scholarly journals Hemoglobin E, malaria and natural selection

2019 ◽  
Vol 2019 (1) ◽  
pp. 232-241
Author(s):  
Jiwoo Ha ◽  
Ryan Martinson ◽  
Sage K Iwamoto ◽  
Akihiro Nishi
Keyword(s):  
Natural Selection ◽  
Malaria Infection ◽  
Meta Analysis ◽  
Evolutionary Genetics ◽  
Protective Role ◽  
Epidemiologic Studies ◽  
Hemoglobin E ◽  
Selection For

Abstract It is known that there has been positive natural selection for hemoglobin S and C in humans despite negative health effects, due to its role in malaria resistance. However, it is not well understood, if there has been natural selection for hemoglobin E (HbE), which is a common variant in Southeast Asia. Therefore, we reviewed previous studies and discussed the potential role of natural selection in the prevalence of HbE. Our review shows that in vitro studies, evolutionary genetics studies and epidemiologic studies largely support an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria infection. However, the evidence is inconsistent, provided from different regions, and insufficient to perform an aggregated analysis such as a meta-analysis. In addition, few candidate gene, genome-wide association or epistasis studies, which have been made possible with the use of big data in the post-genomic era, have investigated HbE. The biological pathways linking HbE and malaria infection have not yet been fully elucidated. Therefore, further research is necessary before it can be concluded that there was positive natural selection for HbE due to protection against malaria. Lay summary: Our review shows that evidence largely supports an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria. However, the evidence is not consistent. Further research is necessary before it is concluded.

scholarly journals Fibroblast Growth Factor 20 Gene Polymorphism in Parkinson’s Disease in Asian Population: A Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 674
Author(s):  
Han-Lin Chiang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Meta Analysis ◽  
Lewy Bodies ◽  
Asian Population ◽  
Protective Role ◽  
Lewy Neurites ◽  
Chinese Populations ◽  
Study Results

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3′ untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = −3.96; p < 0.0001) and the dominant models (Z = −4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.

scholarly journals Dose dependence of efficacy but not of safety in sublingual immunotherapy

2016 ◽  
Vol 65 (1) ◽  
Author(s):  
F. Frati ◽  
C. Incorvaia ◽  
F. Marcucci ◽  
L. Sensi ◽  
G. Di Cara ◽  
...  
Keyword(s):  
Sublingual Immunotherapy ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Dose Dependence ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Systemic Reactions ◽  
Significant Difference

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

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.

Protective role of epithelium in the guinea pig airway

1989 ◽  
Vol 66 (4) ◽  
pp. 1547-1552 ◽  
Author(s):  
M. Munakata ◽  
I. Huang ◽  
W. Mitzner ◽  
H. Menkes
Keyword(s):  
Guinea Pig ◽  
Protective Role ◽  
Airway Epithelial ◽  
Serosal Side ◽  
Epithelial Surface ◽  
Airway Responses ◽  
Airway Tone ◽  
Stimulation Of

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466–471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

scholarly journals Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?

2018 ◽  
Vol 11 (4) ◽  
pp. 121 ◽  
Author(s):  
Matteo Tacelli ◽  
Ciro Celsa ◽  
Bianca Magro ◽  
Aurora Giannetti ◽  
Grazia Pennisi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Meta Analysis ◽  
Pancreatic Beta Cell ◽  
Protective Role ◽  
Antidiabetic Drugs ◽  
Alcoholic Fatty Liver ◽  
Compensated Cirrhosis ◽  
Ppar Γ ◽  
Insulin Use

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

2003 ◽  
Vol 1 (3) ◽  
pp. 113-117 ◽  
Author(s):  
M. Myronidou ◽  
B. Kokkas ◽  
A. Kouyoumtzis ◽  
N. Gregoriadis ◽  
A. Lourbopoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Normal Function ◽  
No Production ◽  
Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

scholarly journals Protocatechuic acids protects against high glucose- induced insulin resistance in human visceral adipose tissue

2016 ◽  
Vol 62 (5) ◽  
pp. 45-46
Author(s):  
Paulina Ormazabal ◽  
Beatrice Scazzocchio ◽  
Rosaria Varì ◽  
Annunziata Iacovelli ◽  
Roberta Masella
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Glucose ◽  
Protective Role ◽  
Insulin Sensitizer ◽  
20 Nm ◽  
Visceral Adipose

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

scholarly journals Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

2020 ◽  
Vol 8 (7) ◽  
pp. 1087
Author(s):  
Manuela Donalisio ◽  
Simona Cirrincione ◽  
Massimo Rittà ◽  
Cristina Lamberti ◽  
Andrea Civra ◽  
...  
Keyword(s):  
Breast Milk ◽  
Extracellular Vesicles ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Protective Role ◽  
Surface Proteins ◽  
Human Colostrum ◽  
Clinical Illness

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

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