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Life
Volume 11
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Life, Volume 11, Issue 3 (March 2021) – 89 articles

Cover Story (view full-size image): Autophagy, which is essential for the homeostasis and cell viability of ocular tissues, can be altered in ocular pathologies. In glaucoma, autophagy is activated at the onset of the disease in response to elevated intraocular pressure, but if it becomes chronic, autophagy decreases and promotes the pathogenesis and progression of glaucoma. Alterations in autophagy in lens fibres decrease their transparency and lead to the development of cataracts. Autophagy is responsible for the defence of the RPE against damage, but under conditions of excessive metabolic stress, autophagic activity is altered and leads to damage in diabetic retinopathy. In AMD, autophagy in RPE cells is decreased, showing that it is closely related to AMD pathogenesis. Therefore, regulation and modulation of autophagy could be a potential therapy for the treatment of ocular pathologies. View this paper
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11 pages, 1370 KiB  
Article
Sex Differences on Mitotane Concentration and Treatment Outcome in Patients with Adrenocortical Carcinoma
by Sarah Allegra, Soraya Puglisi, Irene Brescia, Francesco Chiara, Vittoria Basile, Anna Calabrese, Giuseppe Reimondo and Silvia De Francia
Life 2021, 11(3), 266; https://doi.org/10.3390/life11030266 - 23 Mar 2021
Cited by 7 | Viewed by 2549
Abstract
(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To [...] Read more.
(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p′-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p′-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology. Full article
(This article belongs to the Special Issue Gender-Specific Medicine and Pharmacology)
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13 pages, 1074 KiB  
Article
Benefits of Binaural Integration in Cochlear Implant Patients with Single-Sided Deafness and Residual Hearing in the Implanted Ear
by Artur Lorens, Anita Obrycka, Piotr Henryk Skarzynski and Henryk Skarzynski
Life 2021, 11(3), 265; https://doi.org/10.3390/life11030265 - 23 Mar 2021
Cited by 6 | Viewed by 2452
Abstract
The purpose of the study is to gauge the benefits of binaural integration effects (redundancy and squelch) due to preserved low-frequency residual hearing in the implanted ear of cochlear implant users with single-sided deafness. There were 11 cochlear implant users (age 18–61 years [...] Read more.
The purpose of the study is to gauge the benefits of binaural integration effects (redundancy and squelch) due to preserved low-frequency residual hearing in the implanted ear of cochlear implant users with single-sided deafness. There were 11 cochlear implant users (age 18–61 years old) who had preserved low-frequency hearing in the implanted ear; they had a normal hearing or mild hearing loss in the contralateral ear. Patients were tested with monosyllabic words, under different spatial locations of speech and noise and with the cochlear implant activated and deactivated, in two listening configurations—one in which low frequencies in the implanted ear were masked and another in which they were unmasked. We also investigated how cochlear implant benefit due to binaural integration depended on unaided sound localization ability. Patients benefited from the binaural integration effects of redundancy and squelch only in the unmasked condition. Pearson correlations between binaural integration effects and unaided sound localization error showed significance only for squelch (r = −0.67; p = 0.02). Hearing preservation after cochlear implantation has considerable benefits because the preserved low-frequency hearing in the implanted ear contributes to binaural integration, presumably through the preserved temporal fine structure. Full article
(This article belongs to the Section Medical Research)
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13 pages, 2550 KiB  
Article
Primary Gastro-Intestinal Lymphoma and Gastro-Intestinal Adenocarcinoma: An Initial Study of CT Texture Analysis as Quantitative Biomarkers for Differentiation
by Lin Ding, Sisi Wu, Yaqi Shen, Xuemei Hu, Daoyu Hu, Ihab Kamel and Zhen Li
Life 2021, 11(3), 264; https://doi.org/10.3390/life11030264 - 23 Mar 2021
Viewed by 2136
Abstract
Background: To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC). Methods: A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. [...] Read more.
Background: To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC). Methods: A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. Histogram parameters of arterial and venous phases extracted from contrast enhanced modified discrete cosine transform (MDCT) images were compared between PGIL and GIAC by Mann–Whitney U tests. The optimal parameters for differentiating these two groups were obtained through receiver operating characteristic (ROC) curves and the area under the curve (AUC) was calculated. Results: Compared with GIAC, in arterial phase, PGIL had statistically higher 5th, 10th percentiles (p = 0.003 and 0.011) and statistically lower entropy (p = 0.001). In the venous phase, PGIL had statistically lower mean, median, 75th, 90th, 95th percentiles, and entropy (p = 0.036, 0.029, 0.007, 0.001 and 0.001, respectively). For differentiating PGIL from GIAC, V-median + A-5th percentile was an optimal parameter for combined diagnosis (AUC = 0.746, p < 0.0001), and the corresponding sensitivity and specificity were 81.7 and 64.8%, respectively. Conclusion: CT texture analysis could be useful for differential diagnosis of PGIL and GIAC. Full article
(This article belongs to the Section Medical Research)
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8 pages, 431 KiB  
Communication
Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B
by Tomoya Sano, Takumi Kawaguchi, Tatsuya Ide, Keisuke Amano, Reiichiro Kuwahara, Teruko Arinaga-Hino and Takuji Torimura
Life 2021, 11(3), 263; https://doi.org/10.3390/life11030263 - 23 Mar 2021
Cited by 5 | Viewed by 3305
Abstract
Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal [...] Read more.
Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB. Full article
(This article belongs to the Collection Research Updates in Chronic Kidney Disease)
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16 pages, 1383 KiB  
Review
Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
by Igor Pomytkin and Vsevolod Pinelis
Life 2021, 11(3), 262; https://doi.org/10.3390/life11030262 - 22 Mar 2021
Cited by 19 | Viewed by 5155
Abstract
Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead [...] Read more.
Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin. Full article
(This article belongs to the Special Issue Glutamate Receptors)
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9 pages, 265 KiB  
Article
Do Sex-Related Differences of Comorbidity Burden and/or In-Hospital Mortality Exist in Cancer Patients? A Retrospective Study in an Internal Medicine Setting
by Alfredo De Giorgi, Fabio Fabbian, Rosaria Cappadona, Ruana Tiseo, Christian Molino, Elisa Misurati, Edoardo Gambuti, Caterina Savriè, Benedetta Boari, Valeria Raparelli and Roberto Manfredini
Life 2021, 11(3), 261; https://doi.org/10.3390/life11030261 - 22 Mar 2021
Viewed by 2100
Abstract
Cancer represents important comorbidity, and data on outcomes are usually derived from selected oncologic units. Our aim was to evaluate possible sex-related differences and factors associated with in-hospital mortality (IHM) in a consecutive cohort of elderly patients with cancer admitted to internal medicine. [...] Read more.
Cancer represents important comorbidity, and data on outcomes are usually derived from selected oncologic units. Our aim was to evaluate possible sex-related differences and factors associated with in-hospital mortality (IHM) in a consecutive cohort of elderly patients with cancer admitted to internal medicine. We included all patients admitted to our department with a diagnosis of cancer during 2018. Based on the International Classification of Diseases, 9th Revision, Clinical Modification, demography, comorbidity burden, and diagnostic procedures were evaluated, with IHM as our outcome. We evaluated 955 subjects with cancer (23.9% of total hospital admissions), 42.9% were males, and the mean age was 76.4 ± 11.4 years. Metastatic cancer was diagnosed in 18.2%. The deceased group had a higher modified Elixhauser Index (17.6 ± 7.7 vs. 14 ± 7.3, p < 0.001), prevalence of cachexia (17.9% vs. 7.2%, p < 0.001), and presence of metastasis (27.8% vs. 16.3%, p = 0.001) than survivors. Females had a higher age (77.4 ± 11.4 vs. 75.5 ± 11.4, p = 0.013), and lower comorbidity (10.2 ± 5.9 vs. 12.0 ± 5.6, p < 0.001) than males. IHM was not significantly different among sex groups, but it was independently associated with cachexia and metastasis only in women. Comorbidities are highly prevalent in patients with cancer admitted to the internal medicine setting and are associated with an increased risk of all-cause mortality, especially in female elderly patients with advanced disease. Full article
(This article belongs to the Special Issue Gender-Specific Medicine and Pharmacology)
9 pages, 3015 KiB  
Article
Clinical Characteristics, Differential Diagnosis and Genetic Analysis of Concentric Retinitis Pigmentosa
by Mei Nakahara, Akio Oishi, Manabu Miyata, Hanako Ohashi Ikeda, Tomoko Hasegawa, Shogo Numa, Yuki Otsuka, Maho Oishi, Fumihiko Matsuda and Akitaka Tsujikawa
Life 2021, 11(3), 260; https://doi.org/10.3390/life11030260 - 22 Mar 2021
Cited by 5 | Viewed by 3538
Abstract
Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database [...] Read more.
Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution −0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p < 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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16 pages, 544 KiB  
Review
Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art
by Mariaconsiglia Calabrese, Marina Garofano, Roberta Palumbo, Paola Di Pietro, Carmine Izzo, Antonio Damato, Eleonora Venturini, Severino Iesu, Nicola Virtuoso, Andrea Strianese, Michele Ciccarelli, Gennaro Galasso and Carmine Vecchione
Life 2021, 11(3), 259; https://doi.org/10.3390/life11030259 - 21 Mar 2021
Cited by 37 | Viewed by 12619
Abstract
Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which [...] Read more.
Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees. Full article
(This article belongs to the Special Issue New Molecules and Mechanisms to Fight the Onset and Progression Cardiovascular Diseases—the Role of Oxidative Stress)
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10 pages, 244 KiB  
Article
The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature
by Mark Berman, Ronen Ben-Ami, Shlomo Berliner, Marina Anouk, Ilana Kaufman, Adi Broyde, Sara Borok and Ori Elkayam
Life 2021, 11(3), 258; https://doi.org/10.3390/life11030258 - 20 Mar 2021
Cited by 20 | Viewed by 3362
Abstract
Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results [...] Read more.
Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
15 pages, 3310 KiB  
Article
Toxicity and Anti-Proliferative Properties of Anisomeles indica Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos
by Nguyen T. Bich-Loan, Kieu Trung Kien, Nguyen Lai Thanh, Nguyen T. Kim-Thanh, Nguyen Quang Huy, Pham The-Hai, Marc Muller, Amandine Nachtergael, Pierre Duez and Nguyen Dinh Thang
Life 2021, 11(3), 257; https://doi.org/10.3390/life11030257 - 20 Mar 2021
Cited by 7 | Viewed by 4106
Abstract
In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. [...] Read more.
In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of BAX, CASPASE-8, and CASPASE-3 in the cells treated with AI-EtE at IC50 dose were 1.55-, 1.62-, and 2.45-fold higher than those in the control cells, respectively. Moreover, treatment with AI-EtE caused cell cycle arrest at the G1 phase in a p53-independent manner. Particularly, percentages of AI-EtE-treated cells in G1, S, G2/M were, respectively 85%, 6.7% and 6.4%; while percentages of control cells in G1, S, G2/M were 64%, 15% and 19%, respectively. Consistent with cell cycle arrest, the expressions of CDKN1A and CDNK2A in AI-EtE-treated cells were up-regulated 1.9- and 1.64-fold, respectively. Significantly, treatment with AI-EtE also decreased anchorage-independent growth of HeLa cells. In conclusion, we suggest that Anisomeles indica can be considered as a medicinal plant with a possible use against cervical cancer cells; however, the used dose should be carefully monitored, especially when applying to pregnant women. Full article
(This article belongs to the Section Pharmaceutical Science)
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11 pages, 321 KiB  
Review
Giardia and Cryptosporidium in Neo-Tropical Rodents and Marsupials: Is There Any Zoonotic Potential?
by Kegan Romelle Jones and Laura Tardieu
Life 2021, 11(3), 256; https://doi.org/10.3390/life11030256 - 20 Mar 2021
Cited by 3 | Viewed by 2471
Abstract
Cryptosporidiosis and giardiasis have been identified as emerging diseases in both developed and developing countries. Wildlife has been highlighted to play a major role in the spread of these diseases to humans. This review aims to highlight the research findings that relate to [...] Read more.
Cryptosporidiosis and giardiasis have been identified as emerging diseases in both developed and developing countries. Wildlife has been highlighted to play a major role in the spread of these diseases to humans. This review aims to highlight the research findings that relate to Cryptosporidium spp. and Giardia spp., with a focus on (1) parasitism of neo-tropical hystricomorphic rodents and marsupials from the genus Didelphis and (2) prevention and treatment strategies for humans and animals for the neo-tropical region. It was found that there are few studies conducted on neo-tropical rodent and marsupial species, but studies that were found illustrated the potential role these animals may play as zoonotic carriers of these two parasites for the neo-tropical region. Thus, it is recommended that further studies be done to assess the threat of protozoan parasites in neo-tropical wildlife to humans and domestic animals, and to further determine the most effective prophylaxis adapted for the unique conditions of the region. Full article
(This article belongs to the Special Issue Diarrheagenic Pathogens and Gastrointestinal Infections)
11 pages, 719 KiB  
Communication
The Case (or Not) for Life in the Venusian Clouds
by Dirk Schulze-Makuch
Life 2021, 11(3), 255; https://doi.org/10.3390/life11030255 - 20 Mar 2021
Cited by 11 | Viewed by 5956
Abstract
The possible detection of the biomarker of phosphine as reported by Greaves et al. in the Venusian atmosphere stirred much excitement in the astrobiology community. While many in the community are adamant that the environmental conditions in the Venusian atmosphere are too extreme [...] Read more.
The possible detection of the biomarker of phosphine as reported by Greaves et al. in the Venusian atmosphere stirred much excitement in the astrobiology community. While many in the community are adamant that the environmental conditions in the Venusian atmosphere are too extreme for life to exist, others point to the claimed detection of a convincing biomarker, the conjecture that early Venus was doubtlessly habitable, and any Venusian life might have adapted by natural selection to the harsh conditions in the Venusian clouds after the surface became uninhabitable. Here, I first briefly characterize the environmental conditions in the lower Venusian atmosphere and outline what challenges a biosphere would face to thrive there, and how some of these obstacles for life could possibly have been overcome. Then, I discuss the significance of the possible detection of phosphine and what it means (and does not mean) and provide an assessment on whether life may exist in the temperate cloud layer of the Venusian atmosphere or not. Full article
(This article belongs to the Special Issue Microbial Life in the Solar System)
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12 pages, 1731 KiB  
Article
Large Animal Model of Osteoporotic Defect Healing: An Alternative to Metaphyseal Defect Model
by Markus Rupp, Christoph Biehl, Deeksha Malhan, Fathi Hassan, Sameh Attia, Sebastian Rosch, Annemarie B. Schäfer, Erin McMahon, Marian Kampschulte, Christian Heiss and Thaqif El Khassawna
Life 2021, 11(3), 254; https://doi.org/10.3390/life11030254 - 19 Mar 2021
Cited by 3 | Viewed by 2786
Abstract
Osteoporosis is a common metabolic disorder diagnosed by lower bone density and higher risk of fracture. Fragility fractures because of osteoporosis are associated with high mortality rate. Deep understanding of fracture healing in osteoporosis is important for successful treatment. Therefore, the FDA approved [...] Read more.
Osteoporosis is a common metabolic disorder diagnosed by lower bone density and higher risk of fracture. Fragility fractures because of osteoporosis are associated with high mortality rate. Deep understanding of fracture healing in osteoporosis is important for successful treatment. Therefore, the FDA approved the use of small and large animal models for preclinical testing. This study investigated the clinical relevance of a fracture defect model in the iliac crest of the osteoporotic sheep model and its several advantages over other models. The osteoporosis was achieved using ovariectomy (OVX) in combination with diet deficiency (OVXD) and steroid administration (OVXDS). Fluorochrome was injected to examine the rate of bone remodelling and bone mineralization. The defect areas were collected and embedded in paraffin and polymethyl metha acrylate (PMMA) for histological staining. OVXDS showed significantly lower bone mineral density (BMD) and bone mineral content (BMC) at all time points. Furthermore, variations in healing patterns were noticed, while the control, OVX and OVXD showed complete healing after 8 months. Bone quality was affected mostly in the OVXDS group showing irregular trabecular network, lower cortical bone thickness and higher cartilaginous tissue at 8 months. The mineral deposition rate showed a declining pattern in the control, OVX, and OVXD from 5 months to 8 months. One the contrary, the OVXDS group showed an incremental pattern from 5 months to 8 months. The defect zone in osteoporotic animals showed impaired healing and the control showed complete healing after 8 months. This unique established model serves as a dual-purpose model and has several advantages: no intraoperative and postoperative complications, no need for fixation methods for biomaterial testing, and reduction in animal numbers, which comply with 3R principles by using the same animal at two different time points. Full article
(This article belongs to the Section Physiology and Pathology)
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15 pages, 548 KiB  
Article
Impact of a Nutrition-Related Community Intervention on the Quantity and Quality of Children’s School almuerzo
by Jenny Vilchis-Gil, Miguel Klünder-Klünder, Ximena Duque, Gloria Martínez-Andrade, Andrea Martínez-Almaráz, Brenda Beristain-Lujano and Samuel Flores-Huerta
Life 2021, 11(3), 253; https://doi.org/10.3390/life11030253 - 19 Mar 2021
Cited by 4 | Viewed by 3113
Abstract
Foods and beverages that schoolchildren carry in their lunchboxes have high energy values but lack plain water, fresh fruits and vegetables. A nutrition-related community intervention on the quantity and quality of school almuerzo was performed, in which four primary schools participated, as part [...] Read more.
Foods and beverages that schoolchildren carry in their lunchboxes have high energy values but lack plain water, fresh fruits and vegetables. A nutrition-related community intervention on the quantity and quality of school almuerzo was performed, in which four primary schools participated, as part of two groups: 225 children in the intervention group (IG) and 177 children in the control group (CG). The parents from the IG had access to a website where they could consult information on eating habits and physical activity or school almuerzo menus. They were sent weekly text messages on their mobile phones and attended in-person sessions. Anthropometric measurements and surveys were performed in both groups at the start of the study, as well as after 6 and 12 months. The school almuerzo was assessed by recording foods that the children brought in their lunchboxes. At baseline, 88% of children brought a school almuerzo, 37% fruit, 17% vegetables, 40% plain water and 50% sweet drinks. In both groups, 50% of children brought a school almuerzo with an energy value above the recommended value (>340 kcal) during follow-up; however, the percentage of children who brought sweet drinks decreased (p < 0.05), with sweet drinks contributing between 26% and 33% of the calories in the school almuerzo. In the IG, the quantity in milliliters of plain water increased at the end of the follow-up period (p = 0.044). From the point of view of food-and-beverage quantity and quality, school almuerzo were unhealthy for both groups. The intervention failed to increase the frequency with which parents provided children with school almuerzo or enhance the quality of the latter. Full article
(This article belongs to the Special Issue Pediatric Nutrition for a Healthy Life)
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11 pages, 2528 KiB  
Article
Mitochondrial DNA Analysis Clarifies Taxonomic Status of the Northernmost Snow Sheep (Ovis nivicola) Population
by Arsen V. Dotsev, Elisabeth Kunz, Veronika R. Kharzinova, Innokentiy M. Okhlopkov, Feng-Hua Lv, Meng-Hua Li, Andrey N. Rodionov, Alexey V. Shakhin, Taras P. Sipko, Dmitry G. Medvedev, Elena A. Gladyr, Vugar A. Bagirov, Gottfried Brem, Ivica Medugorac and Natalia A. Zinovieva
Life 2021, 11(3), 252; https://doi.org/10.3390/life11030252 - 18 Mar 2021
Cited by 6 | Viewed by 3680
Abstract
Currently, the intraspecific taxonomy of snow sheep (Ovis nivicola) is controversial and needs to be specified using DNA molecular genetic markers. In our previous work using whole-genome single nucleotide polymorphism (SNP) analysis, we found that the population inhabiting Kharaulakh Ridge was [...] Read more.
Currently, the intraspecific taxonomy of snow sheep (Ovis nivicola) is controversial and needs to be specified using DNA molecular genetic markers. In our previous work using whole-genome single nucleotide polymorphism (SNP) analysis, we found that the population inhabiting Kharaulakh Ridge was genetically different from the other populations of Yakut subspecies to which it was usually referred. Here, our study was aimed at the clarification of taxonomic status of Kharaulakh snow sheep using mitochondrial cytochrome b gene. A total of 87 specimens from five different geographic locations of Yakut snow sheep as well as 20 specimens of other recognized subspecies were included in this study. We identified 19 haplotypes, two of which belonged to the population from Kharaulakh Ridge. Median-joining network and Bayesian tree analyses revealed that Kharaulakh population clustered separately from all the other Yakut snow sheep. The divergence time between Kharaulakh population and Yakut snow sheep was estimated as 0.48 ± 0.19 MYA. Thus, the study of the mtDNA cytb sequences confirmed the results of genome-wide SNP analysis. Taking into account the high degree of divergence of Kharaulakh snow sheep from other groups, identified by both nuclear and mitochondrial DNA markers, we propose to classify the Kharaulakh population as a separate subspecies. Full article
(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)
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11 pages, 4031 KiB  
Article
A Novel Dipeptidyl Peptidase-4 Inhibitor DA-1229 Ameliorates Tubulointerstitial Fibrosis in Cyclosporine Nephrotoxicity in Mice
by Hye Sook Min, Ji Eun Lee, Jung Yeon Ghee, Young Sun Kang, Jin Joo Cha, Jee Young Han, Sang Youb Han and Dae Ryong Cha
Life 2021, 11(3), 251; https://doi.org/10.3390/life11030251 - 18 Mar 2021
Cited by 4 | Viewed by 2447
Abstract
Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal [...] Read more.
Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal disease in an experimental cyclosporine nephrotoxicity model. Chronic cyclosporine nephrotoxicity was induced in six-week-old male ICR mice by subcutaneous injections of CyA at a dose of 30 mg/kg for four weeks. Animals were treated with DA-1229 at a dose of 300 mg/kg per day in food for four weeks. Although DPP-4 activity did not increase in the kidneys of mice with induced cyclosporine nephrotoxicity, DA-1229 treatment significantly suppressed DPP-4 activity in both plasma and renal tissues. DPP-4 inhibition by DA-1229 led to significantly decreased albuminuria and urinary excretion of 8-isoprosatane. DPP-4 inhibition also substantially suppressed pro-inflammatory effects, profibrotic molecules, and macrophage infiltration, and led to the improvement in renal structural changes. Our results suggest that DPP-4 inhibition by DA-1229 provides renoprotective effects in an animal model of cyclosporine nephrotoxicity via antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. DPP-4 inhibition may be a useful new therapeutic approach for the management of progressive renal disease in cyclosporine nephrotoxicity. Full article
(This article belongs to the Collection Research Updates in Chronic Kidney Disease)
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16 pages, 736 KiB  
Review
Emerging Treatment Options for Sarcopenia in Chronic Liver Disease
by Yun Kim
Life 2021, 11(3), 250; https://doi.org/10.3390/life11030250 - 17 Mar 2021
Cited by 13 | Viewed by 6242
Abstract
Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and [...] Read more.
Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition. Full article
(This article belongs to the Special Issue Sarcopenia and Liver Disease: Current and Future Perspectives)
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13 pages, 1735 KiB  
Brief Report
Self-Reported Real-World Safety and Reactogenicity of COVID-19 Vaccines: A Vaccine Recipient Survey
by Alexander G. Mathioudakis, Murad Ghrew, Andrew Ustianowski, Shazaad Ahmad, Ray Borrow, Lida Pieretta Papavasileiou, Dimitrios Petrakis and Nawar Diar Bakerly
Life 2021, 11(3), 249; https://doi.org/10.3390/life11030249 - 17 Mar 2021
Cited by 90 | Viewed by 42656
Abstract
An online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups. This survey was launched in February 2021 and ran for 11 days. Recipients of a first COVID-19 vaccine dose ≥7 days prior to [...] Read more.
An online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups. This survey was launched in February 2021 and ran for 11 days. Recipients of a first COVID-19 vaccine dose ≥7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed. The survey was completed by 2002 respondents of whom 26.6% had a prior COVID-19 infection. A prior COVID-19 infection was associated with an increased risk of any side effect (risk ratio 1.08, 95% confidence intervals (1.05–1.11)), fever (2.24 (1.86–2.70)), breathlessness (2.05 (1.28–3.29)), flu-like illness (1.78 (1.51–2.10)), fatigue (1.34 (1.20–1.49)) and local reactions (1.10 (1.06–1.15)). It was also associated with an increased risk of severe side effects leading to hospital care (1.56 (1.14–2.12)). While mRNA vaccines were associated with a higher incidence of any side effect (1.06 (1.01–1.11)) compared with viral vector-based vaccines, these were generally milder (p < 0.001), mostly local reactions. Importantly, mRNA vaccine recipients reported a considerably lower incidence of systemic reactions (RR < 0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue and of side effects requiring hospital care (0.42 (0.31–0.58)). Our study confirms the findings of recent randomised controlled trials (RCTs) demonstrating that COVID-19 vaccines are generally safe with limited severe side effects. For the first time, our study links prior COVID-19 illness with an increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects but more local reactions. Full article
(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)
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15 pages, 1393 KiB  
Review
Aptamers, Riboswitches, and Ribozymes in S. cerevisiae Synthetic Biology
by Huanhuan Ge and Mario Andrea Marchisio
Life 2021, 11(3), 248; https://doi.org/10.3390/life11030248 - 17 Mar 2021
Cited by 16 | Viewed by 5812
Abstract
Among noncoding RNA sequences, riboswitches and ribozymes have attracted the attention of the synthetic biology community as circuit components for translation regulation. When fused to aptamer sequences, ribozymes and riboswitches are enabled to interact with chemicals. Therefore, protein synthesis can be controlled at [...] Read more.
Among noncoding RNA sequences, riboswitches and ribozymes have attracted the attention of the synthetic biology community as circuit components for translation regulation. When fused to aptamer sequences, ribozymes and riboswitches are enabled to interact with chemicals. Therefore, protein synthesis can be controlled at the mRNA level without the need for transcription factors. Potentially, the use of chemical-responsive ribozymes/riboswitches would drastically simplify the design of genetic circuits. In this review, we describe synthetic RNA structures that have been used so far in the yeast Saccharomyces cerevisiae. We present their interaction mode with different chemicals (e.g., theophylline and antibiotics) or proteins (such as the RNase III) and their recent employment into clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9 (CRISPR-Cas) systems. Particular attention is paid, throughout the whole paper, to their usage and performance into synthetic gene circuits. Full article
(This article belongs to the Special Issue Synthetic Genetic Elements, Devices, and Systems)
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10 pages, 489 KiB  
Article
Effects and Safety of Convalescent Plasma Administration in a Group of Polish Pediatric Patients with COVID-19: A Case Series
by Paweł Małecki, Kamil Faltin, Anna Mania, Katarzyna Mazur-Melewska, Agnieszka Cwalińska, Anna Zawadzka, Alicja Bukowska, Katarzyna Lisowska, Katarzyna Graniczna and Magdalena Figlerowicz
Life 2021, 11(3), 247; https://doi.org/10.3390/life11030247 - 17 Mar 2021
Cited by 8 | Viewed by 2735
Abstract
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined. The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation. Although it is usually mild, in [...] Read more.
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined. The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation. Although it is usually mild, in children with underlying chronic diseases, the course of SARS-CoV-2 infection may be very severe. We described a series of 13 pediatric patients (mean age 10.4 years, median 12) treated with convalescent plasma as a method of COVID-19 therapy. Medical history, with particular emphasis on comorbidities, clinical course, laboratory parameters, supportive treatment and virus elimination time, were analyzed. The mean hospitalization time was 22.6 days (median 20). The most common abnormalities included increased levels of C-reactive protein, D-dimer, and lymphopenia. Median time from symptom onset to convalescent plasma transfusion was 10.6 days (median 7 days). Six patients (46.2%) had a viral clearance on RT-PCR method from a nasopharyngeal swab within 3 days of transfusion, while in the remaining patients the mean elimination time was 12.1 days (median 6 days). Clinical improvement was achieved in all patients; no adverse effects were found in any of the cases. Convalescent plasma may be a promising treatment for COVID-19 in children. 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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10 pages, 1119 KiB  
Article
Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery
by Felix C. F. Schmitt, Martin Schneider, William Mathejczyk, Markus A. Weigand, Jane C. Figueiredo, Christopher I. Li, David Shibata, Erin M. Siegel, Adetunji T. Toriola, Cornelia M. Ulrich, Alexis B. Ulrich, Sébastien Boutin and Biljana Gigic
Life 2021, 11(3), 246; https://doi.org/10.3390/life11030246 - 16 Mar 2021
Cited by 11 | Viewed by 3017
Abstract
Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term [...] Read more.
Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery. Full article
(This article belongs to the Collection Antimicrobial Resistance)
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17 pages, 5525 KiB  
Article
Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro
by Daniil Shevyrev, Valeriy Tereshchenko, Elena Blinova, Nadezda Knauer, Ekaterina Pashkina, Alexey Sizikov and Vladimir Kozlov
Life 2021, 11(3), 245; https://doi.org/10.3390/life11030245 - 16 Mar 2021
Cited by 6 | Viewed by 2948
Abstract
Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory [...] Read more.
Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia. Full article
(This article belongs to the Special Issue New Insights into the Immunopathogenesis and Therapeutics of Rheumatic Diseases)
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9 pages, 794 KiB  
Communication
Autologous Matrix Induced Chondrogenesis (AMIC) Compared to Microfractures for Chondral Defects of the Talar Shoulder: A Five-Year Follow-Up Prospective Cohort Study
by Filippo Migliorini, Jörg Eschweiler, Nicola Maffulli, Hanno Schenker, Arne Driessen, Björn Rath and Markus Tingart
Life 2021, 11(3), 244; https://doi.org/10.3390/life11030244 - 16 Mar 2021
Cited by 17 | Viewed by 2986
Abstract
Introduction: Many procedures are available to manage cartilage defects of the talus, including microfracturing (MFx) and Autologous Matrix Induced Chondrogenesis (AMIC). Whether AMIC or MFx are equivalent for borderline sized defects of the talar shoulder is unclear. Thus, the present study compared the [...] Read more.
Introduction: Many procedures are available to manage cartilage defects of the talus, including microfracturing (MFx) and Autologous Matrix Induced Chondrogenesis (AMIC). Whether AMIC or MFx are equivalent for borderline sized defects of the talar shoulder is unclear. Thus, the present study compared the efficacy of primary isolated AMIC versus MFx for borderline sized focal unipolar chondral defects of the talar shoulder at midterm follow-up. Methods: Patients undergoing primary isolated AMIC or MFx for focal unipolar borderline sized chondral defects of the talar shoulder were recruited prospectively. For those patients who underwent AMIC, a type I/III collagen resorbable membrane was used. The outcomes of interest were: Visual Analogic Scale (VAS), Tegner Activity Scale, American Orthopedic Foot and Ankle Score (AOFAS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) was assessed by a blinded radiologist, who had not been involved in the clinical management of the patients. Data concerning complication rate and additional procedures were also collected. Results: The mean follow-up was 43.5 months. The mean age of the 70 patients at operation was 32.0 years, with a mean defect size of 2.7 cm2. The mean length of hospitalization was shorter in the MFx cohort (p = 0.01). No difference was found between the two cohorts in terms of length of prior surgery symptoms and follow-up, mean age and BMI, sex and side, and defect size. At a mean follow-up of 43.5 months, the AOFAS (p = 0.03), VAS (p = 0.003), and Tegner (p = 0.01) scores were greater in the AMIC group. No difference was found in the MOCART score (p = 0.08). The AMIC group evidenced lower rates of reoperation (p = 0.008) and failure (p = 0.003). Conclusion: At midterm follow-up, AMIC provides better results compared to MFx. Full article
(This article belongs to the Special Issue Focal Chondral Defects)
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20 pages, 1419 KiB  
Review
Regulation of Inflammation and Oxidative Stress by Formyl Peptide Receptors in Cardiovascular Disease Progression
by Valentina Maria Caso, Valentina Manzo, Tiziana Pecchillo Cimmino, Valeria Conti, Pio Caso, Gabriella Esposito, Vincenzo Russo, Amelia Filippelli, Rosario Ammendola and Fabio Cattaneo
Life 2021, 11(3), 243; https://doi.org/10.3390/life11030243 - 15 Mar 2021
Cited by 27 | Viewed by 5082
Abstract
G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide [...] Read more.
G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases. Full article
(This article belongs to the Special Issue New Molecules and Mechanisms to Fight the Onset and Progression Cardiovascular Diseases—the Role of Oxidative Stress)
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53 pages, 4522 KiB  
Review
Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology
by Salvatore Nesci, Fabiana Trombetti, Alessandra Pagliarani, Vittoria Ventrella, Cristina Algieri, Gaia Tioli and Giorgio Lenaz
Life 2021, 11(3), 242; https://doi.org/10.3390/life11030242 - 15 Mar 2021
Cited by 48 | Viewed by 6626
Abstract
Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled [...] Read more.
Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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11 pages, 3046 KiB  
Article
Hexane Extract of Chloranthus japonicus Increases Adipocyte Differentiation by Acting on Wnt/β-Catenin Signaling Pathway
by Ui Jeong Yun, Chu Won Nho, Kye Won Park and Dong Kwon Yang
Life 2021, 11(3), 241; https://doi.org/10.3390/life11030241 - 15 Mar 2021
Cited by 3 | Viewed by 2763
Abstract
Chloranthus japonicus has been heavily investigated for the treatment of various diseases. This paper attempts to show that Chloranthus japonicus can modulate adipocyte differentiation of preadipocytes. To establish this, we investigated the effects of Chloranthus japonicus extract in peroxisome proliferator-activated receptor γ (PPARγ) [...] Read more.
Chloranthus japonicus has been heavily investigated for the treatment of various diseases. This paper attempts to show that Chloranthus japonicus can modulate adipocyte differentiation of preadipocytes. To establish this, we investigated the effects of Chloranthus japonicus extract in peroxisome proliferator-activated receptor γ (PPARγ) expression, adipogenesis, and the underlying molecular mechanisms in C3H10T1/2 and 3T3-L1 cells. Our data showed that Chloranthus japonicus methanol extract increased lipid accumulation and promoted adipocyte differentiation. Further studies on the fractionation with various solvents led to the identification of Chloranthus japonicus hexane extract (CJHE) as the most potent inducer of adipocyte differentiation. CJHE consistently increased lipid accumulation and adipocyte marker expression including Pparγ and it acted during the early stages of adipocyte differentiation. Mechanistic studies revealed that CJHE and a Wnt inhibitor similarly stimulated adipogenesis and were active in Wnt-selective reporter assays. The effects of CJHE were inhibited by Wnt3a protein treatment and were significantly blunted in β-catenin-silenced cells, further suggesting that CJHE acted on Wnt pathways to promote adipogenesis. We also showed that Chloranthus japonicus extracts generated from different plant parts similarly promoted adipocyte differentiation. These results identified Chloranthus japonicus as a pro-adipogenic natural product and suggest its potential use in metabolic syndrome. Full article
(This article belongs to the Special Issue Therapeutic Potential of Traditional Medicinal Plants and their Bioactive Products)
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22 pages, 573 KiB  
Article
Use of Different Types of Biosorbents to Remove Cr (VI) from Aqueous Solution
by Eva Pertile, Tomáš Dvorský, Vojtěch Václavík and Silvie Heviánková
Life 2021, 11(3), 240; https://doi.org/10.3390/life11030240 - 14 Mar 2021
Cited by 27 | Viewed by 2750
Abstract
This article summarizes the results of a research study that was focused on the possibility of removing Cr (VI) from aqueous solution, using low-cost waste biomaterial in a batch mode. A set of seven biosorbents was used: Fomitopsis pinicola, a mixture of [...] Read more.
This article summarizes the results of a research study that was focused on the possibility of removing Cr (VI) from aqueous solution, using low-cost waste biomaterial in a batch mode. A set of seven biosorbents was used: Fomitopsis pinicola, a mixture of cones, peach stones, apricot stones, Juglans regia shells, orange peels, and Merino sheep wool. Three grain fractions (fr. 1/2, fr. 0.5/1.0, and fr. 0/0.5 mm) of biosorbents were studied. The aim was to find the most suitable biosorbent that can be tested with real samples. The influence of other factors on the course of biosorption was studied as well (chemical activation of the biosorbent, pH value, rotation speed during mixing, temperature, and the influence of biosorbent concentration). The use of chemical activation and adjustment of the pH to 1.1 to 2.0 make it possible to increase their sorption capacity and, for some biosorbents, to shorten the exposure times. Two kinetic models were used for the analysis of the experimental data, to explain the mechanism of adsorption and its possible speed control steps: pseudo-first and pseudo-second-order. The pseudo-second-order kinetic model seems to be the most suitable for the description of the experimental data. The thermodynamic parameters suggest that the biosorption was endothermic and spontaneous. In the biosorption equilibrium study, the adsorption data were described by using Langmuir and Freundlich adsorption isotherms. The Langmuir model was applicable to describe the adsorption data of all biosorbents. Both models are suitable for chemically treated sheep fleece and peach stones. Full article
(This article belongs to the Special Issue Microbial Degradation and Biosorbents)
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13 pages, 652 KiB  
Review
How Effective Is Auditory–Verbal Therapy (AVT) for Building Language Development of Children with Cochlear Implants? A Systematic Review
by Paris Binos, Elina Nirgianaki and George Psillas
Life 2021, 11(3), 239; https://doi.org/10.3390/life11030239 - 13 Mar 2021
Cited by 18 | Viewed by 11732
Abstract
This systematic review sheds light on the effectiveness of auditory–verbal therapy (AVT) outcomes in children with cochlear implants (CIs). The presented outcome is based on research findings from the last 10 years. The systematic review was designed based on the Preferred Reporting Items [...] Read more.
This systematic review sheds light on the effectiveness of auditory–verbal therapy (AVT) outcomes in children with cochlear implants (CIs). The presented outcome is based on research findings from the last 10 years. The systematic review was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Critical Appraisal of Treatment Evidence (CATE) checklist. Specific keywords were chosen based on the research question and searched on the PubMed database. All searched papers were analysed based on specific exclusion criteria and classified into four evidence levels. The results revealed that children who participated in AV therapy can achieve linguistic skills at the same level as their hearing peers. Voice quality seemed positively affected, placing young children with CIs in the normal range for receptive vocabulary development. In contrast, reading skills seemed less benefited. AV therapy seems to contribute to integration into mainstream society. Despite the recorded speech and language improvements of young children with CIs, the aim of AV therapy is still not fulfilled. AV therapy can be seen as the best clinical practice for young children with CIs till now, but the lack of well-controlled studies is undermining. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of ENT Diseases: Otological and Sinus Disorders)
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19 pages, 1766 KiB  
Review
Oligodendroglial Energy Metabolism and (re)Myelination
by Vanja Tepavčević
Life 2021, 11(3), 238; https://doi.org/10.3390/life11030238 - 13 Mar 2021
Cited by 22 | Viewed by 6399
Abstract
Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has [...] Read more.
Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease. Full article
(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)
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11 pages, 1597 KiB  
Article
A Relationship between NTP and Cell Extract Concentration for Cell-Free Protein Expression
by Katsuki Takahashi, Gaku Sato, Nobuhide Doi and Kei Fujiwara
Life 2021, 11(3), 237; https://doi.org/10.3390/life11030237 - 13 Mar 2021
Cited by 9 | Viewed by 3776
Abstract
The cell-free protein synthesis (CFPS) that synthesizes mRNA and protein from a template DNA has been featured as an important tool to emulate living systems in vitro. However, an obstacle to emulate living cells by CFPS is the loss of activity in the [...] Read more.
The cell-free protein synthesis (CFPS) that synthesizes mRNA and protein from a template DNA has been featured as an important tool to emulate living systems in vitro. However, an obstacle to emulate living cells by CFPS is the loss of activity in the case of usage of high concentration cell extracts. In this study, we found that a high concentration of NTP which inhibits in the case of lower concentration cell extract restored the loss of CFPS activity using high concentration cell extracts. The NTP restoration was independent of the energy regeneration system used, and NTP derivatives also restored the levels of CFPS using a high concentration cell extract. Experiments using dialysis mode of CFPS showed that continuous exchange of small molecule reduced levels of NTP requirement and improved reaction speed of CFPS using the high concentration of cell extract. These findings contribute to the development of a method to understand the condition of living cells by in vitro emulation, and are expected to lead to the achievement of the reconstitution of living cells from biomolecule mixtures. Full article
(This article belongs to the Special Issue Trends and Outlooks in Synthetic Biology: A Special Issue for Celebrating 10 Years of Life and Its Landmarks)
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