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18 pages, 4228 KiB

Open AccessArticle

CCN1-Mediated Signaling in Placental Villous Tissues after SARS-CoV-2 Infection in Term Pregnant Women: Implications for Dysregulated Angiogenesis

by Yuyang Ma, Liyan Duan, Beatrix Reisch, Rainer Kimmig, Antonella Iannaccone and Alexandra Gellhaus

Curr. Issues Mol. Biol. 2024, 46(4), 3533-3550; https://doi.org/10.3390/cimb46040221 - 18 Apr 2024

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Abstract

The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism [...] Read more.

The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism of the vascular inflammation-promoting, cysteine-rich protein 61 (CYR61/CCN1) in this context. All analyses were performed in term pregnant women infected with or without SARS-CoV-2. The sFlt-1, PlGF, and sEng serum levels were quantified using ELISA. Placental protein expressions were examined by immunoblot and immunostaining. Additionally, the effect of CCN1 protein on SGHPL-5 trophoblast cells was examined. We found that SARS-CoV-2 activated the inflammatory response in pregnant women, leading to pronounced vascular alterations in placental villous tissues. Elevated serum anti-angiogenic factors (sFlt-1, sEng) upon SARS-CoV-2 infection may directly contribute to these pathological changes. Upregulated CCN1 and pNF-κB in placental villous tissues of infected patients are identified as crucial factors in placental alterations. As a conclusion, CCN1 was significantly elevated in the placentas of term pregnant women infected with SARS-CoV-2. By activating a cascade of inflammatory responses, CCN1 induced the production of the anti-angiogenic factors sFlt-1 and sEng, which may lead to abnormal placental vascular architecture. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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15 pages, 3991 KiB

Open AccessArticle

Disruption of the Functional Activity of Neutrophil Granulocytes as a Risk Factor for the Development of Lung Damage in Pregnant Women with COVID-19

by Irina Anatolyevna Andrievskaya, Egor Mikhailovich Ustinov, Karen Sargisovich Lyazgian, Nataliya Alexandrovna Ishutina and Inna Victorovna Dovzhikova

Curr. Issues Mol. Biol. 2024, 46(2), 1121-1135; https://doi.org/10.3390/cimb46020071 - 25 Jan 2024

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Abstract

Currently, the assessment of immune status in patients with COVID-19 is limited to determining the count of polymorphonuclear leukocytes and the phagocytic function of neutrophils, which is insufficient to understand the regulatory role of innate immunity cells in the development of pneumonia. However, [...] Read more.

Currently, the assessment of immune status in patients with COVID-19 is limited to determining the count of polymorphonuclear leukocytes and the phagocytic function of neutrophils, which is insufficient to understand the regulatory role of innate immunity cells in the development of pneumonia. However, no such studies have been conducted in pregnant women with COVID-19. The aim of this study was to investigate the functional state of neutrophil granulocytes in order to identify predictors of pneumonia severity risk in pregnant women with COVID-19. A clinical characterization of pregnant women with COVID-19 in addition to minimal and average lung changes was provided. The composition and ratio of morphological forms of leukocyte cells were studied. Cytochemical studies of neutrophil granulocytes were carried out and calculations of the mean cytological index (MCI) for succinate dehydrogenase, myeloperoxidase, and cationic proteins were performed. The number of NETs in blood smears was counted. Independent predictors of pneumonia severity in pregnant women with COVID-19 were calculated using regression analysis. The quality of the model was assessed using ROC analysis. In pregnant women with COVID-19 and an average volume of lung changes, the number of polymorphonuclear leukocytes (p = 0.03) and band neutrophils (p = 0.002) in the blood was significantly higher than in pregnant women with minimal lung changes. The MCI indicators of succinate dehydrogenase, cationic proteins, and myeloperoxidase in pregnant women with COVID-19 were reduced in relation to the control group (p < 0.0001). In blood smears of pregnant women with COVID-19 and an average volume of lung changes, the number of NETs increased (p = 0.002). Regression analysis showed that succinate dehydrogenase and NETs are independent predictors of pneumonia severity in pregnant women with COVID-19. Our study confirms the prognostic significance of low levels of neutrophilic succinate dehydrogenase and high levels of NETs in the blood of pregnant women with COVID-19. The combination of these two biomarkers is a significant reflection of the severity of pneumonia development in pregnant women with COVID-19. However, further research is needed to identify the mechanisms underlying this association. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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12 pages, 2905 KiB

Open AccessArticle

Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway

by Jaehoon Bae, Hyung-Jun Kwon, Ji Sun Park, Jinseok Jung, Young Bae Ryu, Woo Sik Kim, Ju Huck Lee, Jae-Ho Jeong, Jae Sung Lim, Woo Song Lee and Su-Jin Park

Curr. Issues Mol. Biol. 2023, 45(3), 2284-2295; https://doi.org/10.3390/cimb45030147 - 9 Mar 2023

Cited by 3 | Viewed by 2101

Abstract

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and [...] Read more.

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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21 pages, 11399 KiB

Open AccessArticle

Vaccine- and Breakthrough Infection-Elicited Pre-Omicron Immunity More Effectively Neutralizes Omicron BA.1, BA.2, BA.4 and BA.5 Than Pre-Omicron Infection Alone

by Eveline Santos da Silva, Jean-Yves Servais, Michel Kohnen, Victor Arendt, Georges Gilson, Therese Staub, Carole Seguin-Devaux and Danielle Perez-Bercoff

Curr. Issues Mol. Biol. 2023, 45(2), 1741-1761; https://doi.org/10.3390/cimb45020112 - 19 Feb 2023

Cited by 3 | Viewed by 1998

Abstract

Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors. Here we compared the neutralization of Omicron sublineages BA.1, BA.2, BA.4 and BA.5 by human sera collected from individuals who were infected with the ancestral B.1 [...] Read more.

Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors. Here we compared the neutralization of Omicron sublineages BA.1, BA.2, BA.4 and BA.5 by human sera collected from individuals who were infected with the ancestral B.1 (D614G) strain, who were vaccinated (3 doses) or with breakthrough infection with pre-Omicron strains (Gamma or Delta). All Omicron sublineages exhibited extensive escape from all sera when compared to the ancestral B.1 strain and to Delta, albeit to different levels depending on the origin of the sera. Convalescent sera were unable to neutralize BA.1, and partly neutralized BA.2, BA.4 and BA.5. Vaccinee sera partly neutralized BA.2, but BA.1, BA.4 and BA.5 evaded neutralizing antibodies (NAb). Some breakthrough infections (BTI) sera were non-neutralizing. Neutralizing BTI sera had similar neutralizing ability against all Omicron sublineages. Despite similar levels of anti-Spike and anti-Receptor Binding Domain (RBD) antibodies in all groups, BTI sera had the highest cross-neutralizing ability against all Omicron sublineages and convalescent sera were the least neutralizing. Antibody avidity inferred from the NT50:antibody titer ratio was highest in sera from BTI patients, underscoring qualitative differences in antibodies elicited by infection or vaccination. Together, these findings highlight the importance of vaccination to trigger highly cross-reactive antibodies that neutralize phylogenetically and antigenically distant strains, and suggest that immune imprinting by first generation vaccines may restrict, but not abolish, cross-neutralization. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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Review

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15 pages, 861 KiB

Open AccessReview

Potential New Inflammatory Markers in Bronchiectasis: A Literature Review

by Francesco Rocco Bertuccio, Nicola Baio, Simone Montini, Valentina Ferroni, Vittorio Chino, Lucrezia Pisanu, Marianna Russo, Ilaria Giana, Alessandro Cascina, Valentina Conio, Amelia Grosso, Erica Gini, Federica Albicini, Angelo Guido Corsico and Giulia Maria Stella

Curr. Issues Mol. Biol. 2024, 46(7), 6675-6689; https://doi.org/10.3390/cimb46070398 - 29 Jun 2024

Viewed by 842

Abstract

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With [...] Read more.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease’s natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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13 pages, 772 KiB

Open AccessReview

Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19

by Jiaoyue Dong, Dingyuan Su, Binbin Zhao, Jiayang Han, Mengjie Tu, Kaifeng Zhang, Fengling Wang and Yang An

Curr. Issues Mol. Biol. 2024, 46(7), 6633-6645; https://doi.org/10.3390/cimb46070395 - 28 Jun 2024

Viewed by 2554

Abstract

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway [...] Read more.

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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16 pages, 675 KiB

Open AccessReview

The Influence of Neurotrophins on the Brain–Lung Axis: Conception, Pregnancy, and Neonatal Period

by Federica D’Amico, Cecilia Lugarà, Giovanni Luppino, Carlo Giuffrida, Ylenia Giorgianni, Eleonora Maria Patanè, Sara Manti, Antonella Gambadauro, Mariarosaria La Rocca and Tiziana Abbate

Curr. Issues Mol. Biol. 2024, 46(3), 2528-2543; https://doi.org/10.3390/cimb46030160 - 15 Mar 2024

Cited by 2 | Viewed by 1384

Abstract

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific [...] Read more.

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD). Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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19 pages, 378 KiB

Open AccessReview

Antioxidant Intake and Biomarkers of Asthma in Relation to Smoking Status—A Review

by Naser A. Alsharairi

Curr. Issues Mol. Biol. 2023, 45(6), 5099-5117; https://doi.org/10.3390/cimb45060324 - 10 Jun 2023

Cited by 4 | Viewed by 2236

Abstract

Asthma is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of asthma, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in [...] Read more.

Asthma is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of asthma, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in several OS and inflammatory biomarkers. However, studies suggest significant differences in OS and inflammation biomarkers between smokers and nonsmokers. A few studies suggest associations between antioxidant intake from diet/supplements and asthma in patients with different smoking status. Evidence is lacking on the protective role of antioxidant vitamin and/or mineral consumption against asthma by smoking status with respect to inflammation and OS biomarkers. Therefore, the aim of this review is to highlight current knowledge regarding the relations between antioxidant intake, asthma, and its associated biomarkers, according to smoking status. This paper can be used to guide future research directions towards the health consequences of antioxidant intake in smoking and nonsmoking asthmatics. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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