Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.

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Hemophagocytic Lymphohistiocytosis: A Life Threatening Cytopenic Condition

Faridpur Medical College Journal ◽

10.3329/fmcj.v15i2.53897 ◽

2021 ◽

Vol 15 (2) ◽

pp. 98-102

Author(s):

Suranjit Kumar Saha ◽

MM Shahin Ul Islam ◽

Nasir Uddin Ahmed ◽

Prativa Saha

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Clinical Manifestations ◽

Specific Treatment ◽

Gene Mutations ◽

Multiple Organ ◽

Treatment Modalities ◽

Hematopoietic Stem ◽

Organ Systems ◽

Life Threatening ◽

Poor Outcomes

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that occurs in many underlying conditions in all age. This is characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells and macrophages resulting in raised cytokine level. Those cytokines and immune mediated injury occur in multiple organ systems. It may be primary and secondary. Primary HLH is familial, childhood presentation and associated with gene mutations. Secondary HLH is acquired, adulthood presentation that occurs in infections, malignancies inflammatory and autoimmune diseases etc. Clinical manifestations include fever, splenomegaly, lymphadenopathy, neurologic dysfunction, coagulopathy, features of sepsis etc. Laboratory investigation includes cytopenias, hypertriglyceridemia, hyperferritinemia, abnormal liver function, hemophagocytosis, and diminished NKcell activity. Treatment modalities include immunosuppressive, immunomodulatory agents, cytostatic drugs, T-cell antibodies, anticytokine agents and hematopoietic stem cell transplantation (HSCT). Besides those, aggressive supportive care combined with specific treatment of the precipitating factor can produce better outcome. With treatment more than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management. Faridpur Med. Coll. J. 2020;15(2): 98-102

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The Contribution of Host Cells to Pneumocystis Immunity: An Update

Pathogens ◽

10.3390/pathogens8020052 ◽

2019 ◽

Vol 8 (2) ◽

pp. 52 ◽

Cited By ~ 3

Author(s):

Patricia Otieno-Odhiambo ◽

Sean Wasserman ◽

J. Claire Hoving

Keyword(s):

Treatment Strategies ◽

Pneumocystis Pneumonia ◽

Host Cells ◽

Causative Organism ◽

Aids Patients ◽

Host Immune Responses ◽

Life Threatening ◽

New Treatment ◽

Poor Outcomes ◽

Immunodeficiency Syndrome

Pneumocystis is a ubiquitous atypical fungus that is distributed globally. The genus comprises morphologically similar but genetically heterogeneous species that have co-evolved with specific mammalian hosts as obligate intra-pulmonary pathogens. In humans, Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP) in immunocompromised individuals, a serious illness frequently leading to life-threatening respiratory failure. Initially observed in acquired immunodeficiency syndrome (AIDS) patients, PCP is increasingly observed in immunocompromised non-AIDS patients. The evolving epidemiology and persistently poor outcomes of this common infection will require new strategies for diagnosis and treatment. A deeper understanding of host immune responses and of the cells that mediate them will improve the chance of developing new treatment strategies. This brief review provides an update on recent studies on the role of host immunity against Pneumocystis.

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A fatal toxic shock-like syndrome post COVID-19 infection in a child

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01070-z ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Houda Ajmi ◽

Wissem Besghaier ◽

Wafa Kallala ◽

Abdelhalim Trabelsi ◽

Saoussan Abroug

Keyword(s):

Ejection Fraction ◽

Pediatric Intensive Care ◽

Fresh Frozen Plasma ◽

Multiple Organ ◽

Clinical Feature ◽

Fresh Frozen ◽

Life Threatening ◽

High Doses ◽

Definition Of ◽

High Level

Abstract Background Children affected by Coronavirus disease 2019 (COVID-19) showed various manifestations. Some of them were severe cases presenting with multi-system inflammatory syndrome (MIS-C) causing multiple organ dysfunction. Case presentation We report the case of a 12-year-old girl with recent COVID-19 infection who presented with persistent fever, abdominal pain and other symptoms that meet the definition of MIS-C. She had lymphopenia and a high level of inflammatory markers. She was admitted to pediatric intensive care unit since she rapidly developed refractory catecholamine-resistant shock with multiple organ failure. Echocardiography showed a small pericardial effusion with a normal ejection fraction (Ejection Fraction = 60%) and no valvular or coronary lesions. The child showed no signs of improvement even after receiving intravenous immunoglobulin, fresh frozen plasma, high doses of Vasopressors and corticosteroid. His outcome was fatal. Conclusion Pediatric patients affected by the new COVID-19 related syndrome may show severe life-threatening conditions similar to Kawasaki disease shock syndrome. Hypotension in these patients results from heart failure and the decreased cardiac output. We report a new severe clinical feature of SARS-CoV-2 infection in children in whom hypotension was the result of refractory vasoplegia.

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Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

Molecules ◽

10.3390/molecules26113442 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3442

Author(s):

Yaowared Chulikhit ◽

Wichitsak Sukhano ◽

Supawadee Daodee ◽

Waraporn Putalun ◽

Rakvajee Wongpradit ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Morris Water Maze Test ◽

Object Recognition Test ◽

Pueraria Mirifica ◽

Beneficial Effects ◽

Maze Test ◽

Y Maze ◽

Tnf Α ◽

17Β Estradiol

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

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Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420974893 ◽

2020 ◽

Vol 34 ◽

pp. 205873842097489

Author(s):

Jiang Wang ◽

Bo Wang ◽

Xin Lv ◽

Yingjie Wang

Keyword(s):

Alveolar Bone ◽

Immune Cell ◽

Critical Role ◽

Therapeutic Drug ◽

Mice Model ◽

T Helper 17 ◽

Th17 Cell Differentiation ◽

Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

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Blockage of angiotensin II type 1 receptor regulates TNF-α-induced MAdCAM-1 expression via inhibition of NF-κB translocation to the nucleus and ameliorates colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00264.2009 ◽

2010 ◽

Vol 298 (2) ◽

pp. G255-G266 ◽

Cited By ~ 22

Author(s):

Takashi Mizushima ◽

Makoto Sasaki ◽

Tomoaki Ando ◽

Tsuneya Wada ◽

Mamoru Tanaka ◽

...

Keyword(s):

Angiotensin Ii ◽

Activity Index ◽

Body Weight Loss ◽

Disease Activity Index ◽

Wild Type ◽

Inflammatory Conditions ◽

Tnf Α ◽

Novel Target ◽

Colitis Model

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to α4β7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R−/−) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-α, but did not inhibit phosphorylation of p38 MAPK or of IκB that modulate MAdCAM-1 expression. However, NF-κB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R−/− than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R−/− than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-κB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

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Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0414 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Michele Mussap ◽

Vassilios Fanos

Keyword(s):

Molecular Mechanisms ◽

Vascular Dysfunction ◽

Asymptomatic Infection ◽

Multiple Organ ◽

Therapeutic Interventions ◽

Patient Specific ◽

Wide Range ◽

Life Threatening ◽

The Individual ◽

Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

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Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3135 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3135-3135

Author(s):

Yan Leyfman ◽

Nancy Emmanuel ◽

Aleksey Tentler ◽

Jared Cappelli ◽

Timothy K Erick ◽

...

Keyword(s):

Respiratory Illness ◽

Organ Damage ◽

Multiple Organ ◽

Therapeutic Interventions ◽

Actual Number ◽

Data Registry ◽

Number Of Patients ◽

Increased Risk ◽

Life Threatening ◽

Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

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URIC ACID LEVEL AS A PREDICTOR OF SEVERITY IN PREGNANT WOMEN WITH SEVERE PREECLAMPSIA

10.36106/gjra/3119272 ◽

2021 ◽

pp. 327-331

Author(s):

Natasya Natasya ◽

Fidel Ganis Siregar ◽

Ratna Akbari Ganie

Keyword(s):

Developing Countries ◽

Uric Acid ◽

Pregnant Women ◽

Acid Level ◽

Developed Countries ◽

Multiple Organ ◽

Live Births ◽

Obstetric Emergency ◽

Organ Systems ◽

Life Threatening

Preeclampsia is a pregnancy syndrome affecting multiple organ systems, characterized by hypertension and proteinuria after 20 weeks of gestation. The incidence of preeclampsia is estimated to be 3-10% of pregnancies worldwide and is the leading cause of death for pregnant women. Preeclampsia is a life-threatening obstetric emergency, so it needs prompt and precise treatment to prevent morbidity and mortality. WHO estimates that the incidence of preeclampsia is seven times higher in developing countries (2.8% of live births) than in developed countries 1,2 (0.4%).

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Severe invasive disease caused by hypervirulent Klebsiella pneumoniae: a case report

10.22514/sv.2021.052 ◽

2021 ◽

Keyword(s):

Klebsiella Pneumoniae ◽

Patient Outcomes ◽

Liver Abscess ◽

Pathogenic Bacteria ◽

Treatment Options ◽

Invasive Disease ◽

Multiple Organ ◽

Multiple Organ Dysfunction ◽

Antimicrobial Drugs ◽

Life Threatening

Klebsiella pneumoniae (K. pneumoniae) is a common pathogenic bacteria that causes numerous infectious diseases. Hypervirulent K. pneumoniae (hvKP) can lead to invasive K. pneumoniae liver abscess syndrome, which can induce life-threatening multiple organ dysfunction syndrome or septic shock. We report a case of invasive K. pneumoniae liver abscess syndrome caused by hvKP and discuss the treatment options of this syndrome. Appropriate antimicrobial drugs should be administered to improve prognosis and prevent complications, and laboratory testing is essential to guide clinical management and optimize patient outcomes.

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