the first case of recurrent rash, mucositis, and conjunctivitis involving Mycoplasma pneumoniae and C. pneumoniae that fits under the criteria of what is currently defined as MIRM. Case Presentation A patient aged 12 years with a history of recurrent aphthous ulcers presented in 2013 with worsening oral lesions, conjunctivitis, and vesicular rash. Her respiratory polymerase chain reaction (PCR) panel was positive for M. pneumoniae. She was diagnosed with Stevens-Johnson syndrome (SJS) secondary to M. pneumoniae and treated with a macrolide, acyclovir, and intravenous immunoglobulin (IVIG). The same patient returned 3 years later with an identical constellation of symptoms, at which time her PCR was positive for C. pneumoniae. In addition to IVIG and a macrolide, a corticosteroid treatment was administered. Discussion Here, we present the case of a pediatric patient with a recurrence of mucocutaneous disease that is more consistent with MIRM than the proposed SJS or erythema multiforme (EM) documented via histology. Our patient’s symptoms were controlled with azithromycin and IVIG and, in the second episode, with corticosteroids as well. This case adds to that of Mayor-Ibarguren et al, providing further evidence that C. pneumonia may also be a trigger for MIRM. Patients will benefit from expanding the definition of MIRM, as the pathogenesis differs from SJS and EM and could result in more specific treatment options.

scholarly journals Mtl1 Is Required to Activate General Stress Response through Tor1 and Ras2 Inhibition under Conditions of Glucose Starvation and Oxidative Stress

2010 ◽  
Vol 285 (25) ◽  
pp. 19521-19531 ◽  
Author(s):  
Mima Ivanova Petkova ◽  
Nuria Pujol-Carrion ◽  
Javier Arroyo ◽  
Jesús García-Cantalejo ◽  
Maria Angeles de la Torre-Ruiz
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Glucose Starvation ◽  
General Stress Response ◽  
General Stress ◽  
And Oxidative Stress

scholarly journals Mechanistic Inferences from Clinical Reports of SARS-CoV-2

2020 ◽  
Author(s):  
Meagan M Jenkins ◽  
Tyler R McCaw ◽  
Paul A Goepfert
Keyword(s):  
Randomized Clinical Trials ◽  
Severe Disease ◽  
Treatment Options ◽  
Management Strategies ◽  
Type I ◽  
Interferon Signaling ◽  
Adaptive Responses ◽  
Initial Clinical Trial ◽  
Inflammatory State ◽  
Clinical Trial Results

SARS-CoV-2 was identified as the causative pathogen in an outbreak of viral pneumonia cases originating in Wuhan, China, with an ensuing rapid global spread that led it to be declared a pandemic by the WHO on March 11, 2020. Given the threat to public health posed by sequelae of SARS-CoV-2 infection, the literature surrounding patient presentation in severe and non-severe cases, transmission rates and routes, management strategies, and initial clinical trial results have become available at an unprecedented pace. In this review we collate current clinical and immunologic reports, comparing these to reports of previous coronaviruses to identify mechanisms driving progression to severe disease in some patients. In brief, we propose a model wherein dysregulated type I interferon signaling leads to aberrant recruitment and accumulation of innate immune lineages in the lung, impairing establishment of productive adaptive responses, and permitting a pathologic pro-inflammatory state. Finally, we extend these findings to suggest possible treatment options that may merit investigation in randomized clinical trials.

scholarly journals Rare Treatments for Rare Dyslipidemias: New Perspectives in the Treatment of Homozygous Familial Hypercholesterolemia (HoFH) and Familial Chylomicronemia Syndrome (FCS)

2021 ◽  
Vol 23 (11) ◽  
Author(s):  
Laura D’Erasmo ◽  
Simone Bini ◽  
Marcello Arca
Keyword(s):  
Familial Hypercholesterolemia ◽  
Treatment Options ◽  
New Drugs ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Published Evidence ◽  
Novel Drugs ◽  
Life Threatening ◽  
History Of ◽  
Definition Of

Abstract Purpose of Review This review aims to summarize the most recent published literature concerning lomitapide and volanesorsen that are approved for the use in HoFH and FCS patients, respectively. Moreover, it will briefly revise the published evidence on novel, non-approved treatments that are under evaluation for the management of these rare forms of dyslipidemias Recent Findings The definition of rare dyslipidemias identifies a large number of severe disorders of lipid metabolism of genetic origin. Among them were homozygous familial hypercholesterolemia (HoFH) (OMIM #143890) and familial chylomicronemia syndrome (FCS) (OMIM #238600), which are characterized by a markedly impaired cholesterol- and triglyceride-containing lipoproteins metabolism. They are being particularly associated with poor health outcomes and quality of life. Considering the severity of these diseases, common lipid-lowering drugs are often ineffective or do not allow to achieve the recommended lipid targets to prevent the development of complications. Nowadays, several new drugs have been found to effectively treat HoFH and FCS with an acceptable safety profile. Summary Treating patients with HoFH and FCS remains very challenging. However, novel treatment options are emerging and might be considered in addition to conventional therapy for managing these diseases. These novel drugs will possibly change the natural history of these two rare and life-threatening diseases.

scholarly journals Computational Analysis of the Pulmonary Arteries in Congenital Heart Disease: A Review of the Methods and Results

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
M. Conijn ◽  
G. J. Krings
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Boundary Conditions ◽  
Congenital Heart ◽  
Treatment Options ◽  
Pulmonary Arteries ◽  
Original Research ◽  
Numerical Studies ◽  
Computational Fluid Dynamics Cfd ◽  
Definition Of

With the help of computational fluid dynamics (CFD), hemodynamics of the pulmonary arteries (PA’s) can be studied in detail and varying physiological circumstances and treatment options can be simulated. This offers the opportunity to improve the diagnostics and treatment of PA stenosis in biventricular congenital heart disease (CHD). The aim of this review was to evaluate the methods of computational studies for PA’s in biventricular CHD and the level of validation of the numerical outcomes. A total of 34 original research papers were selected. The literature showed a great variety in the used methods for (re) construction of the geometry as well as definition of the boundary conditions and numerical setup. There were 10 different methods identified to define inlet boundary conditions and 17 for outlet boundary conditions. A total of nine papers verified their CFD outcomes by comparing results to clinical data or by an experimental mock loop. The diversity in used methods and the low level of validation of the outcomes result in uncertainties regarding the reliability of numerical studies. This limits the current clinical utility of CFD for the study of PA flow in CHD. Standardization and validation of the methods are therefore recommended.

scholarly journals Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa)

2021 ◽  
Vol 16 (1) ◽  
pp. 1111-1121
Author(s):  
Yongqun Zhu ◽  
Qiuxu Liu ◽  
Wenzhi Xu ◽  
Li Yao ◽  
Xie Wang ◽  
...  
Keyword(s):  
Drought Stress ◽  
Stress Response ◽  
Protein Transport ◽  
Target Genes ◽  
Comparison Group ◽  
Stress Factors ◽  
Leguminous Plant ◽  
Vicia Sativa ◽  
Common Vetch ◽  
Drought Treatment

Abstract Drought is among the most important natural disasters with severe effects on animals and plants. MicroRNAs are a class of noncoding RNAs that play a crucial role in plant growth, development, and response to stress factors, including drought. However, the microRNAs in drought responses in common vetch (Vicia sativa), an annual herbaceous leguminous plant commonly used for forage by including it in mixed seeding during winter and spring, have not been characterized. To explore the microRNAs’ response to drought in common vetch, we sequenced 10 small RNA (sRNA) libraries by the next-generation sequencing technology. We obtained 379 known miRNAs belonging to 38 families and 47 novel miRNAs. The two groups had varying numbers of differentially expressed miRNAs: 85 in the comparison group D5 vs C5 and 38 in the comparison group D3 vs C3. Combined analysis of mRNA and miRNA in the same samples under drought treatment identified 318 different target genes of 123 miRNAs. Functional annotation of the target genes revealed that the miRNAs regulate drought-responsive genes, such as leucine-rich repeat receptor-like kinase-encoding genes (LRR-RLKs), ABC transporter G family member 1 (ABCG1), and MAG2-interacting protein 2 (MIP2). The genes were involved in various pathways, including cell wall biosynthesis, reactive oxygen removal, and protein transport. The findings in this study provide new insights into the miRNA-mediated regulatory networks of drought stress response in common vetch.

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