The role of PCSK9 in infectious diseases.

2021 ◽  
Vol 28 ◽  
Author(s):  
Laura Magnasco ◽  
Chiara Sepulcri ◽  
Roberta Maria Antonello ◽  
Stefano Di Bella ◽  
Laura Labate ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Malaria Infection ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Physiological Role ◽  
Protective Role ◽  
Loss Of Function ◽  
Pcsk9 Inhibition ◽  
Sepsis And Septic Shock

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. Objective: This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases. Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.

scholarly journals Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Jesús Chávez-Reyes ◽  
Carlos E. Escárcega-González ◽  
Erika Chavira-Suárez ◽  
Angel León-Buitimea ◽  
Priscila Vázquez-León ◽  
...  
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Influenza A ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Clinical Findings ◽  
Uncontrolled Diabetes ◽  
Patients With Diabetes ◽  
The Impact

Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

Treatment of ebola and other infectious diseases: melatonin “goes viral”

2020 ◽  
Vol 3 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Russel J Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma
Keyword(s):  
Mortality Rate ◽  
Infectious Diseases ◽  
Hemorrhagic Shock ◽  
Safety Profile ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Attractive Potential ◽  
Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.  

Role of cannabinoids in various diseases: A review

2021 ◽  
Vol 23 ◽  
Author(s):  
Simran Kaur ◽  
Nikita Sharma ◽  
Arpita Roy
Keyword(s):  
Infectious Diseases ◽  
Metabolic Disorders ◽  
Viral Infections ◽  
Cannabis Sativa ◽  
Endocannabinoid System ◽  
Psychological Disorders ◽  
Bioactive Compound ◽  
The Body ◽  
Therapeutic Aspect

Background: The plant, Cannabis sativa is heavily explored and researched with many industrial and pharmaceutical applications. The medicinal and therapeutic role of cannabis Sativa has been summarized in the paper, citing its mechanism of action and influence on the human body. Diseases like metabolic disorders, infectious diseases, and psychological disorders pose negative and long-term drastic effects on the body like neurodegeneration and other chronic system failures. Several existing literature has proved its effectiveness against such diseases. Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders. Method: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to form a well-informed and information-heavy manuscript. Here we tried to summaries the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids in various diseases. Result: This review highlights the various constituents which are present in Cannabis sativa, the Endocannabinoid system, and the role of cannabinoids in various diseases Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.

IMPACT OF INFECTIOUS DISEASES ON PUBERTAL TIMING IN UKRAINIAN GIRLS: RESULTS A MULTICENTER STUDY

2021 ◽  
Vol 74 (10) ◽  
pp. 2392-2399
Author(s):  
Aidyn G. Salmanov ◽  
Orusia A. Kovalyshyn ◽  
Roman S. Scoreiko ◽  
Victor M. Zinchenko ◽  
Serhiy M. Baksheev ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Age Of Onset ◽  
Final Height ◽  
Pubertal Development ◽  
Age At Onset ◽  
Peak Height ◽  
Height Velocity ◽  
Peak Height Velocity

The aim: To determine current age at the initiation of puberty for Ukrainian school-aged girls and infections impact to puberty. Materias and methods: We performed a multicentre cohort study. The analyses are based on data that were collected and evaluated biannually on Ukrainian school girls aged 6-17 years from 5 regions of Ukraine. Pubertal development was classified according to the Marshall and Tanner criteria. Results: Overall, 2,784 girls have been included in the study. Mean age of onset of puberty in Ukrainian girls was 10.1±1.0 yrs. Age of onset of pubic hair was 11.0±1.0 yrs and that of axillary hair was 11.6±1.0 yrs. Mean age in girls of menarche was 12.2±0.9 yrs. There were no significant correlations between age at onset of puberty and body mass index, final height, total peak height velocity, duration of puberty, and peak height velocity. A total of 2,420 infectious diseases were diagnosted. Of these, 64.8% were viral and 35.2% bacterial infections, respectively. Ukrainian girls with infectious diseases (especially viral infections) had older age at pubertal onset and positive association of infections in childhood with late age of menarche. Conclusions: Infectious morbidity (especially viral infections) in girls may be associated with later puberty. The lowering of the number of infections in childhood could be an additional factor that contributes to earlier puberty. To reduce infectious diseases, more attention should be paid to the vaccination of children.

scholarly journals Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

2020 ◽  
Vol 22 (1) ◽  
pp. 42
Author(s):  
Lorenzo Belluomini ◽  
Alberto Caldart ◽  
Alice Avancini ◽  
Alessandra Dodi ◽  
Ilaria Trestini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Infectious Diseases ◽  
Cancer Patients ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Current Evidence ◽  
Human Immune Deficiency Virus ◽  
Prognostic Impact ◽  
Lung Cancer Patients

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.

scholarly journals Cow Milk Lactoferrin Possesses Several Catalytic Activities

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 208 ◽  
Author(s):  
Svetlana E. Soboleva ◽  
Sergey E. Sedykh ◽  
Ludmila I. Alinovskaya ◽  
Valentina N. Buneva ◽  
Georgy A. Nevinsky
Keyword(s):  
Transcriptional Activation ◽  
Growth Regulation ◽  
Rna Binding ◽  
Viral Infections ◽  
3D Structure ◽  
Three Dimensional ◽  
Physiological Role ◽  
Protective Role ◽  
Cow Milk ◽  
Dna And Rna

Lactoferrin (LF) is a Fe3+-binding glycoprotein, that was first recognized in milk and then in other epithelial secretions and barrier body fluids to which many different functions have been attributed to LF including protection from iron-induced lipid peroxidation, immunomodulation, cell growth regulation, DNA and RNA binding, as well as transcriptional activation, etc. The polyfunctional physiological role of LF is still unclear, but it has been suggested to be responsible for primary defense against microbial and viral infections. It was shown previously that human milk LF possesses several enzymatic activities: DNase, RNase, ATPase, phosphatase, and amylase. Analysis of human, cow, horse, buffalo and camel LF showed a highly conserved three-dimensional (3D) structure including only detail differences in the species. Recently, it was shown that similar to human cow LF possesses DNase and RNase activities. Using different methods here we have shown for the first time that LFs from the milk of seven cows of different breeds possess high peroxidase, protease, amylase, protease, and phosphatase activities. Protease activity of cow LFs was activated by Mg2+ and Ca2+ ions. In contrast to human LFs, ATPase activity was revealed only in three of seven cow LF preparations. The discovery that LF possesses these activities may contribute to understanding the multiple physiological functions of this extremely polyfunctional protein including its protective role against microbial and viral infections.

Treatment: infectious diseases

2018 ◽  
Author(s):  
David A. Warrell ◽  
Matthew Dryden ◽  
Alastair Miller ◽  
Clare Morgan ◽  
David A. Warrell
Keyword(s):  
Infectious Diseases ◽  
Sexually Transmitted Infections ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Emerging Infections ◽  
Sexually Transmitted

Introduction: infectious diseases - Viral infections - Bacterial infections - Malaria - Other protozoal infections - Filarial worms - Worm infections - Flukes - Emerging infections - Sexually transmitted infections

scholarly journals Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy

2019 ◽  
Vol 20 (14) ◽  
pp. 3596 ◽  
Author(s):  
Yuki Tochigi ◽  
Yutaka Takamatsu ◽  
Jun Nakane ◽  
Rika Nakai ◽  
Kentaro Katayama ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Rat Model ◽  
Physiological Role ◽  
Early Death ◽  
Neurite Growth ◽  
Loss Of Function ◽  
Age Related ◽  
Putative Tumor Suppressor ◽  
Severe Reduction

WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (lde/lde). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. lde/lde cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.

scholarly journals Caenorhabditits elegans LRK-1 and PINK-1 Act Antagonistically in Stress Response and Neurite Outgrowth

2009 ◽  
Vol 284 (24) ◽  
pp. 16482-16491 ◽  
Author(s):  
Julia Sämann ◽  
Jan Hegermann ◽  
Erika von Gromoff ◽  
Stefan Eimer ◽  
Ralf Baumeister ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Parkinson Disease ◽  
Neurite Outgrowth ◽  
Physiological Role ◽  
Model Organisms ◽  
Loss Of Function ◽  
C Elegans ◽  
Genes Encoding

Mutations in two genes encoding the putative kinases LRRK2 and PINK1 have been associated with inherited variants of Parkinson disease. The physiological role of both proteins is not known at present, but studies in model organisms have linked their mutants to distinct aspects of mitochondrial dysfunction, increased vulnerability to oxidative and endoplasmic reticulum stress, and intracellular protein sorting. Here, we show that a mutation in the Caenorhabditits elegans homologue of the PTEN-induced kinase pink-1 gene resulted in reduced mitochondrial cristae length and increased paraquat sensitivity of the nematode. Moreover, the mutants also displayed defects in axonal outgrowth of a pair of canal-associated neurons. We demonstrate that in the absence of lrk-1, the C. elegans homologue of human LRRK2, all phenotypic aspects of pink-1 loss-of-function mutants were suppressed. Conversely, the hypersensitivity of lrk-1 mutant animals to the endoplasmic reticulum stressor tunicamycin was reduced in a pink-1 mutant background. These results provide the first evidence of an antagonistic role of PINK-1 and LRK-1. Due to the similarity of the C. elegans proteins to human LRRK2 and PINK1, we suggest a common role of both factors in cellular functions including stress response and regulation of neurite outgrowth. This study might help to link pink-1/PINK1 and lrk-1/LRRK2 function to the pathological processes resulting from Parkinson disease-related mutants in both genes, the first manifestations of which are cytoskeletal defects in affected neurons.

scholarly journals Circadian Clock and OxInflammation: Functional Crosstalk in Cutaneous Homeostasis

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Frigato ◽  
Mascia Benedusi ◽  
Anna Guiotto ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi
Keyword(s):  
Circadian Clock ◽  
Redox Homeostasis ◽  
Physiological Role ◽  
Protective Role ◽  
Circadian System ◽  
Circadian Disruption ◽  
Cellular Damage ◽  
Lifestyle Risk Factors

Circadian rhythms are biological oscillations that occur with an approximately 24 h period and optimize cellular homeostasis and responses to environmental stimuli. A growing collection of data suggests that chronic circadian disruption caused by novel lifestyle risk factors such as shift work, travel across time zones, or irregular sleep-wake cycles has long-term consequences for human health. Among the multiplicity of physiological systems hypothesized to have a role in the onset of pathologies in case of circadian disruption, there are redox-sensitive defensive pathways and inflammatory machinery. Due to its location and barrier physiological role, the skin is a prototypical tissue to study the influence of environmental insults induced OxInflammation disturbance and circadian system alteration. To better investigate the link among outdoor stressors, OxInflammation, and circadian system, we tested the differential responses of keratinocytes clock synchronized or desynchronized, in an in vitro inflammatory model exposed to O3. Being both NRF2 and NF-κB two key redox-sensitive transcription factors involved in cellular redox homeostasis and inflammation, we analyzed their activation and expression in challenged keratinocytes by O3. Our results suggest that a synchronized circadian clock not only facilitates the protective role of NRF2 in terms of a faster and more efficient defensive response against environmental insults but also moderates the cellular damage resulting from a condition of chronic inflammation. Our results bring new insights on the role of circadian clock in regulating the redox-inflammatory crosstalk influenced by O3 and possibly can be extrapolated to other pollutants able to affect the oxinflammatory cellular processes.

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