Biomarkers of inflammation and the etiology of sepsis

Sepsis is characterized as a life-threatening organ dysfunction syndrome that is caused by a dysregulated host response to infection. The main etiological causes of sepsis are bacterial, fungal, and viral infections. Last decades clinical and preclinical research contributed to a better understanding of pathophysiology of sepsis. The dysregulated host response in sepsis is complex, with both pathogen-related factors contributing to disease, as well as immune-cell mediated inflammatory responses that can lead to adverse outcomes in early or advanced stages of disease. Due to its heterogenous nature, clinical diagnosis remains challenging and sepsis-specific treatment options are still lacking. Classification and early identification of patient subgroups may aid clinical decisions and improve outcome in sepsis patients. The initial clinical presentation is rather similar in sepsis of different etiologies, however, inflammatory profiles may be able to distinguish between different etiologies of infections. In this review, we summarize the role and the discriminating potency of host-derived inflammatory biomarkers in the context of the main etiological types of sepsis.

Download Full-text

Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.563126 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wei Wang ◽

Ni Yang ◽

Ri Wen ◽

Chun-Feng Liu ◽

Tie-Ning Zhang

Keyword(s):

Host Response ◽

Noncoding Rna ◽

Therapeutic Potential ◽

Noncoding Rnas ◽

Specific Treatment ◽

Kidney Injury ◽

Biological Processes ◽

Immune Functions ◽

Life Threatening ◽

Organ Dysfunctions

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.

Download Full-text

SARS-CoV-2 in Pregnancy: Fitting Into the Existing Viral Repertoire

Frontiers in Global Women's Health ◽

10.3389/fgwh.2021.647836 ◽

2021 ◽

Vol 2 ◽

Author(s):

Roopali Rajput ◽

Jitender Sharma

Keyword(s):

Immune System ◽

Viral Infection ◽

Pregnant Women ◽

Preterm Labor ◽

Viral Infections ◽

Treatment Options ◽

Adverse Outcomes ◽

Fetal Health ◽

Fetal Protection ◽

In Pregnancy

The risk of viral infection during pregnancy is well-documented; however, the intervention modalities that in practice enable maternal-fetal protection are restricted by limited understanding. This becomes all the more challenging during pandemics. During many different epidemic and pandemic viral outbreaks, worse outcomes (fetal abnormalities, mortality, preterm labor, etc.) seem to affect pregnant women than what has been evident when compared to non-pregnant women. The condition of pregnancy, which is widely understood as “immunosuppressed,” needs to be re-understood in terms of the way the immune system works during such a state. The immune system gets transformed to accommodate and facilitate fetal growth. The interference of such supportive conversion by viral infection and the risk of co-infection lead to adverse fetal outcomes. Hence, it is crucial to understand the risk and impact of potent viral infections likely to be encountered during pregnancy. In the present article, we review the effects imposed by previously established and recently emerging/re-emerging viral infections on maternal and fetal health. Such understanding is important in devising strategies for better preparedness and knowing the treatment options available to mitigate the relevant adverse outcomes.

Download Full-text

Balancing Precision vs. Cohort Transcriptomic Analysis of Acute and Recovery Phase of Viral Bronchiolitis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00440.2020 ◽

2021 ◽

Author(s):

Ruchir Gupta ◽

Mara L Leimanis ◽

Marie Adams ◽

Andre S Bachmann ◽

Katie L. Uhl ◽

...

Keyword(s):

Cell Activation ◽

Viral Infections ◽

Immune Cell ◽

Healthcare Delivery ◽

Recovery Phase ◽

Adverse Outcomes ◽

Cytokine Signaling ◽

Cytokine Activation ◽

Biological Responses ◽

Syncytial Virus

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor anti-viral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved healthcare delivery. A cohort of PAXGene RNAseq of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus (RSV) were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Severe bronchiolitis patients had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand totality of mechanisms of adverse outcomes in viral bronchiolitis.

Download Full-text

Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence

Journal of Aging Research ◽

10.4061/2011/951403 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 14

Author(s):

Dimitrios Adamis ◽

David Meagher

Keyword(s):

Inflammatory Responses ◽

Well Being ◽

Adverse Outcomes ◽

Current Evidence ◽

Related Factors ◽

Future Studies ◽

Medically Ill ◽

Therapeutic Trials ◽

Hormone Administration ◽

Igf I

Delirium is a frequent complication in medically ill elderly patients that is associated with serious adverse outcomes including increased mortality. Delirium risk is linked to older age, dementia, and illness that involves activation of inflammatory responses. IGF-I is increasingly postulated as a key link between environmental influences on body metabolism with a range of neuronal activities and has been described as themaster regulatorof the connection between brain and bodily well-being. The relationships between IGF-I and ageing, cognitive impairment and inflammatory illness further support a possible role in delirium pathogenesis. Five studies of IGF-I in delirium were identified by a systematic review. These conflicting findings, with three of the five studies indicating an association between IGF-1 and delirium occurrence, may relate to the considerable methodological differences in these studies. The relevance of IGF-I and related factors to delirium pathogenesis can be clarified by future studies which account for these issues and other confounding factors. Such work can inform therapeutic trials of IGF-I and/or growth hormone administration.

Download Full-text

COVID-19: molecular pathophysiology, genetic evolution and prospective therapeutics—a review

Archives of Microbiology ◽

10.1007/s00203-021-02183-z ◽

2021 ◽

Author(s):

C. T. Dhanya Raj ◽

Dinesh Kumar Kandaswamy ◽

Ravi Chandra Sekhara Reddy Danduga ◽

Raju Rajasabapathy ◽

Rathinam Arthur James

Keyword(s):

Drug Targets ◽

Continuous Monitoring ◽

Drug Repositioning ◽

Therapeutic Option ◽

Treatment Options ◽

Specific Treatment ◽

Medical Emergency ◽

Life Threatening ◽

Molecular Machinery ◽

Molecular Pathophysiology

AbstractThe Covid-19 pandemic is highly contagious and has spread rapidly across the globe. To date there have been no specific treatment options available for this life-threatening disease. During this medical emergency, target-based drug repositioning/repurposing with a continuous monitoring and recording of results is an effective method for the treatment and drug discovery. This review summarizes the recent findings on COVID-19, its genomic organization, molecular evolution through phylogenetic analysis and has recapitulated the drug targets by analyzing the viral molecular machinery as drug targets and repurposing of most frequently used drugs worldwide and their therapeutic applications in COVID-19. Data from solidarity trials have shown that the treatment with Chloroquine, hydroxychloroquine and lopinavir-ritonavir had no effect in reducing the mortality rate and also had adverse side effects. Remdesivir, Favipiravir and Ribavirin might be a safer therapeutic option for COVID-19. Recent clinical trial has revealed that dexamethasone and convalescent plasma treatment can reduce mortality in patients with severe forms of COVID-19.

Download Full-text

Hypoxia-Inducible Factor 1 Alpha Is Dispensable for Host Defense of Group B Streptococcus Colonization and Infection

Journal of Innate Immunity ◽

10.1159/000515739 ◽

2021 ◽

pp. 1-13

Author(s):

Gregory R. Lum ◽

Vicki Mercado ◽

Diede van Ens ◽

Victor Nizet ◽

Jacqueline M. Kimmey ◽

...

Keyword(s):

Host Response ◽

Immune Cell ◽

Systemic Disease ◽

Treatment Options ◽

Hypoxia Inducible Factor ◽

Immune Defense ◽

Hypoxia Inducible Factor 1 ◽

Group B

Group B <i>Streptococcus</i> (GBS) is a leading cause of neonatal morbidity and mortality, and the primary source of exposure is the maternal vagina. Intrapartum antibiotic prophylaxis for GBS-positive mothers has reduced the incidence of GBS early-onset disease, however, potential long-lasting influence of an antibiotic-altered neonatal microbiota, and the frequent clinical sequelae in survivors of invasive GBS infection, compels alternative treatment options for GBS. Here, we examined the role of transcription factor hypoxia-inducible factor 1 alpha (HIF-1α), widely recognized as a regulator of immune activation during infection, in the host response to GBS. Given the importance of endogenous HIF-1α for innate immune defense, and the potential utility of HIF-1α stabilization in promoting bacterial clearance, we hypothesized that HIF-1α could play an important role in coordinating host responses to GBS in colonization and systemic disease. Counter to our hypothesis, we found that GBS infection did not induce HIF-1α expression in vaginal epithelial cells or murine macrophages, nor did HIF-1α deficiency alter GBS colonization or pathogenesis in vivo. Furthermore, pharmacological enhancement of HIF-1α did not improve control of GBS in pathogenesis and colonization models, while displaying inhibitory effects in vaginal epithelial cytokines and immune cell killing in vitro. Taken together, we conclude that HIF-1α is not a prominent aspect of the host response to GBS colonization or invasive disease, and its pharmacological modulation is unlikely to provide significant benefit against this important neonatal pathogen.

Download Full-text

Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors

Scientific Reports ◽

10.1038/s41598-021-82221-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fengju Chen ◽

Yiqun Zhang ◽

Richard Sucgang ◽

Sasirekha Ramani ◽

David Corry ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Host Response ◽

Viral Infections ◽

Immune Cell ◽

Human Cancer ◽

Meta Analysis ◽

Model Systems ◽

Host Responses ◽

Transcriptional Responses ◽

Wide Range

AbstractA deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.

Download Full-text

Targeting the “Cytokine Storm” for Therapeutic Benefit

Clinical and Vaccine Immunology ◽

10.1128/cvi.00636-12 ◽

2013 ◽

Vol 20 (3) ◽

pp. 319-327 ◽

Cited By ~ 135

Author(s):

Riccardo V. D'Elia ◽

Kate Harrison ◽

Petra C. Oyston ◽

Roman A. Lukaszewski ◽

Graeme C. Clark

Keyword(s):

Immune Responses ◽

Host Response ◽

Inflammatory Responses ◽

Therapeutic Benefit ◽

Adaptive Responses ◽

First Line ◽

Diverse Range ◽

Content Type ◽

Life Threatening ◽

Significant Pathology

ABSTRACTInflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacteriumFrancisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.

Download Full-text

PCSK9: A Potential Therapeutic Target for Sepsis

Journal of Immunology Research ◽

10.1155/2020/2687692 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuan Yuan ◽

Wei Wu ◽

Shanshan Sun ◽

Yi Zhang ◽

Zhi Chen

Keyword(s):

Host Response ◽

Inflammatory Responses ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Lipid Uptake ◽

Low Density Lipoprotein Cholesterol ◽

Life Threatening

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is often upregulated in the presence of sepsis and infectious diseases. In sepsis, PCSK9 degraded the low-density lipoprotein cholesterol (LDL) receptors (LDL-R) of the hepatocytes and the very low-density lipoprotein cholesterol receptors (VLDL-R) of the adipocytes, which then subsequently reduced pathogenic lipid uptake and clearance/sequestration. Moreover, it might improve cholesterol accumulation and augment toll-like receptor function in macrophages, which supported inflammatory responses. Accordingly, PCSK9 might show detrimental effects on immune host response and survival in sepsis. However, the exact roles of PCSK9 in the pathogenesis of sepsis are still not well defined. In this review, we summarized the literatures focusing on the roles of PCSK9 in sepsis. Our review provided an additional insight in the role of PCSK9 in sepsis, which might serve as a potential target for the treatment of sepsis.

Download Full-text

Preventive Strategies for Management of COVID-19 Using Natural Molecules

10.21203/rs.3.rs-24587/v1 ◽

2020 ◽

Author(s):

Yogesh Arun Dound ◽

Sameer Chaudhary ◽

Sapana Sameer Chaudhary ◽

Malik M Ahmad ◽

Mohammed H Geesi ◽

...

Keyword(s):

Viral Infections ◽

Specific Treatment ◽

World Health Organisation ◽

World Health ◽

Treatment Modalities ◽

Fatal Disease ◽

Traditional Medicines ◽

The World ◽

Life Threatening ◽

Almost All

Abstract The COVID19, a fatal disease by coronavirus (SARS-CoV-2) in late 2019 in China is now pandemic caused severe acute respiratory syndrome. The pandemic of COVID-19 has reached almost all regions of the world including territories with the death toll of more than 35,000. It has been estimated that one out every six-person affected by COVID-19 developed life-threatening conditions. The difficulty is that there are no vaccines or no specific treatment modalities for the management of COVID-19, apart from symptomatic treatments. Efforts for the development of vaccines and other specific treatment modalities are co-ordinated by the World Health Organisation (WHO), with many clinical trials ongoing with modern and traditional medicines. In this regard, various Phyto-actives from the plants are getting analyzed, which has earlier shown to be effective in various viral infections. Therefore, keeping the world scenario and due to the lack of vaccine, we have in silico studied the activity of tetrahydrocurcumin, a major metabolite of curcumin, a household spice, matairesinol, a major compound in wheat bran or flaxseed and vitamin K2-7 against both SARS-CoV's main peptide and COVID-19 Mpro.

Download Full-text