Frontiers in Molecular Biosciences

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ISSN / EISSN : 2296-889X / 2296-889X
Current Publisher: Frontiers Media SA (10.3389)
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Total articles ≅ 1,568
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, Mattia Miotto, Lorenzo Di Rienzo, Madhu Nagaraj, Michele Monti, Thaddeus W. Golbek, Giorgio Gosti, , Tobias Weidner, Daniel E. Otzen, et al.
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.690655

Abstract:
We propose a computational investigation on the interaction mechanisms between SARS-CoV-2 spike protein and possible human cell receptors. In particular, we make use of our newly developed numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular isoelectronic density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, which was unfeasible with previous methods. Our results indicate that SARS-CoV-2 uses a dual strategy: in addition to the known interaction with angiotensin-converting enzyme 2, the viral spike protein can also interact with sialic-acid receptors of the cells in the upper airways.
Shuaishuai Hu, ShaoCheng Bai, Yingying Dai, Naisu Yang, Jiali Li, Xiyu Zhang, Fan Wang, Bohao Zhao, Guolian Bao, , et al.
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.692724

Abstract:
Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Herein, we found that MITF-M overexpressing melanocytes showed high cell proliferation, reduced apoptosis, and increased melanin levels. Besides, melanin-related genes, TYR, DCT, GPNMB, and PMEL, were significantly up-regulated in MITF-M overexpressing melanocytes. Furthermore, Exogenous USP13 significantly upregulated the endogenous MITF-M protein level, downregulated USP13 significantly inhibited MITF-M protein levels, without altering MITF-M mRNA expression. In addition, USP13 upregulation mitigated the MITF-M degradation and significantly increased the half-life of MITF-M. Also, USP13 stabilized the exogenous MITF protein levels. In conclusion, the MITF-M level was regulated by USP13 deubiquitinase in melanocytes, affecting melanocytes proliferation and apoptosis. This study provides the theoretical basis for coat color transformation that could be useful in the development of the new breed in fur animals.
Congcong Cao, Qian Ma, Xinbo Huang, Aolin Li, Jun Liu, Jing Ye,
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.675683

Abstract:
N6-methyladenosine (m6A) RNA modification is the most common internal mRNA modification in mammals and has been reported to play a key role in gene expression regulation. In this study, we detected a high level of m6A methylation of the PLOD2 3′-untranslated regions (3′UTR) in renal cell carcinoma (RCC). Furthermore, we found that the high expression level of PLOD2 was a prognostic indicator for patients with RCC. A dm6ACRISPR demethylation system was performed to accurately and specifically demethylate 3′UTR of PLOD2 and caused an inactivation of PLOD2 expression. Furthermore, we also performed many in vitro experiments to confirm that PLOD2 exerted tumor promoter effects by promoting tumor proliferation and migration. In conclusion, PLOD2 mRNA demethylated by dCas13b-ALKBH5 might provide a new light on the treatment for RCC.
Letian Shan, Jinying Yang, Shijie Meng, Hongfeng Ruan, Li Zhou, Fusheng Ye, Peijian Tong, Chengliang Wu
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.648823

Abstract:
Lumbar disc herniation (LDH) possesses complex pathogenesis, which has not been well elucidated yet. To date, specific or early diagnosis of LDH remains unavailable, resulting in missed opportunity for effective treatment. According to Traditional Chinese medicine (TCM) theory, LDH can be divided into two subtypes (reality syndrome and deficiency syndrome). The purpose of this study was to analyze the metabolic disorders of LDH and its TCM subtypes and screen out potential biomarkers for LDH diagnosis. Gas chromatography coupled with mass spectrometry (GC-MS) was applied to test the urine samples from 66 participants (30 healthy volunteers, 18 LDH patients with deficiency syndrome and 18 patients with reality syndrome). PCA analysis showed a distinct separation tendency between the healthy subjects and LDH patients but no obvious separation between the different syndromes (reality syndrome and deficiency syndrome) of LDH patients. As a result, 23 metabolites were identified significantly altered in the LDH patients, as compared with the healthy subjects. The altered metabolites belong to amino acid metabolism, nucleic acid metabolism, carbohydrate metabolism, and vitamin metabolism, which are related to osteoporosis and inflammation. Our results indicate metabolic disorders of LDH and thereby propose a group of metabolic biomarkers for potential application in early diagnosis of LDH in clinic, which provide a reasonable explanation for the pathogenesis of LDH.
Iskra Araujo, Amy Henriksen, Joshua Gamsby,
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.643273

Abstract:
Despite the prevalence and well-recognized adverse effects of prenatal alcohol exposure and alcohol use disorder in the causation of numerous diseases, their potential roles in the etiology of neurodegenerative diseases remain poorly characterized. This is especially true of the rare neurodegenerative diseases, for which small population sizes make it difficult to conduct broad studies of specific etiological factors. Nonetheless, alcohol has potent and long-lasting effects on neurodegenerative substrates, at both the cellular and systems levels. This review highlights the general effects of alcohol in the brain that contribute to neurodegeneration across diseases, and then focuses on specific diseases in which alcohol exposure is likely to play a major role. These specific diseases include dementias (alcohol-induced, frontotemporal, and Korsakoff syndrome), ataxias (cerebellar and frontal), and Niemann-Pick disease (primarily a Type B variant and Type C). We conclude that there is ample evidence to support a role of alcohol abuse in the etiology of these diseases, but more work is needed to identify the primary mechanisms of alcohol’s effects.
Konstantina Thomopoulou, Chara Papadaki, Alexia Monastirioti, George Koronakis, Anastasia Mala, Despoina Kalapanida, Dimitrios Mavroudis,
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.668534

Abstract:
MicroRNAs (miRNAs) are key regulators in immune surveillance and immune escape as well as modulators in the metastatic process of breast cancer cells. We evaluated the differential expression of plasma miR-10b, miR-19a, miR-20a, miR-126 and miR-155, which regulate immune response in breast cancer progression and we investigated their clinical relevance in the outcomes of breast cancer patients. Plasma samples were obtained from early (eBC; n = 140) and metastatic (mBC; n = 64) breast cancer patients before adjuvant or first-line chemotherapy, respectively. Plasma miRNA expression levels were assessed by qRT-PCR. We revealed a 4-miRNA panel consisted of miR-19a, miR-20a, miR-126, and miR-155 able to discriminate eBC from mBC patients with an AUC of 0.802 (p < 0.001). Survival analysis in eBC patients revealed that low miR-10b and miR-155 expression was associated with shorter disease free survival (disease free survival; p = 0.012 and p = 0.04, respectively) compared to high expression. Furthermore, miR-126 expression was associated with shorter overall survival (overall survival; p = 0.045). In multivariate analysis the number of infiltrated axillary lymph nodes and low miR-10b expression independently predicted for shorter DFS (HR: 2.538; p = 0.002 and HR: 1.943; p = 0.033, respectively) and axillary lymph nodes and low miR-126 for shorter OS (HR: 3.537; p = 0.001 and HR: 2.558; p = 0.018). In the subgroup of triple negative breast cancer (TNBC) patients, low miR-155 expression independently predicted for shorter DFS (HR: 5.056; p = 0.037). Accordingly in mBC, patients with low miR-10b expression had shorter progression free survival and OS compared to patients with high expression (p = 0.0017 and p = 0.042, respectively). In multivariate analysis, recurrent disease and low miR-10b expression independently predicted for shorter PFS (HR: 2.657; p = 0.001 and HR: 1.920; p = 0.017, respectively), whereas performance status two independently predicted for shorter OS (HR: 2.031; p = 0.03). In summary, deregulated expression of circulating miRNAs involved in tumor and immune cell interactions evaluated before adjuvant and 1st-line chemotherapy can distinguish disease status and emerge as independent predictors for outcomes of breast cancer patients.
, Venkat Kumar Govindarajan, , Santhi Venkatapathy
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.637378

Abstract:
The COVID-19 is affecting thousands of peoples day by day and continues to spread across the world. The present review has focused on promising repurposing drugs, including remdesivir, lopinvar/retinovar, favipiravir, hydroxychloroquine, monoclonal antibodies and vaccines against the SARS-CoV-2 infection. Besides, our review has also focused on many organizations that are in the race to develop vaccines using various approaches including DNA, RNA, viral vectors and subunit proteins against this highly contagious respiratory disease. The spike protein is being studied by scientists all over the world to develop potential vaccines. The antiviral drugs, antibodies and vaccines developed by various researchers around the world have entered clinical trials in humans. The current clinical trials for antiviral agents and vaccines with promising outcomes are being discussed. So far, four vaccines developed by the Pfizer-BioNTech vaccine, the Johnson and Johnson vaccine and two AstraZeneca vaccines (produced by SKBio in the Republic of Korea and Serum Institute of India) are approved by the World Health Organization for public use.
Jing Gao, Weili Chu, Jiali Duan, Junlu Li, Wentao Ma, Chunling Hu, Mengying Yao, , Yuejie Yang
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.640763

Abstract:
Background: Influenza virus is a common pathogen causing community-acquired pneumonia. After H1N1 infection, some patients present with rapid disease progression and various respiratory complications, especially immunocompromised patients and pregnant women. However, most patients have a favorable prognosis. Influenza viruses infect respiratory epithelial cells, leading to diffuse alveolar damage (DAD), which could induce secondary bacterial or fungal infections that could lead to serious complications, such as acute respiratory failure, severe pneumonia, pneumothorax, mediastinal emphysema, acute respiratory distress syndrome (ARDS) and post-ARDS fibrosis. Objective: The short-term mortality rate of ARDS is decreasing, and understanding survivors’ posthospitalization outcomes is very important. Our aim was to evaluate the outcomes of 69 patients who survived H1N1 pneumonia with severe respiratory complications and abnormal CT findings and developed post-ARDS pulmonary fibrosis. Materials and methods: The 280 inpatients included in this trial had been diagnosed with H1N1 infection that was confirmed by pharyngeal sputum or swab tests. The data were collected from January 2018 to January 2020 in the First Affiliated Hospital of Zhengzhou University and the Sixth People's Hospital of Zhengzhou. Of these patients, 232 had CT findings indicating pulmonary fibrosis after H1N1 infection, and 69 survived and consented to participate in this study. 6°months after diagnosis, the 69 surviving patients were interviewed and underwent physical examinations, CT scans, 6°min walk tests, and quality-of-life evaluations (SF-36). We analyzed the baseline variables and six-month outcomes of post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia. Results: Of the 69 surviving patients with post-ARDS pulmonary fibrosis, there were 24 females and 45 males, with a mean age of 53.7 ± 16.8°years; 18 patients (26%) had no underlying disease, and 14 (20%) patients had more than one underlying disease. The distance walked in 6°min increased from an average of 451.9°m at 3°months to 575.4°m at 6°months; the mean 36-Item Short Form Survey (SF-36) physical function score increased from an average of 75.3 at 3°months to 77.5 at 6°months; and the average CT score decreased from 31.3 at 3°months to 14.8 at 6°months. Treatment with systemic corticosteroids and the presence of an underlying disease were related to the CT score and the distance walked in 6°min. Conclusion: Among the survivors with pulmonary fibrosis after H1N1 influenza, the 6°min walk test and CT scores continued to be affected after 6°months. The 6°min walk distance and imaging findings improved during the first 6°months. The health-related QoL (HRQoL) scores of H1N1 pneumonia survivors were lower than those of sex- and age-matched controls.
Xiaoping Wang, Changhong Zhang, Meixuan Gong, Chen Jiang
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.687113

Abstract:
Purpose: Our purpose was to investigate the effect of lncRNA MEF2C antisense RNA 1 (MEF2C-AS1) on cervical cancer and further explore its underlying molecular mechanisms. Methods: The proliferation, migration and invasion of CC cells were determined by counting Kit-8 (CCK-8), colony formation assay, and transwell assays, respectively. qRT-PCR and western blot were conducted to quantitatively detect the expression of lncRNA MEF2C-AS1, miR-592 and R-spondin1 (RSPO1). Kaplan-Meier survival curve from the Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) website was used to describe the overall survival. Bioinformatics analysis was performed to search the downstream target of lncRNA MEF2C-AS1 and miR-592. Luciferase reporter assay was conducted to detect the interaction between lncRNA MEF2C-AS1 and miR-592 or miR-592 and RSPO1. Results: The data from GEPIA website showed that lncRNA MEF2C-AS1 expression was down-regulated in CC tissues and also associated with survival rate of CC patients. Moreover, the results of qRT-PCR also showed lncRNA MEF2C-AS1 was lowly expressed in CC cells. Subsequently, we confirmed that overexpression of lncRNA MEF2C-AS1 inhibited the proliferation, migration and invasion of CC cells. Further research illustrated that lncRNA MEF2C-AS1 was the target of miR-592, and RSPO1 was the downstream target gene of miR-592. Importantly, functional research findings indicated that lncRNA MEF2C-AS1 inhibited CC via suppressing miR-592 by targeting RSPO1. Conclusion: In our study, we demonstrated the functional role of the lncRNA MEF2C-AS1-miR-592-RSPO1 axis in the progression of CC, which provides a latent target for CC treatment.
, Sarah El-Messeiry
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.682581

Abstract:
Tissue engineering provides new hope for the combination of cells, scaffolds, and bifactors for bone osteogenesis. This is achieved by mimicking the bone’s natural behavior in recruiting the cell’s molecular machinery for our use. Many researchers have focused on developing an ideal scaffold with specific features, such as good cellular adhesion, cell proliferation, differentiation, host integration, and load bearing. Various types of coating materials (organic and non-organic) have been used to enhance bone osteogenesis. In the last few years, RNA-mediated gene therapy has captured attention as a new tool for bone regeneration. In this review, we discuss the use of RNA molecules in coating and delivery, including messenger RNA (mRNA), RNA interference (RNAi), and long non-coding RNA (lncRNA) on different types of scaffolds (such as polymers, ceramics, and metals) in osteogenesis research. In addition, the effect of using gene-editing tools—particularly CRISPR systems—to guide RNA scaffolds in bone regeneration is also discussed. Given existing knowledge about various RNAs coating/expression may help to understand the process of bone formation on the scaffolds during osseointegration.
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