scholarly journals Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

2020 ◽  
Vol 21 (19) ◽  
pp. 7189
Author(s):  
Eileen M McGowan ◽  
Nahal Haddadi ◽  
Najah T. Nassif ◽  
Yiguang Lin
Keyword(s):  
Viral Replication ◽  
Acute Disseminated Encephalomyelitis ◽  
Vascular Protection ◽  
Comprehensive Overview ◽  
Beneficial Effects ◽  
The World ◽  
Sphingosine 1 Phosphate ◽  
Life Threatening ◽  
Psychiatric Complications ◽  
Tract Infections

The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

Bitter Melon: A Multifunctional Medicinal Plant with Powerful Bioactive Compounds

2021 ◽  
Author(s):  
Fadime Eryılmaz Pehlivan
Keyword(s):  
Bioactive Compounds ◽  
Biological Activities ◽  
Folk Medicine ◽  
Bitter Melon ◽  
Comprehensive Overview ◽  
Tropical Regions ◽  
Beneficial Effects ◽  
Life Saving ◽  
The World ◽  
Treatment Of Diabetes

Nature is full of poisons as well as life-saving entities. Extracts of natural products in medicinal plants have been used for thousands of years in traditional medicine throughout the World. Bitter melon (Momordica charantia) is a member of Cucurbitaceae family, widely distributed in tropical regions of the World, that has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. It contains phytochemicals, flavonoids, triterpenes, saponins, ascorbic acid, steroids, proteins, and polysaccharides. This plant is a traditional herbal medicine, possesses various biological, medicinal activities and pharmacological functions, namely antidiabetic, anthelmintic, contraceptive, antimalarial, laxative, antihyperglycemic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, and anti-inflammatory activities of M. charantia have been reported. Its fruit has a special bitter taste, parts of M. charantia, such as fruits, vines, leaves and even roots have been used as folk medicine for the remedy of diseases like toothache, diarrhea, and diabetes. It is also used for the treatment of eczema, gout, jaundice, pneumonia, psoriasis, and rheumatism. These beneficial effects are attributed to the various bioactive components of M. charantia, which are important sources of phytoconstituents used to treat various diseases since ancient times. This chapter reviews various aspects of the results of investigations involving M. charantia in the recent years, providing a comprehensive overview of the phytochemical application of M. charantia to attract more attention to their biological activities for better utilization of M. charantia; focusing on the review of benefits that bitter melon offers in terms of its potential as a source of bioactive compounds and its role in the control of different diseases.

scholarly journals Pseudomonas aeruginosa Secreted Biomolecules and Their Diverse Functions in Biofilm Formation and Virulence

2021 ◽  
Author(s):  
Theerthankar Das
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Extracellular Dna ◽  
World Health ◽  
Negative Bacterium ◽  
Major Infection ◽  
The World ◽  
Life Threatening ◽  
Health Organization ◽  
Tract Infections ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium accountable for causing life-threatening infections in humans. According to the World Health Organization, P. aeruginosa classified as a critical pathogen. Specifically, P. aeruginosa in its colonized or biofilm state presents a major infection threat to immunocompromised (HIV) patients, Cystic fibrosis, burns, wounds and surgery associated infection. It is also a common pathogen responsible for causing hospital acquired/nosocomial infection and Urinary tract infections. P. aeruginosa biofilm is made up of bacterial self-synthesized biomolecules includes extracellular DNA, polysaccharides, proteins, RNA, siderophores and metabolites such as pyocyanin. This chapter will elaborate the manifold functions of P. aeruginosa secreted biomolecules in establishing and stabilizing biofilms, triggering virulence and pathogenicity in host, and resisting antibiotics and antibacterial agents.

scholarly journals Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 151
Author(s):  
Alexie Mayor ◽  
Adélaïde Chesnay ◽  
Guillaume Desoubeaux ◽  
David Ternant ◽  
Nathalie Heuzé-Vourc’h ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Inflammatory Diseases ◽  
Treatment Strategies ◽  
Candida Spp ◽  
Medical Needs ◽  
Life Threatening ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Unmet Medical Needs

Respiratorytract infections (RTIs) are frequent and life-threatening diseases, accounting for several millions of deaths worldwide. RTIs implicate microorganisms, including viruses (influenza virus, coronavirus, respiratory syncytial virus (RSV)), bacteria (Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus and Bacillus anthracis) and fungi (Pneumocystis spp., Aspergillus spp. and very occasionally Candida spp.). The emergence of new pathogens, like the coronavirus SARS-CoV-2, and the substantial increase in drug resistance have highlighted the critical necessity to develop novel anti-infective molecules. In this context, antibodies (Abs) are becoming increasingly important in respiratory medicine and may fulfill the unmet medical needs of RTIs. However, development of Abs for treating infectious diseases is less advanced than for cancer and inflammatory diseases. Currently, only three Abs have been marketed for RTIs, namely, against pulmonary anthrax and RSV infection, while several clinical and preclinical studies are in progress. This article gives an overview of the advances in the use of Abs for the treatment of RTIs, based on the analysis of clinical studies in this field. It describes the Ab structure, function and pharmacokinetics, and discusses the opportunities offered by the various Ab formats, Ab engineering and co-treatment strategies. Including the most recent literature, it finally highlights the strengths, weaknesses and likely future trends of a novel anti-RTI Ab armamentarium.

Comparativa de modelos multivariados basados en aprendizaje automático para la predicción del riesgo de diabetes en etapas tempranas

2021 ◽  
Author(s):  
◽  
Zayra Ramírez Gaytán
Keyword(s):  
World Health ◽  
Degenerative Diseases ◽  
Decision Tree Algorithm ◽  
Data Set ◽  
The World ◽  
Long Time ◽  
Life Threatening ◽  
Health Organization ◽  
Logistic Regression Algorithm ◽  
Asymptomatic Phase

Diabetes is one of the fastest-growing, life-threatening, chronic degenerative diseases. According to the World Health Organization (WHO), it has affected 422 million people worldwide in 2018. Approximately 50% of all people who suffer diabetes are not diagnosed due to the asymptomatic phase which usually lasts a long time. In this work, a data set of 520 instances has been used. The data set has been analyzed with the next three algorithms: logistic regression algorithm, decision trees and random forest. The results show that the decision tree algorithm had better performance with an AUC of 98%. Also, it was found the most common symptoms that a person with a risk of diabetes presents are polyuria, polydipsia and sudden weight loss.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies

2021 ◽  
pp. 1-39
Author(s):  
Kevin Morris ◽  
Mohammad Nami ◽  
Joe F. Bolanos ◽  
Maria A. Lobo ◽  
Melody Sadri-Naini ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Neurological Disorders ◽  
World Economy ◽  
Disease Burden ◽  
The United States ◽  
Fast Tracking ◽  
The World ◽  
Life Threatening ◽  
The Cost ◽  
The Impact

Neurological disorders significantly impact the world’s economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population’s economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Cancer: A Life Threatening Peril Becoming Lifestyle Disease

2021 ◽  
pp. 03
Author(s):  
Sara Hayee ◽  
Amna Rehman
Keyword(s):  
Cancer Patients ◽  
Urban Areas ◽  
Past History ◽  
The World ◽  
Cause Of Deaths ◽  
Life Threatening ◽  
Abnormal Cells ◽  
Lifestyle Disease ◽  
First Time ◽  
Day By Day

Caner a dreadful disease is actually one large group of diseases which dates back to times of “Hippocrates”, The Father of Medicine, (460-370BC) who used this name for the first time to talk about non-ulcer and ulcer forming tumors. Theevidence of its presence from the very past history comes from fossilized “Egyptian Mummies” having tumors on bones. Then Galen (130-200 AD) used the term “Oncos” to explain tumors. So it's a disease involving growth of abnormal cells, their proliferation and metastasizing the other tissues and organs. Now we know that biology has a branch namedOncology to deal with the scientific study of cancer and oncogenes. It took centuries to get knowledge and use modern technologies against this malady. Now we know cancer is a group disease which has hundreds of types. 19th Century saw much advancement towards its cure. Along with surgery, radiotherapy and chemotherapy were the main methods to cure cancer patients. Day by day, scientists are looking for new methods to control and cure of this curse. Hundreds of natural medicinal compounds are being tested to use clinically for its cure in order to replace the radiotherapy andchemotherapy and lower their side effects. But humanity is still fighting against this disease as the numbers of cases throughout the world are increasing day by day. If we look on the reports p r e s e n t e d b y W H O ( W o r l d H e a l t hOrganization), Cancer is the second leading cause of deaths globally which means one person in every six deaths, dies due to cancer. In 2018, the most common types of cancers reported in men were of liver, prostate, stomach, lung andcolorectal. Whereas in females the most common forms were breast, thyroid, cervical and colorectal. Cancer has become a global disasterfamily of the patient. It imparts physical, emotional and financial crisis. Unfortunately, the condition is bitterer in under developing countries. Cancer has become a lifestyle disease these days. We are living in the world withsuperficial comfort but we are breathing with urbanizations, ozone depletion, exposure to microwave and ultraviolet radiations, hazardous chemicals etc. Moreover, It is becoming a lifestyle disease due to lack of exercise, Obesity, consumptions of drugs, tobacco and alcohols. The cases of cancers are reported more in urban areas than in rural areasmore likely due to above mentioned factors. The ratio of cancer patients is expected to raise up-to 27.5 million by 2040 globally. So the battle is never ending, Humans need to figure out the factors and cutting these from their lives in orderto live a healthy life which is a blessing indeed. which is not only crunching the cancer patient but it also has damaging effects on the whole

Abstract 1746: Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Mediates Vascular Repair By HDL Receptor Activation And Sphingosine Kinase (SK-1)/Sphingosine 1-Phosphate (S1P) Dependent Nitric Oxide (NO) Generation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sergio Li Calzi ◽  
Jennifer L Kielczewski ◽  
Evan McFarland ◽  
Kyung Hee Chang ◽  
Aqeela Afzal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Scavenger Receptor ◽  
Receptor Activation ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Sphingosine 1 Phosphate ◽  
Active Motor ◽  
Umbilical Vein Endothelial Cells ◽  
Igfbp 3

Purpose: We demonstrated that IGFBP-3 stimulates hematopoietic stem cells (HSC) to differentiate into endothelial cells, form capillaries, and stabilize the vasculature (Chang, et al, PNAS 2007). Local IGFBP- 3 production is increased by hypoxia and facilitates the homing of HSC to areas of injury. In the circulation, IGFBP-3 is bound to HDL. In this study, we investigated the signaling pathways responsible for the robust migratory effects of IGFBP-3. Methods: The effects of IGFBP-3 on NO generation in human vascular precursors (CD 34 + , CD14 − ), human lung microvascular endothelial cells, and human umbilical vein endothelial cells were examined using DAF-FM fluorescence. Western analysis was use for detection of eNOS and vasodilator-stimulated phosphoprotein (VASP), which redistributes to lamellipodia forming an active motor complex that supports motility and is phosphorylated in response to NO. Localization of VASP was performed by immunohistochemistry. SK-1 was assessed following IGFBP-3 stimulation. Results: In CD34 + cells and endothelial cells, IGFBP-3 stimulated eNOS phosphorylation at Ser1177 (102 ± 1.8%, P = 0.0002) and increased NO generation (275 ± 50%, P = 0.05) by increasing SK-1 and S1P generation. IGFBP-3 was bound and internalized by the HDL receptor, scavenger receptor 1B (SR1B). NO generation following IGFBP-3 exposure was reduced by SK inhibitors or SR-1B blocking antibody pretreatment (35 ± 5%, P < 0.02). IGFBP-3 generated NO increased phosphorylation of VASP at Ser239 and promoted the redistribution of VASP to lamellipodia. Conclusions: IGFBP-3 effects on cell migration are NO dependent and mediated in part by activation of the HDL receptor SR1B suggesting that some of the beneficial effects of HDL are mediated by the association of IGFBP-3.

scholarly journals Blockchain technology in maritime industry

Pomorstvo ◽  
2020 ◽  
Vol 34 (1) ◽  
pp. 178-184
Author(s):  
Ivan Peronja ◽  
Kristijan Lenac ◽  
Roko Glavinović
Keyword(s):  
Comparative Method ◽  
Maritime Industry ◽  
Comprehensive Overview ◽  
Time Value ◽  
Bill Of Lading ◽  
Blockchain Technology ◽  
The World ◽  
Transportation Process ◽  
Potential Impact ◽  
World Environment

Maritime industry is one of the most globally connected industries that include transportation of numerous types of goods and documents across the world. With that said, it is safe to say that abundance of financial and paper-trail transactions are made every day in order for goods to be transported from one place to another. The scope of this paper is to show that by implementing blockchain technology savings in time and money could be generated. This paper presents costs of container freights and rates in the last few years and assumes possible future costs of container freights and rates if blockchain based technology is implemented. Additionally, by using comparative method economical and time value of “traditional” bill of lading is compared with a blockchain bill of lading solution. It is also important to mention the potential impact of the blockchain technology on the world environment and ecology by reducing global paper consumption and emissions from vehicles that are used in the transportation process. This paper also gives a descriptive and comprehensive overview of current and future applications of blockchain technology in maritime industry.

The Barretstown Experience: A Rite of Passage

2009 ◽  
Vol 17 (2) ◽  
pp. 72-89 ◽  
Author(s):  
Peter J. Kearney
Keyword(s):  
Therapeutic Recreation ◽  
Rite Of Passage ◽  
Beneficial Effects ◽  
Childhood Illnesses ◽  
Life Threatening ◽  
Effects On Children ◽  
Ritual Process ◽  
Holiday Camp ◽  
Transitional Phase

Barretstown Castle Holiday Camp for seriously ill children may have long-term beneficial effects on children with life-threatening illnesses. The presented evidence suggests that the experience is a contemporary rite of passage. The different stages of separation, transition and reaggregation can be identified. The separation from family and civil society is remarkably complete. Established norms no longer prevail in the transitional phase of liminality. Communitas and I-thou relationships become the mode of interaction. Barretstown added the dimension of Therapeutic Recreation to an American camp experience. The structured sequences of Therapeutic Recreation mediated by caras (councillors) encourage personal change. The Barretstown experience may be a life-enhancing ritual process and an important social experience in chronic severe childhood illnesses.

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