Life | April 2021 - Browse Articles

11 pages, 667 KiB

Open AccessArticle

Human Prostate Epithelial Cells Activate the AIM2 Inflammasome upon Cellular Senescence: Role of POP3 Protein in Aging-Related Prostatic Inflammation

by Ravichandran Panchanathan, Vaikundamoorthy Ramalingam, Hongzhu Liu and Divaker Choubey

Life 2021, 11(4), 366; https://doi.org/10.3390/life11040366 - 20 Apr 2021

Cited by 13 | Viewed by 2588

Abstract

Increased levels of type I (T1) interferon (IFN)-inducible POP3 protein in myeloid cells inhibit activation of the AIM2 inflammasome and production of IL-1β and IL-18 proinflammatory cytokines. The AIM2 mRNA levels were significantly higher in benign prostate hyperplasia (BPH) than the normal prostate. [...] Read more.

Increased levels of type I (T1) interferon (IFN)-inducible POP3 protein in myeloid cells inhibit activation of the AIM2 inflammasome and production of IL-1β and IL-18 proinflammatory cytokines. The AIM2 mRNA levels were significantly higher in benign prostate hyperplasia (BPH) than the normal prostate. Further, human normal prostate epithelial cells (PrECs), upon becoming senescent, activated an inflammasome. Because in aging related BPH senescent PrECs accumulate, we investigated the role of POP3 and AIM2 proteins in pre-senescent and senescent PrECs. Here we report that the basal levels of the POP3 mRNA and protein were lower in senescent (versus young or old) PrECs that exhibited activation of the T1 IFN response. Further, treatment of PrECs and a BPH cell line (BPH-1) that expresses the androgen receptor (AR) with the male sex hormone dihydrotestosterone (DHT) increased the basal levels of POP3 mRNA and protein, but not AIM2, and inhibited activation of the AIM2 inflammasome. Of interest, a stable knockdown of POP3 protein expression in the BPH-1 cell line increased cytosolic DNA-induced activation of AIM2 inflammasome. These observations suggest a potential role of POP3 protein in aging-related prostatic inflammation. Full article

(This article belongs to the Special Issue Cellular Senescence in Health, Disease and Aging: Blessing or Curse?)

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14 pages, 3488 KiB

Open AccessArticle

Inhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cells

by Carina Colturato-Kido, Rayssa M. Lopes, Hyllana C. D. Medeiros, Claudia A. Costa, Laura F. L. Prado-Souza, Letícia S. Ferraz and Tiago Rodrigues

Life 2021, 11(4), 365; https://doi.org/10.3390/life11040365 - 20 Apr 2021

Cited by 10 | Viewed by 2997

Abstract

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells that affects children and adults. Despite the high cure rates, drug resistance still remains a significant clinical problem, which stimulates the development of new therapeutic strategies and drugs to improve [...] Read more.

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells that affects children and adults. Despite the high cure rates, drug resistance still remains a significant clinical problem, which stimulates the development of new therapeutic strategies and drugs to improve the disease outcome. Antipsychotic phenothiazines have emerged as potential candidates to be repositioned as antitumor drugs. It was previously shown that the anti-histaminic phenothiazine derivative promethazine induced autophagy-associated cell death in chronic myeloid leukemia cells, although autophagy can act as a “double-edged sword” contributing to cell survival or cell death. Here we evaluated the role of autophagy in thioridazine (TR)-induced cell death in the human ALL model. TR induced apoptosis in ALL Jurkat cells and it was not cytotoxic to normal peripheral mononuclear blood cells. TR promoted the activation of caspase-8 and -3, which was associated with increased NOXA/MCL-1 ratio and autophagy triggering. AMPK/PI3K/AKT/mTOR and MAPK/ERK pathways are involved in TR-induced cell death. The inhibition of the autophagic process enhanced the cytotoxicity of TR in Jurkat cells, highlighting autophagy as a targetable process for drug development purposes in ALL. Full article

(This article belongs to the Special Issue Biological Activities of Natural Products, Antipsychotics, and Their Derivatives)

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21 pages, 742 KiB

Open AccessReview

Multi-Omics Approaches and Radiation on Lipid Metabolism in Toothed Whales

by Jayan D. M. Senevirathna and Shuichi Asakawa

Life 2021, 11(4), 364; https://doi.org/10.3390/life11040364 - 20 Apr 2021

Cited by 2 | Viewed by 4055

Abstract

Lipid synthesis pathways of toothed whales have evolved since their movement from the terrestrial to marine environment. The synthesis and function of these endogenous lipids and affecting factors are still little understood. In this review, we focused on different omics approaches and techniques [...] Read more.

Lipid synthesis pathways of toothed whales have evolved since their movement from the terrestrial to marine environment. The synthesis and function of these endogenous lipids and affecting factors are still little understood. In this review, we focused on different omics approaches and techniques to investigate lipid metabolism and radiation impacts on lipids in toothed whales. The selected literature was screened, and capacities, possibilities, and future approaches for identifying unusual lipid synthesis pathways by omics were evaluated. Omics approaches were categorized into the four major disciplines: lipidomics, transcriptomics, genomics, and proteomics. Genomics and transcriptomics can together identify genes related to unique lipid synthesis. As lipids interact with proteins in the animal body, lipidomics, and proteomics can correlate by creating lipid-binding proteome maps to elucidate metabolism pathways. In lipidomics studies, recent mass spectroscopic methods can address lipid profiles; however, the determination of structures of lipids are challenging. As an environmental stress, the acoustic radiation has a significant effect on the alteration of lipid profiles. Radiation studies in different omics approaches revealed the necessity of multi-omics applications. This review concluded that a combination of many of the omics areas may elucidate the metabolism of lipids and possible hazards on lipids in toothed whales by radiation. Full article

(This article belongs to the Special Issue Radioactive Pollution and Biological Effects of Radioactivity)

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14 pages, 15323 KiB

Open AccessArticle

Volatile Constituents of Endophytic Fungi Isolated from Aquilaria sinensis with Descriptions of Two New Species of Nemania

by Saowaluck Tibpromma, Lu Zhang, Samantha C. Karunarathna, Tian-Ye Du, Chayanard Phukhamsakda, Munikishore Rachakunta, Nakarin Suwannarach, Jianchu Xu, Peter E. Mortimer and Yue-Hu Wang

Life 2021, 11(4), 363; https://doi.org/10.3390/life11040363 - 19 Apr 2021

Cited by 23 | Viewed by 6526

Abstract

Algae, bacteria, and fungi, as well as higher plants, produce a wide variety of secondary metabolites known as natural products. Natural products are well known as remarkable sources of many therapeutic agents. The genus Nemania is a wood-decaying fungus that belongs to family [...] Read more.

Algae, bacteria, and fungi, as well as higher plants, produce a wide variety of secondary metabolites known as natural products. Natural products are well known as remarkable sources of many therapeutic agents. The genus Nemania is a wood-decaying fungus that belongs to family Xylariaceae. Nemania is often found as an endophyte in diverse hosts and some species are known to produce useful secondary metabolites. In this study, two Nemania species were isolated as an endophytic fungus from Aquilaria sinensis. Multi-gene phylogenetic studies showed that the newly described strains of Nemania are new to science, and this is the first report of Nemania from the host Aquilaria. One of the fermented species, Nemania aquilariae (KUMCC 20-0268), resulted in five sesquiterpenoids, which were previously reported from agarwood, and their structures were identified by gas chromatography-mass spectrometry (GC-MS). In addition, five different media were investigated in vitro to optimize conditions for growing the fungal biomass of Nemania aquilariae and N. yunnanensis. Full article

(This article belongs to the Special Issue Biodiversity and Ecology of Fungi in Terrestrial and Marine Ecosystems)

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28 pages, 2338 KiB

Open AccessSystematic Review

Evaluation of Blood Levels of C-Reactive Protein Marker in Obstructive Sleep Apnea: A Systematic Review, Meta‐Analysis and Meta-Regression

by Mohammad Moslem Imani, Masoud Sadeghi, Farid Farokhzadeh, Habibolah Khazaie, Serge Brand, Kenneth M. Dürsteler, Annette Brühl and Dena Sadeghi-Bahmani

Life 2021, 11(4), 362; https://doi.org/10.3390/life11040362 - 19 Apr 2021

Cited by 29 | Viewed by 4670

Abstract

(1) Introduction: High sensitivity C-reactive protein (hs-CRP) and CRP are inflammatory biomarkers associated with several inflammatory diseases. In both pediatric and adult individuals with Obstructive Sleep Apnea (OSA) higher hs-CRP and CRP were observed, compared to controls. With the present systematic review, meta-analysis [...] Read more.

(1) Introduction: High sensitivity C-reactive protein (hs-CRP) and CRP are inflammatory biomarkers associated with several inflammatory diseases. In both pediatric and adult individuals with Obstructive Sleep Apnea (OSA) higher hs-CRP and CRP were observed, compared to controls. With the present systematic review, meta-analysis and meta-regression we expand upon previous meta-analyses in four ways: (1) We included 109 studies (96 in adults and 13 in children); (2) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of hs-CRP; (3) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of CRP; (4) we reported serum and plasma levels of both hs-CRP and CRP in children with OSA, always compared to controls. (2) Materials and Methods: The PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases were searched to retrieve articles published until 31 May 2020, with no restrictions. The data included basic information involving the first author, publication year, country of study, ethnicity of participants in each study, age, BMI, and AHI of both groups, and mean and standard deviation (SD) of plasma and serum levels of CRP and hs-CRP. (3) Results: A total of 1046 records were retrieved from the databases, and 109 studies were selected for the analysis (96 studies reporting the blood levels of hs-CRP/CRP in adults and 13 studies in children). For adults, 11 studies reported plasma hs-CRP, 44 serum hs-CRP, 9 plasma CRP, and 32 serum CRP levels. For children, 6 studies reported plasma hs-CRP, 4 serum hs-CRP, 1 plasma CRP, and 2 serum CRP levels. Compared to controls, the pooled MD of plasma hs-CRP levels in adults with OSA was 0.11 mg/dL (p < 0.00001). Compared to controls, the pooled MD of serum hs-CRP levels in adults with OSA was 0.09 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma CRP levels in adults with OSA was 0.06 mg/dL (p = 0.72). Compared to controls, the pooled MD of serum CRP levels in adults with OSA was 0.36 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma hs-CRP, serum hs-CRP, plasma hs-CRP, and serum hs-CRP in children with OSA was 1.17 mg/dL (p = 0.005), 0.18 mg/dL (p = 0.05), 0.08 mg/dL (p = 0.10), and 0.04 mg/dL (p = 0.33), respectively. The meta-regression showed that with a greater apnea-hypapnea index (AHI), serum hs-CRP levels were significantly higher. (4) Conclusions: The results of the present systematic review, meta-analysis and meta-regression showed that compared to healthy controls plasma and serum levels of hs-CRP and serum CRP level were higher in adults with OSA; for children, and compared to controls, just plasma hs-CRP levels in children with OSA were higher. Full article

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17 pages, 708 KiB

Open AccessReview

Next-Generation Sequencing Technologies and Neurogenetic Diseases

by Hui Sun, Xiao-Rong Shen, Zi-Bing Fang, Zong-Zhi Jiang, Xiao-Jing Wei, Zi-Yi Wang and Xue-Fan Yu

Life 2021, 11(4), 361; https://doi.org/10.3390/life11040361 - 19 Apr 2021

Cited by 13 | Viewed by 7072

Abstract

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct [...] Read more.

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot–Marie–Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches. Full article

(This article belongs to the Special Issue The Increasing Role of Next Generation Sequencing Methods in Mutation Analysis)

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11 pages, 275 KiB

Open AccessReview

The Use of Upconversion Nanoparticles in Prostate Cancer Photodynamic Therapy

by Michał Osuchowski, Filip Osuchowski, Wojciech Latos and Aleksandra Kawczyk-Krupka

Life 2021, 11(4), 360; https://doi.org/10.3390/life11040360 - 19 Apr 2021

Cited by 18 | Viewed by 3277

Abstract

Photodynamic Therapy (PDT) is a cancer treatment that uses light, a photosensitizer, and oxygen to destroy tumors. This article is a review of approaches to the treatment of prostate cancer applying upconversion nanoparticles (UCNPs). UCNPs have become a phenomenon that are rapidly gaining [...] Read more.

Photodynamic Therapy (PDT) is a cancer treatment that uses light, a photosensitizer, and oxygen to destroy tumors. This article is a review of approaches to the treatment of prostate cancer applying upconversion nanoparticles (UCNPs). UCNPs have become a phenomenon that are rapidly gaining recognition in medicine. They have proven to be highly selective and specific and present a powerful tool in the diagnosis and treatment of prostate cancer. Prostate cancer is a huge health problem in Western countries. Its early detection can significantly improve patients’ prognosis, but currently used diagnostic methods leave much to be desired. Recently developed methodologies regarding UCNP research between the years 2021 and 2014 for prostate cancer PDT will also be discussed. Current limitations in PDT include tissue irradiation with visible wavelengths that have a short tissue penetration depth. PDT with the objectives to synthesize UCNPs composed of a lanthanide core with a coating of adsorbed dye that will generate fluorescence after excitation with near-infrared light to illuminate deep tissue is a subject of intense research in prostate cancer. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Medicine)

15 pages, 2030 KiB

Open AccessArticle

A Comparative Analysis of Erythropoietin and Carbamoylated Erythropoietin Proteome Profiles

by Neeraj K. Tiwari, Monica Sathyanesan, Vikas Kumar and Samuel S. Newton

Life 2021, 11(4), 359; https://doi.org/10.3390/life11040359 - 19 Apr 2021

Cited by 8 | Viewed by 3524

Abstract

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity [...] Read more.

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered modification of EPO, is non-erythropoietic but retains the neurotrophic and neurotrophic activity of EPO. Blood profile analysis after EPO and CEPO administration showed that CEPO has no effect on red blood cell or platelet counts. We conducted an unbiased, quantitative, mass spectrometry-based proteomics study to comparatively investigate EPO and CEPO-induced protein profiles in neuronal phenotype PC12 cells. Bioinformatics enrichment analysis of the protein expression profiles revealed the upregulation of protein functions related to memory formation such as synaptic plasticity, long term potentiation (LTP), neurotransmitter transport, synaptic vesicle priming, and dendritic spine development. The regulated proteins, with roles in LTP and synaptic plasticity, include calcium/calmodulin-dependent protein kinase type 1 (Camk1), Synaptosomal-Associated Protein, 25 kDa (SNAP-25), Sectretogranin-1 (Chgb), Cortactin (Cttn), Elongation initiation factor 3a (Eif3a) and 60S acidic ribosomal protein P2 (Rplp2). We examined the expression of a subset of regulated proteins, Cortactin, Grb2 and Pleiotrophin, by immunofluorescence analysis in the rat brain. Grb2 was increased in the dentate gyrus by EPO and CEPO. Cortactin was induced by CEPO in the molecular layer, and pleiotrophin was increased in the vasculature by EPO. The results of our study shed light on potential mechanisms whereby EPO and CEPO produce cognitive-enhancing effects in clinical and preclinical studies. Full article

(This article belongs to the Special Issue Innovations in the Neurobiology of Neuropsychiatric Disorders)

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10 pages, 1748 KiB

Open AccessArticle

Initial Transarterial Chemoembolization (TACE) Using HepaSpheres 20–40 µm and Subsequent Lipiodol TACE in Patients with Hepatocellular Carcinoma > 5 cm

by Su Min Cho, Hee Ho Chu, Jong Woo Kim, Jin Hyung Kim and Dong Il Gwon

Life 2021, 11(4), 358; https://doi.org/10.3390/life11040358 - 18 Apr 2021

Cited by 2 | Viewed by 3712

Abstract

Purpose: To investigate clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) using HepaSpheres 20–40 µm in diameter and subsequent cisplatin-based lipiodol TACE (Cis-TACE) in patients with hepatocellular carcinoma (HCC) > 5 cm. Materials and Methods: This study included 39 consecutive patients (34 men, [...] Read more.

Purpose: To investigate clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) using HepaSpheres 20–40 µm in diameter and subsequent cisplatin-based lipiodol TACE (Cis-TACE) in patients with hepatocellular carcinoma (HCC) > 5 cm. Materials and Methods: This study included 39 consecutive patients (34 men, 5 women; mean age, 63.5 years; range, 39–80 years) who underwent DEB-TACE using HepaSpheres 20–40 µm as first-line treatment for HCC > 5 cm (mean diameter, 8.2 cm; range, 5.1–13 cm) between September 2018 and August 2019. Patients with new tumors, residual tumors, or tumor growth after initial DEB-TACE underwent subsequent Cis-TACE. Results: All 39 patients underwent initial DEB-TACE successfully, with 35 (89.7%) and three (7.7%) patients experiencing minor and major complications, respectively. After initial DEB-TACE, one patient (2.6%) achieved complete response (CR), 35 (89.7%) achieved partial response (PR), and three (7.7%) experienced progressive disease (PD). During a median follow-up period of 14.4 months (range, 0.6–23 months), 23 patients underwent Cis-TACE, with 11, three, and nine achieving CR, PR, and PD, respectively. The median overall survival time was 20.9 months (95% confidence interval (CI), 18.6–23.2 months), the median time to progression was 8.8 months (95% CI, 6.5–11.1 months), and the median time to local tumor recurrence was 16 months (95% CI, 7.4–24.6 months). Conclusions: DEB-TACE using HepaSpheres 20–40 µm in diameter can be a safe and effective initial treatment method in patients with HCC > 5 cm. Subsequent Cis-TACE constitutes a good adjuvant method to enhance tumor response after initial DEB-TACE. Full article

(This article belongs to the Special Issue Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma)

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12 pages, 477 KiB

Open AccessArticle

Determinants of Processing Speed Trajectories among Middle Aged or Older Adults, and Their Association with Chronic Illnesses: The English Longitudinal Study of Aging

by Viktor Gkotzamanis, Giorgos Koliopanos, Albert Sanchez-Niubo, Beatriz Olaya, Francisco Félix Caballero, José Luis Ayuso-Mateos, Somnath Chatterji, Josep Maria Haro and Demosthenes Panagiotakos

Life 2021, 11(4), 357; https://doi.org/10.3390/life11040357 - 18 Apr 2021

Cited by 2 | Viewed by 2417

Abstract

The aim of this study was to identify latent groups of similar trajectories in processing speed through aging, as well as factors that are associated with these trajectories. In the context of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project, [...] Read more.

The aim of this study was to identify latent groups of similar trajectories in processing speed through aging, as well as factors that are associated with these trajectories. In the context of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project, data from the English Longitudinal Study of Aging (ELSA) (n = 12099) were analyzed. Latent groups of similar trajectories in the processing scores as well as their predictors and covariates were investigated, using group-based trajectory models (GBTM). The coefficient estimates for potential group predictors correspond to parameters of multinomial logit functions that are integrated in the model. Potential predictors included sex, level of education, marital status, level of household wealth, level of physical activity, and history of smoking, while time-varying covariates included incidence of cardiovascular disease (CVD), diabetes mellitus, depressive symptoms, and sleep disturbances. Four trajectories were identified and named after their baseline scores and shapes: High (4.4%), Middle/Stable (31.5%), Low/Stable (44.5%), and Low Decline (19.6%). Female sex, higher levels of education, mild level of physical activity, having been married, and higher level of wealth were associated with a higher probability of belonging to any of the higher groups compared to the Low/Decline that was set as reference, while presence of CVD, diabetes mellitus, and depressive symptoms were associated with lower processing speed scores within most trajectories. All the aforementioned factors might be valid targets for interventions to reduce the burden of age-related cognitive impairment. Full article

(This article belongs to the Section Physiology and Pathology)

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17 pages, 7083 KiB

Open AccessArticle

Natural Product Gene Clusters in the Filamentous Nostocales Cyanobacterium HT-58-2

by Xiaohe Jin, Eric S. Miller and Jonathan S. Lindsey

Life 2021, 11(4), 356; https://doi.org/10.3390/life11040356 - 18 Apr 2021

Cited by 5 | Viewed by 3209

Abstract

Cyanobacteria are known as rich repositories of natural products. One cyanobacterial-microbial consortium (isolate HT-58-2) is known to produce two fundamentally new classes of natural products: the tetrapyrrole pigments tolyporphins A–R, and the diterpenoid compounds tolypodiol, 6-deoxytolypodiol, and 11-hydroxytolypodiol. The genome (7.85 Mbp) of [...] Read more.

Cyanobacteria are known as rich repositories of natural products. One cyanobacterial-microbial consortium (isolate HT-58-2) is known to produce two fundamentally new classes of natural products: the tetrapyrrole pigments tolyporphins A–R, and the diterpenoid compounds tolypodiol, 6-deoxytolypodiol, and 11-hydroxytolypodiol. The genome (7.85 Mbp) of the Nostocales cyanobacterium HT-58-2 was annotated previously for tetrapyrrole biosynthesis genes, which led to the identification of a putative biosynthetic gene cluster (BGC) for tolyporphins. Here, bioinformatics tools have been employed to annotate the genome more broadly in an effort to identify pathways for the biosynthesis of tolypodiols as well as other natural products. A putative BGC (15 genes) for tolypodiols has been identified. Four BGCs have been identified for the biosynthesis of other natural products. Two BGCs related to nitrogen fixation may be relevant, given the association of nitrogen stress with production of tolyporphins. The results point to the rich biosynthetic capacity of the HT-58-2 cyanobacterium beyond the production of tolyporphins and tolypodiols. Full article

(This article belongs to the Special Issue Cyanobacteria: Advances in (Meta-)Genomics and Proteomics)

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12 pages, 1915 KiB

Open AccessArticle

Long-Term Results of the Modular Physiological Wrist Prosthesis (MPW^®) in Patients with Inflammatory Diseases

by Christoph Biehl, Martin Stoll, Martin Heinrich, Lotta Biehl, Jochen Jung, Christian Heiss and Gabor Szalay

Life 2021, 11(4), 355; https://doi.org/10.3390/life11040355 - 18 Apr 2021

Cited by 2 | Viewed by 2385

Abstract

The wrist is among the predilection sites of over 90% of cases of rheumatoid arthritis (RA). In advanced cases, total wrist arthroplasty (TWA) is an alternative to arthrodesis. The aim of this study is to present the long-term results of the modular physiological [...] Read more.

The wrist is among the predilection sites of over 90% of cases of rheumatoid arthritis (RA). In advanced cases, total wrist arthroplasty (TWA) is an alternative to arthrodesis. The aim of this study is to present the long-term results of the modular physiological wrist prosthesis (MPW^®) and to match them in context with the results of a standard population survey. In a retrospective study with follow-up, patients with an MPW^® endoprosthesis were evaluated concerning the clinical and radiological outcome, complications were reviewed (incidence and type), and conversion to wrist fusion was assessed. Patient function measurements included the Mayo wrist score, the patient-specific wrist test, and therefore the DASH score (arm, shoulder, and hand). Thirty-four MPW^® wrist prostheses were implanted in 32 patients, including thirty primary implantations and four changes of the type of the endoprosthesis. Sixteen patients (18 prostheses) underwent clinical and radiological follow-up. The average follow-up time was 8.5 years (1 to 16). Poor results of the MPW prosthesis are caused by the issues of balancing with luxation and increased PE wear. Salvage procedures included revision of the TWA or fusion. In successful cases, the flexion and extension movement averaged 40 degrees. The grip force was around 2.5 kg. The common DASH score was 79 points, with limited and problematic joints of the upper extremity. The MPW wrist prosthesis offered good pain relief and functional movement in over 80% of cases. The issues of dislocation and increased PE wear prevent better long-term results, as do the joints affected. A follow-up study with fittings under a contemporary anti-rheumatic therapy with biologicals suggests increasing score results. Type of study/level of evidence: Case series, IV. Full article

(This article belongs to the Special Issue Metabolic Bone Diseases: From Classroom to Clinic)

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7 pages, 5284 KiB

Open AccessEditor’s ChoiceReview

The Three Pillars of COVID-19 Convalescent Plasma Therapy

by Massimo Franchini, Giancarlo Maria Liumbruno, Giorgio Piacentini, Claudia Glingani and Marco Zaffanello

Life 2021, 11(4), 354; https://doi.org/10.3390/life11040354 - 18 Apr 2021

Cited by 18 | Viewed by 3362

Abstract

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, [...] Read more.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, up until now, no specific and efficient pharmacological therapy has been validated. Translating the experience from previous viral epidemics, passive immunotherapy by means of plasma from individuals recovered from COVID-19 has been intensively investigated since the beginning of the pandemic. In this narrative review, we critically analyze the three factors, named “pillars”, that play a key role in determining the clinical effectiveness of this biologic therapy: the convalescent plasma, the disease (COVID-19), and the patients. Full article

(This article belongs to the Special Issue Neutralizing-Antibody-Based Treatments for COVID-19: Achievements and Lessons Learnt for Future Pandemics)

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12 pages, 691 KiB

Open AccessArticle

The Impact of Epigallocatechin Gallate and Coconut Oil Treatment on Cortisol Activity and Depression in Multiple Sclerosis Patients

by Jose Luis Platero, María Cuerda-Ballester, David Sancho-Cantus, María Benlloch, Jose Joaquin Ceron, Camila Peres Rubio, María Pilar García-Pardo, María Mar López-Rodríguez and Jose Enrique de la Rubia Ortí

Life 2021, 11(4), 353; https://doi.org/10.3390/life11040353 - 17 Apr 2021

Cited by 14 | Viewed by 4624

Abstract

(1) Background: Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), [...] Read more.

(1) Background: Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), whose main source is coconut oil, have shown emotional benefits and body fat loss. The aim of this study was to assess the impact of EGCG and coconut oil on cortisol activity related to fat loss and depression in MS patients. (2) Methods: The study involved 51 MS patients who were randomly divided into an intervention group or a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, which were included in their daily diet for four months. The control group received placebo and all patients followed an isocaloric diet. A blood sample was collected before and after the four-month period, and levels of cortisol, albumin and BHB were measured in serum. In addition, immediately before and after the intervention, anthropometric variables were measured: waist-to-hip ratio (WHR), body fat mass percentage, fat weight, total weight, and muscle mass percentage. Depression was assessed with the Beck Depression Inventory II (BDI-II). (3) Results: No significant changes were obtained in cortisol levels in any of the groups, and there was a significant increase in albumin in the blood of the intervention group only that could lead to a decrease in serum free cortisol. In addition, it was observed a significant decrease in levels of depression and abdominal fat. (4) Conclusions: EGCG combined with coconut oil increase the concentration of albumin in blood and produce less depression in MS patients. Full article

(This article belongs to the Special Issue Depressive Disorders-New Challenges)

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15 pages, 2046 KiB

Open AccessArticle

The Impact of Lifetime Alcohol and Cigarette Smoking Loads on Amyotrophic Lateral Sclerosis Progression: A Cross-Sectional Study

by Aliona Cucovici, Andrea Fontana, Andrei Ivashynka, Sergio Russo, Valentina Renna, Letizia Mazzini, Ileana Gagliardi, Jessica Mandrioli, Ilaria Martinelli, Vitalie Lisnic, Dafin Fior Muresanu, Michele Zarrelli, Massimiliano Copetti and Maurizio A. Leone

Life 2021, 11(4), 352; https://doi.org/10.3390/life11040352 - 17 Apr 2021

Cited by 7 | Viewed by 4395

Abstract

Background—Amyotrophic lateral sclerosis (ALS) is a devastating and untreatable motor neuron disease; smoking and alcohol drinking may impact its progression rate. Objective—To ascertain the influence of smoking and alcohol consumption on ALS progression rates. Methods—Cross-sectional multicenter study, including 241 consecutive patients (145 males); [...] Read more.

Background—Amyotrophic lateral sclerosis (ALS) is a devastating and untreatable motor neuron disease; smoking and alcohol drinking may impact its progression rate. Objective—To ascertain the influence of smoking and alcohol consumption on ALS progression rates. Methods—Cross-sectional multicenter study, including 241 consecutive patients (145 males); mean age at onset was 59.9 ± 11.8 years. Cigarette smoking and alcohol consumption data were collected at recruitment through a validated questionnaire. Patients were categorized into three groups according to ΔFS (derived from the ALS Functional Rating Scale-Revised and disease duration from onset): slow (n = 81), intermediate (80), and fast progressors (80). Results—Current smokers accounted for 44 (18.3%) of the participants, former smokers accounted for 10 (4.1%), and non-smokers accounted for 187 (77.6%). The age of ALS onset was lower in current smokers than non-smokers, and the ΔFS was slightly, although not significantly, higher for smokers of >14 cigarettes/day. Current alcohol drinkers accounted for 147 (61.0%) of the participants, former drinkers accounted for 5 (2.1%), and non-drinkers accounted for 89 (36.9%). The log(ΔFS) was weakly correlated only with the duration of alcohol consumption (p = 0.028), but not with the mean number of drinks/day or the drink-years. Conclusions: This cross-sectional multicenter study suggested a possible minor role for smoking in worsening disease progression. A possible interaction with alcohol drinking was suggested. Full article

(This article belongs to the Section Medical Research)

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25 pages, 1203 KiB

Open AccessReview

Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences

by Michela Rugolo, Claudia Zanna and Anna Maria Ghelli

Life 2021, 11(4), 351; https://doi.org/10.3390/life11040351 - 17 Apr 2021

Cited by 4 | Viewed by 3414

Abstract

The mitochondrial respiratory chain encompasses four oligomeric enzymatic complexes (complex I, II, III and IV) which, together with the redox carrier ubiquinone and cytochrome c, catalyze electron transport coupled to proton extrusion from the inner membrane. The protonmotive force is utilized by [...] Read more.

The mitochondrial respiratory chain encompasses four oligomeric enzymatic complexes (complex I, II, III and IV) which, together with the redox carrier ubiquinone and cytochrome c, catalyze electron transport coupled to proton extrusion from the inner membrane. The protonmotive force is utilized by complex V for ATP synthesis in the process of oxidative phosphorylation. Respiratory complexes are known to coexist in the membrane as single functional entities and as supramolecular aggregates or supercomplexes (SCs). Understanding the assembly features of SCs has relevant biomedical implications because defects in a single protein can derange the overall SC organization and compromise the energetic function, causing severe mitochondrial disorders. Here we describe in detail the main types of SCs, all characterized by the presence of complex III. We show that the genetic alterations that hinder the assembly of Complex III, not just the activity, cause a rearrangement of the architecture of the SC that can help to preserve a minimal energetic function. Finally, the major metabolic disturbances associated with severe SCs perturbation due to defective complex III are discussed along with interventions that may circumvent these deficiencies. Full article

(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)

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11 pages, 4931 KiB

Open AccessArticle

The Optimal Application of Medium Potency Topical Corticosteroids in Preventing Laser-Induced Inflammatory Responses—An Animal Study

by Kuang-Ling Ou, Chia-Cheng Wen, Ching-Ya Lan, Yu-An Chen, Chih-Hsin Wang and Yi-Wen Wang

Life 2021, 11(4), 350; https://doi.org/10.3390/life11040350 - 17 Apr 2021

Cited by 7 | Viewed by 3850

Abstract

Background: During ablative fractional resurfacing (AFR) laser therapy, thermal damage to the skin is inevitable, resulting in inflammatory responses and small wounds. Corticosteroids are known for their anti-inflammatory effect. However, inappropriate application of corticosteroids carries the risk of delayed wound healing. Therefore, we [...] Read more.

Background: During ablative fractional resurfacing (AFR) laser therapy, thermal damage to the skin is inevitable, resulting in inflammatory responses and small wounds. Corticosteroids are known for their anti-inflammatory effect. However, inappropriate application of corticosteroids carries the risk of delayed wound healing. Therefore, we aimed to find the optimal administration route, timing, and duration of medium potency corticosteroid treatment to prevent AFR laser-induced inflammatory responses and to minimize the risk of delayed wound healing. Methods: We determined the anti-inflammatory efficacy of corticosteroids by skin erythema and tissue biopsies on C57BL/6 mice. Wound healing was evaluated by crust area and epithelial gap. Finally, Masson’s trichrome stain and α-SMA immunohistochemistry stain were used to analyze scar contracture. Results: Our results demonstrated that one dose of medium-potency topical corticosteroid applied immediately after AFR laser treatment could prevent erythema effectively with minimal disruption to wound healing. Notably, when more than one dose was administered, wound healing was delayed and scar contracture was aggravated by the application of medium-potency topical corticosteroids in a dosage-dependent manner. Conclusion: Our findings suggested that single-dose medium-potency topical corticosteroids could potentially improve AFR laser-induced acute inflammatory responses in clinical applications. Full article

(This article belongs to the Special Issue Frontiers of Dermatological Research)

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18 pages, 350 KiB

Open AccessReview

Definition of Sarcopenia in Chronic Liver Disease

by Seong Wan Son, Do Seon Song, U Im Chang and Jin Mo Yang

Life 2021, 11(4), 349; https://doi.org/10.3390/life11040349 - 16 Apr 2021

Cited by 23 | Viewed by 3818

Abstract

Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend [...] Read more.

Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend the use of various tools and tests to assess muscle properties and performance. These measurement tools have also been applied in patients with CLD and have been useful for predicting prognosis. However, sarcopenia and its diagnostic criteria specific to patients with CLD have not yet been clearly defined. In addition, fluid retention and body composition should be considered when sarcopenia is assessed in patients with CLD. This review aims to introduce definitions of sarcopenia and diagnostic tools used in patients with CLD. Full article

(This article belongs to the Special Issue Sarcopenia and Liver Disease: Current and Future Perspectives)

39 pages, 7240 KiB

Open AccessReview

Andrographis paniculata (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy

by Sanower Hossain, Zannat Urbi, Hidayah Karuniawati, Ramisa Binti Mohiuddin, Ahmed Moh Qrimida, Akrm Mohamed Masaud Allzrag, Long Chiau Ming, Ester Pagano and Raffaele Capasso

Life 2021, 11(4), 348; https://doi.org/10.3390/life11040348 - 16 Apr 2021

Cited by 158 | Viewed by 24955

Abstract

Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, [...] Read more.

Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, derived from A. paniculata, can inhibit invasive microbes virulence factors and regulate the host immunity. Controlled clinical trials revealed that A. paniculata treatment is safe and efficacious for acute respiratory tract infections like common cold and sinusitis. Hence, A. paniculata, mainly andrographolide, could be considered as an excellent candidate for antimicrobial drug development. Considering the importance, medicinal values, and significant role as antimicrobial agents, this study critically evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation. A critical evaluation of the secondary metabolites with the aim of identifying pure compounds that possess antimicrobial functions has further added significant values to this study. Notwithstanding that A. paniculata is a promising source of antimicrobial agents and safe treatment for IDs, further empirical research is warranted. Full article

(This article belongs to the Special Issue Therapeutic Potential of Traditional Medicinal Plants and their Bioactive Products)

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8 pages, 235 KiB

Open AccessArticle

Clinical Features of Patients with Home Isolation Sars-Cov-2 Infection: A Multicenter Retrospective Study in Southern Italy

by Mariantonietta Pisaturo, Giulia De Angelis, Paolo Maggi, Vincenzo Sangiovanni, Fabio Giuliano Numis, Ivan Gentile, Alfonso Masullo, Carolina Rescigno, Giosuele Calabria, Angelo Salomone Megna, Michele Gambardella, Elio Manzillo, Giancarlo Giolitto, Annamaria Rossomando, Antonio Riccardo Buonomo, Margherita Macera, Vincenzo Messina, Antonio Pagano, Raffaella Pisapia, Nunzia Farella, Giorgio Bosso, Nicola Coppola and CoviCam Group Show full author list Hide full author list

Life 2021, 11(4), 347; https://doi.org/10.3390/life11040347 - 16 Apr 2021

Cited by 3 | Viewed by 2319

Abstract

To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units [...] Read more.

To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O₂) therapy and those with a severe infection if hospitalized and required O₂ therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; <0.01) and were younger (median age 45 years (IQR:19) vs. 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs. 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs. 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94–0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54–0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management. Full article

(This article belongs to the Special Issue The New Challenges in Infectious Diseases)

19 pages, 5679 KiB

Open AccessArticle

Behavior of Chemokine Receptor 6 (CXCR6) in Complex with CXCL16 Soluble form Chemokine by Molecular Dynamic Simulations: General Protein‒Ligand Interaction Model and 3D-QSAR Studies of Synthetic Antagonists

by Giovanny Aguilera-Durán and Antonio Romo-Mancillas

Life 2021, 11(4), 346; https://doi.org/10.3390/life11040346 - 15 Apr 2021

Cited by 8 | Viewed by 4800

Abstract

The CXCR6‒CXCL16 axis is involved in several pathological processes, and its overexpression has been detected in different types of cancer, such as prostate, breast, ovary, and lung cancer, along with schwannomas, in which it promotes invasion and metastasis. Moreover, this axis is involved [...] Read more.

The CXCR6‒CXCL16 axis is involved in several pathological processes, and its overexpression has been detected in different types of cancer, such as prostate, breast, ovary, and lung cancer, along with schwannomas, in which it promotes invasion and metastasis. Moreover, this axis is involved in atherosclerosis, type 1 diabetes, primary immune thrombocytopenia, vitiligo, and other autoimmune diseases, in which it is responsible for the infiltration of different immune system cells. The 3D structure of CXCR6 and CXCL16 has not been experimentally resolved; therefore, homology modeling and molecular dynamics simulations could be useful for the study of this signaling axis. In this work, a homology model of CXCR6 and a soluble form of CXCL16 (CXCR6‒CXCL16s) are reported to study the interactions between CXCR6 and CXCL16s through coarse-grained molecular dynamics (CG-MD) simulations. CG-MD simulations showed the two activation steps of CXCR6 through a decrease in the distance between the chemokine and the transmembrane region (TM) of CXCR6 and transmembrane rotational changes and polar interactions between transmembrane segments. The polar interactions between TM3, TM5, and TM6 are fundamental to functional conformation and the meta-active state of CXCR6. The interactions between D77-R280 and T243-TM7 could be related to the functional conformation of CXCR6; alternatively, the interaction between Q195-Q244 and N248 could be related to an inactive state due to the loss of this interaction, and an arginine cage broken in the presence of CXCL16s allows the meta-active state of CXCR6. A general protein‒ligand interaction supports the relevance of TM3‒TM5‒TM6 interactions, presenting three relevant pharmacophoric features: HAc (H-bond acceptor), HDn (H-bond donator), and Hph (hydrophobic), distributed around the space between extracellular loops (ECLs) and TMs. The HDn feature is close to TM3 and TM6; likewise, the HAc and Hph features are close to ECL1 and ECL2 and could block the rotation and interactions between TM3‒TM6 and the interactions of CXCL16s with the ECLs. Tridimensional quantitative structure-activity relationships (3D-QSAR) models show that the positive steric (VdW) and electrostatic fields coincide with the steric and positive electrostatic region of the exo-azabicyclo[3.3.1]nonane scaffold in the best pIC50 ligands. This substructure is close to the E274 residue and therefore relevant to the activity of CXCR6. These data could help with the design of new molecules that inhibit chemokine binding or antagonize the receptor based on the activation mechanism of CXCR6 and provoke a decrease in chemotaxis caused by the CXCR6‒CXCL16 axis. Full article

(This article belongs to the Special Issue Advances in G Protein-Coupled Receptors Biophysical and Medicinal Chemistry)

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16 pages, 2218 KiB

Open AccessReview

Early Prevention of Atherosclerosis: Detection and Management of Hypercholesterolaemia in Children and Adolescents

by Cristina Pederiva, Maria Elena Capra, Claudia Viggiano, Valentina Rovelli, Giuseppe Banderali and Giacomo Biasucci

Life 2021, 11(4), 345; https://doi.org/10.3390/life11040345 - 14 Apr 2021

Cited by 27 | Viewed by 3937

Abstract

Coronary heart disease (CHD) is the main cause of death and morbidity in the world. There is a strong evidence that the atherosclerotic process begins in childhood and that hypercholesterolaemia is a CHD major risk factor. Hypercholesterolaemia is a modifiable CHD risk factor [...] Read more.

Coronary heart disease (CHD) is the main cause of death and morbidity in the world. There is a strong evidence that the atherosclerotic process begins in childhood and that hypercholesterolaemia is a CHD major risk factor. Hypercholesterolaemia is a modifiable CHD risk factor and there is a tracking of hypercholesterolaemia from birth to adulthood. Familial hypercholesterolaemia (FH) is the most common primitive cause of hypercholesterolaemia, affecting 1:200–250 individuals. Early detection and treatment of hypercholesterolaemia in childhood can literally “save decades of life”, as stated in the European Atherosclerosis Society Consensus. Multiple screening strategies have been proposed. In 2008, the American Academy of Pediatrics published the criteria for targeted screening, while some expert panels recommend universal screening particularly in the young, although cost effectiveness has not been fully analysed. Blood lipid profile evaluation [total cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C) and triglycerides] is the first step. It has to be ideally performed between two and ten years of age. Hypercholesterolaemia has to be confirmed with a second sample and followed by the detection of family history for premature (before 55 years in men and 60 years in women) or subsequent cardio-vascular events and/or hypercholesterolaemia in 1st and 2nd degree relatives. The management of hypercholesterolaemia in childhood primarily involves healthy lifestyle and a prudent low-fat diet, emphasising the benefits of the Mediterranean diet. Statins are the cornerstone of the drug therapy approved in USA and in Europe for use in children. Ezetimibe or bile acid sequestrants may be required to attain LDL-C goal in some patients. Early identification of children with severe hypercholesterolaemia or with FH is important to prevent atherosclerosis at the earliest stage of development, when maximum benefit can still be obtained via lifestyle adaptations and therapy. The purpose of our review is to highlight the importance of prevention and treatment of hypercholesterolaemia starting from the earliest stages of life. Full article

(This article belongs to the Special Issue Pediatric Nutrition for a Healthy Life)

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15 pages, 3896 KiB

Open AccessArticle

Evaluation of Conserved RNA Secondary Structures within and between Geographic Lineages of Zika Virus

by Kevin Nicolas Calderon, Johan Fabian Galindo and Clara Isabel Bermudez-Santana

Life 2021, 11(4), 344; https://doi.org/10.3390/life11040344 - 14 Apr 2021

Cited by 2 | Viewed by 2930

Abstract

Zika virus (ZIKV), without a vaccine or an effective treatment approved to date, has globally spread in the last century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in recent years, causing epidemics with greater infectivity, tropism [...] Read more.

Zika virus (ZIKV), without a vaccine or an effective treatment approved to date, has globally spread in the last century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in recent years, causing epidemics with greater infectivity, tropism towards new tissues and other related symptoms as a product of various emergent ZIKV–host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, the genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons have barely been studied. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 410 complete genomes in a phylogenomic scanning were used to study the conservation of structured RNAs. Our results show the contemporary landscape of conserved structured regions with unique conserved structured regions in clades or in lineages within circulating ZIKV strains. We propose these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that lead to ZIKV populations to acquire nucleotide substitutions, which is evidence of the local structure genome differentiation. Full article

(This article belongs to the Special Issue Open Science Phyloinformatics: Resources, Methods, and Analyses 2021)

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14 pages, 1236 KiB

Open AccessArticle

DUAL-tDCS Treatment over the Temporo-Parietal Cortex Enhances Writing Skills: First Evidence from Chronic Post-Stroke Aphasia

by Francesca Pisano, Carlo Caltagirone, Chiara Incoccia and Paola Marangolo

Life 2021, 11(4), 343; https://doi.org/10.3390/life11040343 - 14 Apr 2021

Cited by 5 | Viewed by 3057

Abstract

The learning of writing skills involves the re-engagement of previously established independent procedures. Indeed, the writing deficit an adult may acquire after left hemispheric brain injury is caused by either an impairment to the lexical route, which processes words as a whole, to [...] Read more.

The learning of writing skills involves the re-engagement of previously established independent procedures. Indeed, the writing deficit an adult may acquire after left hemispheric brain injury is caused by either an impairment to the lexical route, which processes words as a whole, to the sublexical procedure based on phoneme-to-grapheme conversion rules, or to both procedures. To date, several approaches have been proposed for writing disorders, among which, interventions aimed at restoring the sub-lexical procedure were successful in cases of severe agraphia. In a randomized double-blind crossover design, fourteen chronic Italian post-stroke aphasics underwent dual transcranial direct current stimulation (tDCS) (20 min, 2 mA) with anodal and cathodal current simultaneously placed over the left and right temporo-parietal cortex, respectively. Two different conditions were considered: (1) real, and (2) sham, while performing a writing task. Each experimental condition was performed for ten workdays over two weeks. After real stimulation, a greater amelioration in writing with respect to the sham was found. Relevantly, these effects generalized to different language tasks not directly treated. This evidence suggests, for the first time, that dual tDCS associated with training is efficacious for severe agraphia. Our results confirm the critical role of the temporo-parietal cortex in writing skills. Full article

(This article belongs to the Special Issue Brain Function, Dysfunction and Post-Damage Reorganization, Two Decades of Research)

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20 pages, 7513 KiB

Open AccessEditor’s ChoiceReview

The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

by Giorgio Bernardi

Life 2021, 11(4), 342; https://doi.org/10.3390/life11040342 - 13 Apr 2021

Cited by 8 | Viewed by 3611

Abstract

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin [...] Read more.

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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10 pages, 240 KiB

Open AccessArticle

Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?

by Małgorzata Kałużna, Krzysztof Pawlaczyk, Krzysztof Schwermer, Krzysztof Hoppe, Aisha Yusuf Ibrahim, Magdalena Czlapka-Matyasik, Elżbieta Wrotkowska, Katarzyna Ziemnicka, Andrzej Oko and Marek Ruchała

Life 2021, 11(4), 341; https://doi.org/10.3390/life11040341 - 12 Apr 2021

Cited by 4 | Viewed by 2658

Abstract

Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and [...] Read more.

Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. Results: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = −0.319, p = 0.009; r = −0.341, p = 0.005; r = −0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). Conclusions: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

16 pages, 2873 KiB

Open AccessArticle

Cross-Validation of Next-Generation Sequencing Technologies for Diagnosis of Chromosomal Mosaicism and Segmental Aneuploidies in Preimplantation Embryos Model

by Anil Biricik, Ettore Cotroneo, Maria Giulia Minasi, Pier Francesco Greco, Sara Bono, Matteo Surdo, Federica Lecciso, Mariateresa Sessa, Francesco Fiorentino, Francesca Spinella and Ermanno Greco

Life 2021, 11(4), 340; https://doi.org/10.3390/life11040340 - 12 Apr 2021

Cited by 10 | Viewed by 3560

Abstract

Detection of mosaic embryos is crucial to offer more possibilities of success to women undergoing in vitro fertilization (IVF) treatment. Next Generation Sequencing (NGS)-based preimplantation genetic testing are increasingly used for this purpose since their higher capability to detect chromosomal mosaicism in human [...] Read more.

Detection of mosaic embryos is crucial to offer more possibilities of success to women undergoing in vitro fertilization (IVF) treatment. Next Generation Sequencing (NGS)-based preimplantation genetic testing are increasingly used for this purpose since their higher capability to detect chromosomal mosaicism in human embryos. In the recent years, new NGS systems were released, however their performance for chromosomal mosaicism are variable. We performed a cross-validation analysis of two different NGS platforms in order to assess the feasibility of these techniques and provide standard parameters for the detection of such aneuploidies. The study evaluated the performance of Miseq^TM Veriseq (Illumina, San Diego, CA, USA) and Ion Torrent Personal Genome Machine PGM^TM ReproSeq (Thermo Fisher, Waltham, MA, USA) for the detection of whole and segmental mosaic aneuploidies. Reconstructed samples with known percentage of mosaicism were analyzed with both platforms and sensitivity and specificity were determined. Both platforms had high level of specificity and sensitivity with a Limit Of Detection (LOD) at ≥30% of mosaicism and a showed a ≥5.0 Mb resolution for segmental abnormalities. Our findings demonstrated that NGS methodologies are capable of accurately detecting chromosomal mosaicism and segmental aneuploidies. The knowledge of LOD for each NGS platform has the potential to reduce false-negative and false-positive diagnoses when applied to detect chromosomal mosaicism in a clinical setting. Full article

(This article belongs to the Special Issue The Increasing Role of Next Generation Sequencing Methods in Mutation Analysis)

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13 pages, 2372 KiB

Open AccessArticle

Evaluation of the Impact of Different Pain Medication and Proton Pump Inhibitors on the Osteogenic Differentiation Potential of hMSCs Using ^99mTc-HDP Labelling

by Tobias Grossner, Uwe Haberkorn and Tobias Gotterbarm

Life 2021, 11(4), 339; https://doi.org/10.3390/life11040339 - 11 Apr 2021

Cited by 4 | Viewed by 2393

Abstract

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce [...] Read more.

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive ^99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential. Full article

(This article belongs to the Section Radiobiology and Nuclear Medicine)

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11 pages, 1258 KiB

Open AccessArticle

Generation of Antibodies against Foot-and-Mouth-Disease Virus Capsid Protein VP4 Using Hepatitis B Core VLPs as a Scaffold

by Jessica Swanson, Rennos Fragkoudis, Philippa C. Hawes, Joseph Newman, Alison Burman, Anusha Panjwani, Nicola J. Stonehouse and Tobias J. Tuthill

Life 2021, 11(4), 338; https://doi.org/10.3390/life11040338 - 11 Apr 2021

Cited by 6 | Viewed by 3469

Abstract

The picornavirus foot-and-mouth disease virus (FMDV) is the causative agent of the economically important disease of livestock, foot-and-mouth disease (FMD). VP4 is a highly conserved capsid protein, which is important during virus entry. Previous published work has shown that antibodies targeting the N-terminus [...] Read more.

The picornavirus foot-and-mouth disease virus (FMDV) is the causative agent of the economically important disease of livestock, foot-and-mouth disease (FMD). VP4 is a highly conserved capsid protein, which is important during virus entry. Previous published work has shown that antibodies targeting the N-terminus of VP4 of the picornavirus human rhinovirus are broadly neutralising. In addition, previous studies showed that immunisation with the N-terminal 20 amino acids of enterovirus A71 VP4 displayed on the hepatitis B core (HBc) virus-like particles (VLP) can induce cross-genotype neutralisation. To investigate if a similar neutralising response against FMDV VP4 could be generated, HBc VLPs displaying the N-terminus of FMDV VP4 were designed. The N-terminal 15 amino acids of FMDV VP4 was inserted into the major immunodominant region. HBc VLPs were also decorated with peptides of the N-terminus of FMDV VP4 attached using a HBc-spike binding tag. Both types of VLPs were used to immunise mice and the resulting serum was investigated for VP4-specific antibodies. The VLP with VP4 inserted into the spike, induced VP4-specific antibodies, however the VLPs with peptides attached to the spikes did not. The VP4-specific antibodies could recognise native FMDV, but virus neutralisation was not demonstrated. This work shows that the HBc VLP presents a useful tool for the presentation of FMDV capsid epitopes. Full article

(This article belongs to the Special Issue Capsid Protein)

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Open AccessArticle

Serum Adropin Levels in Patients on Hemodialysis

by Dijana Boric-Skaro, Maja Mizdrak, Mirko Luketin, Dinko Martinovic, Daria Tokic, Marino Vilovic, Daniela Supe-Domic, Tina Ticinovic Kurir and Josko Bozic

Life 2021, 11(4), 337; https://doi.org/10.3390/life11040337 - 11 Apr 2021

Cited by 11 | Viewed by 2961

Abstract

Adropin is a novel pleotropic peptide involved in energy homeostasis, with possible contribution to cardiovascular protection through production of nitric oxide and subsequent blood pressure regulation. Given that patients undergoing hemodialysis (HD) are related with high cardiovascular risk, hyperlipidemia, chronic low-grade inflammation, and [...] Read more.

Adropin is a novel pleotropic peptide involved in energy homeostasis, with possible contribution to cardiovascular protection through production of nitric oxide and subsequent blood pressure regulation. Given that patients undergoing hemodialysis (HD) are related with high cardiovascular risk, hyperlipidemia, chronic low-grade inflammation, and malnutrition the aim of our study was to investigate serum adropin levels in HD patients to evaluate possible associations with nutritional status and other relevant clinical and laboratory parameters. The study included 70 patients on HD and 60 healthy controls. Serum adropin levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. Serum adropin levels were significantly lower in the HD group compared to the control group (2.20 ± 0.72 vs. 4.05 ± 0.93 ng/mL, p < 0.001). Moreover, there was a significant negative correlation with malnutrition-inflammation score (r = −0.476, p < 0.001), dialysis malnutrition score (r = −0.350, p = 0.003), HD duration (r = −0.305, p = 0.010), and high sensitivity C-reactive protein (hsCRP) (r = −0.646, p < 0.001). Additionally, there was a significant negative correlation between adropin levels and pre-dialysis systolic (r = −0.301, p = 0.011) and diastolic blood pressure (r = −0.299, p = 0.011). These results are implying that adropin is potentially involved in the pathophysiological mechanisms of chronic kidney disease (CKD)/HD and its complications. However, future larger scale longitudinal studies need to further address it. Full article

(This article belongs to the Section Medical Research)

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Life, Volume 11, Issue 4 (April 2021) – 100 articles

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