scholarly journals Systemic effects of the hormonal treatment of male hypogonadism with preliminary indications for the management of COVID-19 patients

2020 ◽  
Vol 11 ◽  
pp. 204201882096643
Author(s):  
Rossella Cannarella ◽  
Aldo E. Calogero ◽  
Rosita A. Condorelli ◽  
Antonio Aversa ◽  
Sandro La Vignera
Keyword(s):  
Molecular Mechanisms ◽  
Negative Impact ◽  
Hormonal Treatment ◽  
Epidemiological Studies ◽  
Host Cells ◽  
Systemic Effects ◽  
Male Hypogonadism ◽  
Novel Coronavirus ◽  
Low Serum

Male hypogonadism, defined as an inadequate production of testosterone (T), is associated with a greater morbidity and mortality. Epidemiological studies identified T deficiency as a risk factor for cardiovascular disease. Also, low serum T levels impact on glucose homeostasis through a worse glucose uptake, utilization, and disposal, and the general negative impact on metabolism. The aim of this review is to provide a comprehensive and updated overview of the effects of T replacement therapy on metabolic and cardiovascular systems and prostate tissue in patients with hypogonadism, including molecular mechanisms through which T exerts its actions. Furthermore, recent findings on novel coronavirus disease (COVID-19) epidemiology have shown a greater mortality in male compared with female patients and a role of T in promoting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection of the host cells has been demonstrated. Hence, the secondary aim of this review is to provide preliminary indications on the management in patients with COVID-19.

Mannose-binding lectin genetics: from A to Z

2008 ◽  
Vol 36 (6) ◽  
pp. 1461-1466 ◽  
Author(s):  
Peter Garred
Keyword(s):  
Epidemiological Studies ◽  
Mannose Binding Lectin ◽  
Host Cells ◽  
Lectin Pathway ◽  
Mannose Binding ◽  
The Stability ◽  
Genetically Determined ◽  
Micro Organisms ◽  
Binding Lectin

MBL (mannose-binding lectin) is primarily a liver-derived collagen-like serum protein. It binds sugar structures on micro-organisms and on dying host cells and is one of the four known mediators that initiate activation of the complement system via the lectin pathway. Common variant alleles situated both in promoter and structural regions of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variations in MBL serum concentrations influence the susceptibility to and the course of different types of infectious, autoimmune, neoplastic, metabolic and cardiovascular diseases, but this is still a subject under discussion. The fact that these genetic variations are very frequent, indicates a dual role of MBL. This overview summarizes the current molecular understanding of human MBL2 genetics.

Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases

2019 ◽  
Vol 25 (12) ◽  
pp. 1345-1371 ◽  
Author(s):  
Tanzir Rafe ◽  
Parvez Ahmed Shawon ◽  
Liyad Salem ◽  
Nafij Imtiyaj Chowdhury ◽  
Farjana Kabir ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Long Run

Background:Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer’s, hypertension, stroke, cysts and cancers.Methods:This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information.Results:Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases.Conclusion:This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

The Significance of Age-Related Androgen Depletion in Cognitive Impairment: A Review

2004 ◽  
Vol 5 (2) ◽  
pp. 166-176
Author(s):  
Melanie S. Burkhardt ◽  
Jonathan K. Foster ◽  
Ralph N. Martins
Keyword(s):  
Cognitive Decline ◽  
Hormonal Treatment ◽  
Hormone Treatment ◽  
Epidemiological Studies ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Androgen Depletion ◽  
Potential Interactions ◽  
Considerable Support

AbstractThe potential role of supplementing sex steroids for the prevention and delay of age-related cognitive decline has received a great deal of recent interest. Although the biological plausibility of hormone treatment has received considerable support, clinical studies of cognitive functioning after hormonal treatment in postmenopausal women with and without dementia have produced mixed results. Much less attention has been given to the corresponding role of androgens in men. In order to establish the relevance of hormonal supplementation for men in delaying or preventing cognitive decline, it is of importance to evaluate both adrenal and gonadal contributions to androgen status. Additionally, consideration must also be given to the potential interactions of androgens with risk and protective factors (e.g., apolipoprotein E genotype and education). Here we review experimental and epidemiological studies of the significance of androgens for cognitive function.

scholarly journals Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1818
Author(s):  
Victor Norris ◽  
Judit Ovádi
Keyword(s):  
Drug Targets ◽  
Controlled Trial ◽  
Host Cells ◽  
Immunomodulatory Agents ◽  
Randomized Controlled ◽  
Treatment And Prevention ◽  
Scientific World ◽  
One Year ◽  
Novel Coronavirus

A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments.

scholarly journals Insulin resistance and cancer: the role of insulin and IGFs

2012 ◽  
Vol 20 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Sefirin Djiogue ◽  
Armel Hervé Nwabo Kamdje ◽  
Lorella Vecchio ◽  
Maulilio John Kipanyula ◽  
Mohammed Farahna ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Proliferation ◽  
Energy Metabolism ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Epidemiological Studies ◽  
High Energy

Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

scholarly journals Insertional Inactivation of Prevotella intermedia OxyR Results in Reduced Survival with Oxidative Stress and in the Presence of Host Cells

2021 ◽  
Vol 9 (3) ◽  
pp. 551
Author(s):  
Mariko Naito ◽  
B. Ross Belvin ◽  
Mikio Shoji ◽  
Qin Gui ◽  
Janina P. Lewis
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Anaerobic Bacteria ◽  
Host Cells ◽  
Pcr Analysis ◽  
Prevotella Intermedia ◽  
Allelic Exchange ◽  
Important Target ◽  
Insertional Inactivation

One of the most abundant bacteria in the subgingival pockets of patients with bleeding following mechanical periodontal therapy is Prevotella intermedia. However, despite its abundance, the molecular mechanisms of its contribution to periodontal disease are not well known. This is mainly due to the lack of genetic tools that would allow examination of the role of predicted virulence factors in the pathogenesis of this bacterium. Here, we report on the first mutant in the P. intermedia OMA14 strain. The mutation is an allelic exchange replacement of the sequences coding for a putative OxyR regulator with ermF sequences coding for the macrolide–lincosamide resistance in anaerobic bacteria. The mutant is severely impaired in its ability to grow with eukaryotic cells, indicating that it is an important target for interventional strategies. Further analyses reveal that its ability to grow with oxidative stress species, in the form of hydrogen peroxide and oxygen, is severely affected. Transcriptome analysis reveals that the major deregulated genes code for the alkylhydroperoxide reductase system, AhpCF, mediating protection from peroxide stress. Moreover, genes coding for Dps, CydA and Ftn are downregulated in the mutant strain, as further verified using qRT-PCR analysis. In conclusion, we succeeded in generating the first P. intermedia mutant and show that the OxyR-deficient strain is unable to survive with a variety of host cells as well as with oxidative stress.

scholarly journals Androgens in SARS-CoV-2 Coronavirus Infections

2021 ◽  
pp. S145-S151
Author(s):  
L STÁRKA ◽  
M DUŠKOVÁ
Keyword(s):  
Androgen Deprivation ◽  
Host Cells ◽  
General Effect ◽  
Androgenic Alopecia ◽  
Cancer Treatments ◽  
Clinical Observations ◽  
Novel Coronavirus ◽  
Prostate Cancer Treatments ◽  
Androgen Levels

Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

COVID 19: Camostat and The Role of Serine Protease Entry Inhibitor TMPRSS2

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Host Cell ◽  
Serine Protease ◽  
Cellular Protein ◽  
Host Cells ◽  
The Novel ◽  
Robert Koch Institute ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

According to the latest research, the novel coronavirus uses the protein angiotensin-converting enzyme 2 (ACE-2) as a receptor for docking to the host cell. Essential for entry is the priming of the spike (S) protein of the virus by host cell proteases. A broadly based team led by infection biologists from the German Primate Centre and with the participation of the Charité Hospital in Berlin, the Hanover Veterinary University Foundation, the BG-UnfallklinikMurnau, the LMU Munich, the Robert Koch Institute and the German Centre for Infection Research wanted to find out how SARS-CoV-2 enters host cells and how this process can be blocked [1]. They have published their findings in the journal "Cell" [1]. The team of scientists was initially able to confirm that SARS-CoV-2 docks to the host cell via the ACE-2 receptor. They also identified Transmembrane serine protease 2 (TMPRSS2) as the cellular protein responsible for entry into the cell [1-3].

scholarly journals Order and disorder: abnormal 3D chromatin organization in human disease

2020 ◽  
Vol 19 (2) ◽  
pp. 128-138 ◽  
Author(s):  
Chiara Anania ◽  
Darío G Lupiáñez
Keyword(s):  
Molecular Mechanisms ◽  
Biological Function ◽  
Three Dimensional ◽  
Systemic Effects ◽  
Form Complex ◽  
Order And Disorder ◽  
Wide Range ◽  
Causes Of Disease ◽  
Fundamental Forces

Abstract A precise three-dimensional (3D) organization of chromatin is central to achieve the intricate transcriptional patterns that are required to form complex organisms. Growing evidence supports an important role of 3D chromatin architecture in development and delineates its alterations as prominent causes of disease. In this review, we discuss emerging concepts on the fundamental forces shaping genomes in space and on how their disruption can lead to pathogenic phenotypes. We describe the molecular mechanisms underlying a wide range of diseases, from the systemic effects of coding mutations on 3D architectural factors, to the more tissue-specific phenotypes resulting from genetic and epigenetic modifications at specific loci. Understanding the connection between the 3D organization of the genome and its underlying biological function will allow a better interpretation of human pathogenesis.

scholarly journals The Phospholipid Profile of Mycoplasmas

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jonathan D. Kornspan ◽  
Shlomo Rottem
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Inflammatory Responses ◽  
Polar Lipids ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Ether Lipids ◽  
Mycoplasma Cell ◽  
Phospholipid Profile

Thede novosynthesized polar lipids ofMycoplasmaspecies are rather simple, comprising primarily of the acidic glycerophospholipids PG and CL. In addition, when grown in a medium containing serum, significant amounts of PC and SPM are incorporated into the mycoplasma cell membrane although these lipids are very uncommon in wall-covered bacteria. The exogenous lipids are either incorporated unchanged or the PC incorporated is modified by a deacylation-acylation enzymatic cycle to form disaturated PC. Although their small genome, in someMycoplasmaspecies, other genes involved in lipid biosynthesis were detected, resulting in the synthesis of a variety of glycolipis, phosphoglycolipids and ether lipids. We suggest that analyses and comparisons of mycoplasma polar lipids may serve as a novel and useful tool for classification. Nonetheless, to evaluate the importance of polar lipids in mycoplasma, further systematic and extensive studies on moreMycoplasmaspecies are needed. While studies are needed to elucidate the role of lipids in the mechanisms governing the interaction of mycoplasmas with host eukaryotic cells, the finding that a terminal phosphocholine containing glycolipids ofM. fermentansserves both as a major immune determinants and as a trigger of the inflammatory responses, and the findings that the fusogenicity ofM. fermentanswith host cells is markedly stimulated by lyso-ether lipids, are important steps toward understanding the molecular mechanisms ofM. fermentanspathogenicity.

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