Life

Open AccessOpinion

Extending Validity of the Bacterial Cell Cycle Model through Thymine Limitation: A Personal View

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Life 2023, 13(4), 906; https://doi.org/10.3390/life13040906 (registering DOI) - 29 Mar 2023

The contemporary view of bacterial physiology was established in 1958 at the “Copenhagen School”, culminating a decade later in a detailed description of the cell cycle based on four parameters. This model has been subsequently supported by numerous studies, nicknamed BCD (The Bacterial [...] Read more.

The contemporary view of bacterial physiology was established in 1958 at the “Copenhagen School”, culminating a decade later in a detailed description of the cell cycle based on four parameters. This model has been subsequently supported by numerous studies, nicknamed BCD (The Bacterial Cell-Cycle Dogma). It readily explains, quantitatively, the coupling between chromosome replication and cell division, size and DNA content. An important derivative is the number of replication positions n, the ratio between the time C to complete a round of replication and the cell mass doubling time τ; the former is constant at any temperature and the latter is determined by the medium composition. Changes in cell width W are highly correlated to n through the equation for so-called nucleoid complexity NC (=(2ⁿ − 1)/(ln2

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n)), the amount of DNA per terC (i.e., chromosome) in genome equivalents. The narrow range of potential n can be dramatically extended using the method of thymine limitation of thymine-requiring mutants, which allows a more rigorous testing of the hypothesis that the nucleoid structure is the primary source of the signal that determines W during cell division. How this putative signal is relayed from the nucleoid to the divisome is still highly enigmatic. The aim of this Opinion article is to suggest the possibility of a new signaling function for nucleoid DNA. Full article

(This article belongs to the Special Issue Novel Principles and Methods in Bacterial Cell Cycle Physiology: Celebrating the Charles E. Helmstetter Prize in 2022)

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Open AccessReview

Neural Stem Cells as Potential Glioblastoma Cells of Origin

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Alba Loras

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Luis G. Gonzalez-Bonet

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Julia L. Gutierrez-Arroyo

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Conrado Martinez-Cadenas

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Maria Angeles Marques-Torrejon

Life 2023, 13(4), 905; https://doi.org/10.3390/life13040905 (registering DOI) - 29 Mar 2023

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults and it remains incurable. These tumors are very heterogeneous, resistant to cytotoxic therapies, and they show high rates of invasiveness. Therefore, patients face poor prognosis, and the survival rates remain very low. [...] Read more.

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults and it remains incurable. These tumors are very heterogeneous, resistant to cytotoxic therapies, and they show high rates of invasiveness. Therefore, patients face poor prognosis, and the survival rates remain very low. Previous research states that GBM contains a cell population with stem cell characteristics called glioma stem cells (GSCs). These cells are able to self-renew and regenerate the tumor and, therefore, they are partly responsible for the observed resistance to therapies and tumor recurrence. Recent data indicate that neural stem cells (NSCs) in the subventricular zone (SVZ) are the cells of origin of GBM, that is, the cell type acquiring the initial tumorigenic mutation. The involvement of SVZ-NSCs is also associated with GBM progression and recurrence. Identifying the cellular origin of GBM is important for the development of early detection techniques and the discovery of early disease markers. In this review, we analyze the SVZ-NSC population as a potential GBM cell of origin, and its potential role for GBM therapies. Full article

(This article belongs to the Special Issue Neural Stem Cells: Identity and Potential)

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Open AccessArticle

Influence of Extraction Techniques and Solvents on the Antioxidant and Biological Potential of Different Parts of Scorzonera undulata

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Life 2023, 13(4), 904; https://doi.org/10.3390/life13040904 - 29 Mar 2023

Abstract

The genus Scorzonera has various medicinal values. Species belonging to this genus were traditionally used as drugs or in food. The current study aimed to determine the phytochemical composition, antioxidant activity, and biological properties of the tuber, leaf, and flower of Scorzonera undulata [...] Read more.

The genus Scorzonera has various medicinal values. Species belonging to this genus were traditionally used as drugs or in food. The current study aimed to determine the phytochemical composition, antioxidant activity, and biological properties of the tuber, leaf, and flower of Scorzonera undulata extracts, collected from the southwest of Tunisia. Phenolic compounds from the three parts were extracted using two solvents (water and ethanol) and two extraction techniques (maceration and ultrasound). The total phenolic content was measured by the Folin–Ciocalteu assay. Furthermore, the chemical composition of Scorzonera undulata extract was also investigated by the LC-ESI–MS method using phenolic acid and flavonoid standards. The variation of the extraction methods induced a variation in the real potentialities of the three parts in terms of bioactive molecules. However, the aerial part of S. undulata (leaves and flowers) showed, in general, the highest phenolic contents. Twenty-five volatile compounds have been detected by GC-MS in S. undulata extracts; among them, fourteen were identified before derivatization. The DPPH test showed that the aerial part of the plant has a higher antioxidant activity compared to the tuber (25.06% at 50 µg/mL for the leaf ethanolic extract obtained by ultrasound extraction). For most biological activities (anti-Xanthine, anti-inflammatory, and antidiabetic (alpha-amylase and alpha-glucosidase)), the aerial parts (flowers and leaves) of the plant showed the highest inhibition than tubers. Full article

(This article belongs to the Special Issue Extraction, Characterization, and Application of Valuable Biologically Active Substances from Plants)

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Graphical abstract

Open AccessReview

Non-Viral Carriers for Nucleic Acids Delivery: Fundamentals and Current Applications

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Life 2023, 13(4), 903; https://doi.org/10.3390/life13040903 - 29 Mar 2023

Abstract

Over the past decades, non-viral DNA and RNA delivery systems have been intensively studied as an alternative to viral vectors. Despite the most significant advantage over viruses, such as the lack of immunogenicity and cytotoxicity, the widespread use of non-viral carriers in clinical [...] Read more.

Over the past decades, non-viral DNA and RNA delivery systems have been intensively studied as an alternative to viral vectors. Despite the most significant advantage over viruses, such as the lack of immunogenicity and cytotoxicity, the widespread use of non-viral carriers in clinical practice is still limited due to the insufficient efficacy associated with the difficulties of overcoming extracellular and intracellular barriers. Overcoming barriers by non-viral carriers is facilitated by their chemical structure, surface charge, as well as developed modifications. Currently, there are many different forms of non-viral carriers for various applications. This review aimed to summarize recent developments based on the essential requirements for non-viral carriers for gene therapy. Full article

(This article belongs to the Special Issue Microbiome-miRNAs Axis Role in Human Health and Disease)

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Open AccessArticle

Anatomical and Functional Outcomes after Endoresection and Adjuvant Ruthenium Brachytherapy for Uveal Melanoma: A Single-Center Experience

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Life 2023, 13(4), 902; https://doi.org/10.3390/life13040902 - 29 Mar 2023

Abstract

Purpose: To evaluate the anatomical and functional outcomes of endoresection and adjuvant ruthenium (Ru)-106 brachytherapy for uveal melanoma (UM). Methods: Retrospective case series of 15 UM patients (15 eyes) treated at our center (Careggi University Hospital, Florence). Results: Six patients (40%) were male [...] Read more.

Purpose: To evaluate the anatomical and functional outcomes of endoresection and adjuvant ruthenium (Ru)-106 brachytherapy for uveal melanoma (UM). Methods: Retrospective case series of 15 UM patients (15 eyes) treated at our center (Careggi University Hospital, Florence). Results: Six patients (40%) were male and nine were female (60%). The mean age of patients at the time of treatment was 61.6 years (±19.41). The mean BCVA at baseline was 20/50. In all cases UM originated from the choroid. The mean tumor thickness at baseline was 7.14 mm (±2.05), and the mean largest basal diameter was 11.2 mm (±1.92). A concurrent retinal detachment was diagnosed in 11 patients (73.3%). Two patients (13.3%) showed vitreous seeding at baseline. Eleven patients (73.3%) were treated with primary endoresection, while four patients (26.7%) were treated with a “salvage endoresection” after primary treatment failure (previous radiation treatment). The mean follow-up time was 28.9 months (±10.6). Thirteen out of fifteen patients were alive and showed no evidence of local recurrence or distance metastasis at the last follow-up visit. The treatment achieved local control of the disease in 14 out of 15 cases (93.3%). In one case, the patient underwent enucleation for disease recurrence. The overall survival rate at the end of the follow-up was 93.3%. The mean BCVA at last follow-up visit was 20/40. Treatment was well tolerated, without significant complications. Conclusions: Endoresection and adjuvant Ru-106 brachytherapy is a valuable conservative option for selected UM patients and can be used both as a primary treatment and as a salvage therapy. It can control melanoma and avoid enucleation, reduce radiation-related complications, and provide tumor tissue for chromosomal analysis and prognostic testing. Full article

(This article belongs to the Special Issue New Diagnostic and Therapeutic Developments in Eye Diseases)

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Open AccessCase Report

Ulceration and a White Lesion of the Tongue in a Male HIV Positive Patient: A Journey on the Avenue of Differential Diagnoses in Search of a Solution

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Manuela Arbune

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Monica-Daniela Padurariu-Covit

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Life 2023, 13(4), 901; https://doi.org/10.3390/life13040901 - 28 Mar 2023

Abstract

Oral lesions are early indicator of immunosuppression, leading to HIV new diagnoses. The type of oral lesions can reveal opportunistic diseases that are correlated with the severity of immune depletion. Highly active antiretroviral therapy decreases the incidence of opportunistic oral infections, whereas a [...] Read more.

Oral lesions are early indicator of immunosuppression, leading to HIV new diagnoses. The type of oral lesions can reveal opportunistic diseases that are correlated with the severity of immune depletion. Highly active antiretroviral therapy decreases the incidence of opportunistic oral infections, whereas a large variety of lesions are frequently experienced in people with HIV. Overlapping pathogenic mechanisms and multiple contributing etiologies are related to unusual, atypical oral lesions that are challenging in the clinical practice. We present a rare case of eosinophilic granuloma of the tongue in an older male HIV patient with severe immunosuppression due to the failure of antiretroviral treatment. Differential diagnoses considered squamous carcinoma, lymphoma, viral, fungal or bacterial infections and autoimmune disorders, as well as the influence of HIV immune disfunctions or the influence of cannabidiol use. The histopathologic and immunohistochemistry examination clarified the inflammatory reactive benign substrate of the lesion, although future survey of the oral lesions is essential. Full article

(This article belongs to the Special Issue Current Research on Dermatology: Pathology, Clinical Manifestation, Investigation and Therapy)

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Open AccessArticle

Neuroborreliosis and Post-Treatment Lyme Disease Syndrome: Focus on Children

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Agnieszka Myszkowska-Torz

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Magdalena Frydrychowicz

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Mateusz Tomaszewski

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Magdalena Figlerowicz

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Anna Mania

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Katarzyna Mazur-Melewska

Life 2023, 13(4), 900; https://doi.org/10.3390/life13040900 - 28 Mar 2023

Abstract

Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme [...] Read more.

Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1–2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The concentration of anti-VlsE IgG demonstrates a statistical significance for differences between the control and the study groups for each measurement period. Higher values of anti-VlsE IgG were observed in the study group, and the concentration decreased from the first measurement period to the next. The article emphasizes the importance of the long-term follow-up of children with neuroborreliosis. Full article

(This article belongs to the Special Issue Lyme Disease-An Incompletely Solved Puzzle)

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Open AccessArticle

Unbiased Quantitative Single-Cell Morphometric Analysis to Identify Microglia Reactivity in Developmental Brain Injury

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Life 2023, 13(4), 899; https://doi.org/10.3390/life13040899 - 28 Mar 2023

Abstract

Microglia morphological studies have been limited to the process of reviewing the most common characteristics of a group of cells to conclude the likelihood of a “pathological” milieu. We have developed an Imaris-software-based analytical pipeline to address selection and operator biases, enabling use [...] Read more.

Microglia morphological studies have been limited to the process of reviewing the most common characteristics of a group of cells to conclude the likelihood of a “pathological” milieu. We have developed an Imaris-software-based analytical pipeline to address selection and operator biases, enabling use of highly reproducible machine-learning algorithms to quantify at single-cell resolution differences between groups. We hypothesized that this analytical pipeline improved our ability to detect subtle yet important differences between groups. Thus, we studied the temporal changes in Iba1⁺ microglia-like cell (MCL) populations in the CA1 between P10–P11 and P18–P19 in response to intrauterine growth restriction (IUGR) at E12.5 in mice, chorioamnionitis (chorio) at E18 in rats and neonatal hypoxia–ischemia (HI) at P10 in mice. Sholl and convex hull analyses differentiate stages of maturation of Iba1⁺ MLCs. At P10–P11, IUGR or HI MLCs were more prominently ‘ameboid’, while chorio MLCs were hyper-ramified compared to sham. At P18–P19, HI MLCs remained persistently ‘ameboid’ to ‘transitional’. Thus, we conclude that this unbiased analytical pipeline, which can be adjusted to other brain cells (i.e., astrocytes), improves sensitivity to detect previously elusive morphological changes known to promote specific inflammatory milieu and lead to worse outcomes and therapeutic responses. Full article

(This article belongs to the Special Issue Diversifying and Strengthening Translational Animal Models of Newborn Brain Injuries)

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Open AccessArticle

Syndecan-1: From a Promising Novel Cardiac Biomarker to a Surrogate Early Predictor of Kidney and Liver Injury in Patients with Acute Heart Failure

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Radu-Stefan Miftode

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Irina-Iuliana Costache

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Daniela Constantinescu

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Ovidiu Mitu

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Amalia-Stefana Timpau

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Monica Hancianu

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Daniela-Anicuta Leca

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Ionela-Larisa Miftode

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Raul-Alexandru Jigoranu

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Alexandru-Florinel Oancea

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Mihai Stefan Cristian Haba

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Diandra Ioana Miftode

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Ionela-Lacramioara Serban

Life 2023, 13(4), 898; https://doi.org/10.3390/life13040898 - 28 Mar 2023

Abstract

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately [...] Read more.

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately reflect all the pathophysiological mechanisms involved in the progression of this pathology when determined independently. Therefore, the current paradigm tends to focus on a multi-marker approach for the risk stratification of patients with acute HF. Syndecan-1 is a less studied biomarker in cardiovascular diseases; its assessment in patients with acute HF being potentially able to reflect the myocardial pathological changes, such as fibrosis, inflammation, endothelial dysfunction or global wall stress. (2) Methods: We conducted a single center prospective study that enrolled 173 patients (120 patients admitted for acute HF, compared to 53 controls with stable chronic HF). A complete standardized clinical, echocardiography and laboratory evaluation was performed at admission, including serum samples for the determination of syndecan-1 by the enzyme-linked immunosorbent assay (ELISA) method. (3) Results: The serum concentration of syndecan-1 was significantly higher in patients with acute HF, compared to controls [121.4 (69.3–257.9) vs. 72.1 (41.4–135.8) ng/mL, p = 0.015]. Syndecan-1 was a significant predictor for the diagnosis of acute HF, expressed by an area under the curve (AUC) of 0.898, similar to NT-proBNP (AUC: 0.976) or cardiac troponin (AUC: 0.839). Moreover, syndecan-1 was independently associated with impaired kidney and liver function at admission, being also a predictor for early, subclinical organ dysfunction in patients with normal biological parameters at admission. When included in the multi-marker model, syndecan-1 levels influenced mortality more significantly than NT-proBNP or troponin. A multivariable regression including syndecan-1, NT-proBNP and troponin provided additional prognostic value compared to each independent biomarker. (4) Conclusions: Syndecan-1 can be considered a promising novel biomarker in acute HF, exhibiting adequate diagnostic and prognostic value. Additionally, syndecan-1 can be used as a surrogate biomarker for non-cardiac organ dysfunction, as its highs levels can accurately reflect early acute kidney and liver injury. Full article

(This article belongs to the Special Issue Ischemic Heart Disease in the Context of Different Comorbidities, Volume II)

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Open AccessArticle

Association between Inflammatory Bowel Disease and Subsequent Development of Restless Legs Syndrome and Parkinson’s Disease: A Retrospective Cohort Study of 35,988 Primary Care Patients in Germany

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Life 2023, 13(4), 897; https://doi.org/10.3390/life13040897 - 28 Mar 2023

Abstract

Background: In addition to the gastrointestinal symptoms, inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is associated with extraintestinal manifestations, including neurological disorders, which are gaining increasing attention due to a recently increased focus on the gut–brain axis. [...] Read more.

Background: In addition to the gastrointestinal symptoms, inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is associated with extraintestinal manifestations, including neurological disorders, which are gaining increasing attention due to a recently increased focus on the gut–brain axis. Here we aim to evaluate the association between IBD and restless legs syndrome (RLS) as well as Parkinson’s disease (PD) in a cohort of primary care patients in Germany. Methods: The study included 17,994 individuals with a diagnosis of IBD (7544 with CD and 10,450 with UC) and 17,994 propensity-score-matched individuals without IBD from the Disease Analyzer database (IQVIA). An initial diagnosis of RLS or PD was assessed as a function of IBD. Associations between CD and UC with RLS and PD were analyzed using Cox regression models. Results: During the 10-year observation period, 3.6% of CD patients vs. 1.9% of matched non-IBD pairs (p < 0.001) and 3.2% of UC patients vs. 2.7% of matched pairs (p < 0.001) were diagnosed with RLS. The results were confirmed by Cox regression analysis, which showed a significant association between UC (HR: 1.26; 95% CI: 1.02–1.55) and CD (HR: 1.60; 95% CI: 1.23–2.09) and subsequent RLS. The incidence of PD in IBD patients was not significantly increased. However, we observed a non-significant trend towards a higher incidence of PD in male patients with CD but not UC (HR: 1.55; 95%CI: 0.98–2.45, p = 0.064). Conclusions: The present analysis suggests a significant association between IBD and the subsequent development of RLS. These findings should stimulate further pathophysiological research and may eventually lead to specific screening measures in patients with IBD. Full article

(This article belongs to the Special Issue Trends and Outlooks in Neurogastroenterology)

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Open AccessCase Report

Embolization of Ruptured Infratentorial Pial AVM in Pregnancy

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Kamil Zeleňák

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Dušan Šalát

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Branislav Kolarovszki

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Egon Kurča

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Jana Zeleňáková

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Naci Koçer

Life 2023, 13(4), 896; https://doi.org/10.3390/life13040896 - 28 Mar 2023

Abstract

A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, AVM embolization was performed. Complete occlusion [...] Read more.

A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, AVM embolization was performed. Complete occlusion of the AVM was achieved by embolization with PHIL (precipitating hydrophobic injectable liquid). The calculated dose in the uterus was less than 1 µSv, which represents a negligible risk of harmful effects on the fetus. She delivered a baby at 37 weeks of gestation by cesarean section without complications. No congenital disorders were diagnosed by standard screening methods until the age of the newborn was two years. The angiography protocol must be optimized to minimize the radiation dose. Adequate shielding protection of the uterus is important. Premature termination of pregnancy is not necessary. Multidisciplinary care of neurologists, neurosurgeons, interventional radiologists, anesthesiologists, neonatologists, and obstetricians is necessary. Full article

(This article belongs to the Special Issue The Implications of General Conditions during Pregnancy on Possible Complications for Mother and Fetus)

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Open AccessReview

The Bacterial Nucleoid: From Electron Microscopy to Polymer Physics—A Personal Recollection

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Conrad L. Woldringh

Life 2023, 13(4), 895; https://doi.org/10.3390/life13040895 - 28 Mar 2023

Abstract

In the 1960s, electron microscopy did not provide a clear answer regarding the compact or dispersed organization of the bacterial nucleoid. This was due to the necessary preparation steps of fixation and dehydration (for embedding) and freezing (for freeze-fracturing). Nevertheless, it was possible [...] Read more.

In the 1960s, electron microscopy did not provide a clear answer regarding the compact or dispersed organization of the bacterial nucleoid. This was due to the necessary preparation steps of fixation and dehydration (for embedding) and freezing (for freeze-fracturing). Nevertheless, it was possible to measure the lengths of nucleoids in thin sections of slow-growing Escherichia coli cells, showing their gradual increase along with cell elongation. Later, through application of the so-called agar filtration method for electron microscopy, we were able to perform accurate measurements of cell size and shape. The introduction of confocal and fluorescence light microscopy enabled measurements of size and position of the bacterial nucleoid in living cells, inducing the concepts of “nucleoid occlusion” for localizing cell division and of “transertion” for the final step of nucleoid segregation. The question of why the DNA does not spread throughout the cytoplasm was approached by applying polymer-physical concepts of interactions between DNA and proteins. This gave a mechanistic insight in the depletion of proteins from the nucleoid, in accordance with its low refractive index observed by phase-contrast microscopy. Although in most bacterial species, the widely conserved proteins of the ParABS-system play a role in directing the segregation of newly replicated DNA strands, the basis for the separation and opposing movement of the chromosome arms was proposed to lie in preventing intermingling of nascent daughter strands already in the early replication bubble. E. coli, lacking the ParABS system, may be suitable for investigating this basic mechanism of DNA strand separation and segregation. Full article

(This article belongs to the Special Issue Novel Principles and Methods in Bacterial Cell Cycle Physiology: Celebrating the Charles E. Helmstetter Prize in 2022)

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Open AccessArticle

Crocus sativus Extract as a Biological Agent for Disease-Modifying Therapy of Collagenase-Induced Mouse Model of Osteoarthritis

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Life 2023, 13(4), 894; https://doi.org/10.3390/life13040894 - 28 Mar 2023

Abstract

Objectives: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to [...] Read more.

Objectives: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to be common to all forms of the disease. Currently used therapies for control of the disease are mainly nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid medications. The aim of this study was to investigate the extract from Crocus sativus as a biological disease-suppressing therapy agent. Methods: Balb/c mice were injected intra-articularly with Clostridium histolyticum type IA for induction of osteoarthritis. The mice were randomized to five groups: control group, I group (CIOA untreated), II group (CIOA + 100 mg/kg/daily saffron), III group (CIOA + 50 mg/kg/daily saffron), IV group (CIOA + 25 mg/kg/daily saffron). Flow-cytometry analysis was used to study the splenocytes’ phenotype isolated from the treated animals. The serum levels of inflammatory and anti-inflammatory cytokines were analyzed with ELISA. The histological assessment was used to analyze the saffron extract effect on histopathological alterations. Results: Saffron treatment significantly decreased osteoarthritis-associated joint histological manifestations and decreased serum TNFα levels. The flow-cytometry analysis showed a decrease in pro-inflammatory immune cell subtypes in the spleen. Conclusions: The results obtained suggest that saffron affected the disease progression and could be a potential therapeutic approach in osteoarthritic patients’ therapy. Full article

(This article belongs to the Special Issue Current Views on Knee Osteoarthritis-Volume II)

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Open AccessArticle

Bioactive Compounds and Signaling Pathways of Wolfiporia extensa in Suppressing Inflammatory Response by Network Pharmacology

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Juri Jin

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Md. Helal Uddin Chowdhury

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Md. Hafizur Rahman

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Ki-Young Choi

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Md. Adnan

Life 2023, 13(4), 893; https://doi.org/10.3390/life13040893 - 27 Mar 2023

Abstract

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through [...] Read more.

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through network pharmacology. Methanol (ME) extract of WE (MEWE) was used for GC-MS analysis to identify the bioactives, which were screened by following Lipinski’s rules. Public databases were used to extract selected bioactives and inflammation-related targets, and Venn diagrams exposed the common targets. Then, STRING and Cytoscape tools were used to construct protein-protein (PPI) network and mushroom-bioactives-target (M-C-T) networks. Gene Ontology and KEGG pathway analysis were performed by accessing the DAVID database and molecular docking was conducted to validate the findings. The chemical reactivity of key compounds and standard drugs was explored by the computational quantum mechanical modelling method (DFT study). Results from GC-MS revealed 27 bioactives, and all obeyed Lipinski’s rules. The public databases uncovered 284 compound-related targets and 7283 inflammation targets. A Venn diagram pointed to 42 common targets which were manifested in the PPI and M-C-T networks. KEGG analysis pointed to the HIF-1 signaling pathway and, hence, the suggested strategy for preventing the onset of inflammatory response was inhibition of downstream NFKB, MAPK, mTOR, and PI3K-Akt signaling cascades. Molecular docking revealed the strongest binding affinity for “N-(3-chlorophenyl) naphthyl carboxamide” on five target proteins associated with the HIF-1 signaling pathway. Compared to the standard drug utilized in the DFT (Density Functional Theory) analysis, the proposed bioactive showed a good electron donor component and a reduced chemical hardness energy. Our research pinpoints the therapeutic efficiency of MEWE and this work suggests a key bioactive compound and its action mechanism against inflammation. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science–Volume II)

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Open AccessReview

Endoscopic Submucosal Dissection for Esophageal Cancer: Current and Future

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Yuki Okubo

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Ryu Ishihara

Life 2023, 13(4), 892; https://doi.org/10.3390/life13040892 - 27 Mar 2023

Abstract

Endoscopic submucosal dissection (ESD) has been widely used to treat superficial esophageal cancer. The advantages of esophageal ESD include a high en bloc resection rate and accurate pathological diagnosis. It enables local resection of the primary tumor and accurate identification of the risk [...] Read more.

Endoscopic submucosal dissection (ESD) has been widely used to treat superficial esophageal cancer. The advantages of esophageal ESD include a high en bloc resection rate and accurate pathological diagnosis. It enables local resection of the primary tumor and accurate identification of the risk factors for lymph node metastasis, including depth, vascular invasion, and types of invasion. Even in cases with clinical T1b-SM cancer, ESD and additional treatment can achieve radical cure, depending on the risk of lymph node metastasis. Esophageal ESD will be increasingly vital in minimally invasive and effective esophageal cancer treatment. This article describes the current status and prospects of esophageal ESD. Full article

(This article belongs to the Special Issue Advances in Endoscopic Therapy for Gastrointestinal Disease)

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Open AccessArticle

Heart Valve Surgery in Antiphospholipid Syndrome Patients—Morbidity and Mortality

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Life 2023, 13(4), 891; https://doi.org/10.3390/life13040891 - 27 Mar 2023

Abstract

Objectives: To assess valve surgery outcomes in antiphospholipid syndrome (APS). Methods: A retrospective study assessing complications and mortality rate and possible factors associated with adverse outcomes of APS patients undergoing valve surgery in two tertiary medical centers. Results: Twenty-six APS patients (median age [...] Read more.

Objectives: To assess valve surgery outcomes in antiphospholipid syndrome (APS). Methods: A retrospective study assessing complications and mortality rate and possible factors associated with adverse outcomes of APS patients undergoing valve surgery in two tertiary medical centers. Results: Twenty-six APS patients (median age at surgery 47.5 years) who underwent valve surgery were detected, of whom 11 (42.3%) had secondary APS. The mitral valve was most commonly involved (n = 15, 57.7%). A valve replacement was performed in 24 operations (92.3%), 16 of which (66.7%) were mechanical valves. Fourteen (53.8%) patients sustained severe complications, and four of them died. The presence of mitral regurgitation (MR) was associated with severe complications and mortality (odds ratio (95% confidence interval) 12.5 (1.85–84.442), p = 0.008, for complications. All deceased patients had MR (p = 0.033). The presence of Libman-Sacks endocarditis (LSE) (7.333 (1.272–42.294), p = 0.045), low C3 (6.667 (1.047–42.431), p = 0.05) and higher perioperative prednisone doses (15 ± 21.89 vs. 1.36 ± 3.23 mg/day, p = 0.046) were also associated with complications. A lower glomerular filtration rate (GFR) was associated with mortality (30.75 ± 19.47 vs. 70.68 ± 34.44 mL/min, p = 0.038). Conclusions: Significant morbidity and mortality were observed among APS patients undergoing valve surgery. MR was associated with mortality and complications. LSE, low complement and higher doses of corticosteroids were associated with complications, while a low GFR was associated with mortality. Full article

(This article belongs to the Special Issue Diagnosis and Management of Systemic Autoimmune Diseases)

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Open AccessArticle

Outcomes in Patients Admitted for Upper Gastrointestinal Bleeding and COVID-19 Infection: A Study of Two Years of the Pandemic

by

Sergiu Marian Cazacu

,

Daniela Elena Burtea

,

Vlad Florin Iovănescu

,

Dan Nicolae Florescu

,

Sevastița Iordache

,

Adina Turcu-Stiolica

,

Victor Mihai Sacerdotianu

and

Bogdan Silviu Ungureanu

Life 2023, 13(4), 890; https://doi.org/10.3390/life13040890 - 27 Mar 2023

Abstract

Upper gastrointestinal bleeding (UGIB) represents a major emergency, and patient management requires endoscopic assessment to ensure appropriate treatment. The impact of COVID-19 on patient mortality in UGIB may be related to the combination of respiratory failure and severe bleeding and indirectly to delayed [...] Read more.

Upper gastrointestinal bleeding (UGIB) represents a major emergency, and patient management requires endoscopic assessment to ensure appropriate treatment. The impact of COVID-19 on patient mortality in UGIB may be related to the combination of respiratory failure and severe bleeding and indirectly to delayed admissions or a reduction in endoscopic procedures. Methods: We conducted a retrospective study involving patients admitted between March 2020 and December 2021 with UGIB and confirmed. Our objective was to compare these types of patients with those negative for SARS-CoV-2 infection, as well as with a pre-pandemic group of patients admitted between May 2018 and December 2019. Results: Thirty-nine patients (4.7%) with UGIB had an active COVID-19 infection. A higher mortality rate (58.97%) and a high risk of death (OR 9.04, p < 0.0001) were noted in the COVID-19 pandemic, mostly because of respiratory failure; endoscopy was not performed in half of the cases. Admissions for UGIB have decreased by 23.7% during the pandemic. Conclusions: COVID-19 infection in patients admitted for UGIB was associated with a higher mortality rate because of respiratory failure and possible delays in or contraindications of treatment. Full article

(This article belongs to the Special Issue Application of Endoscopic Imaging in Gastrointestinal Disease)

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Open AccessReview

Tocilizumab for Severe COVID-19 Infection and Multisystem Inflammatory Syndrome in Adults and Children

by

Amber N. Edinoff

,

Edward Sanders Alpaugh

,

,

,

,

,

,

and

Life 2023, 13(4), 889; https://doi.org/10.3390/life13040889 - 27 Mar 2023

Abstract

Coronavirus disease 2019 (COVID-19) rapidly emerged as a global pandemic, placing imminent stress and burden on healthcare resources and workers worldwide. Many patients who present with a severe COVID-19 infection are at high risk of developing severe acute respiratory distress syndrome (ARDS), leading [...] Read more.

Coronavirus disease 2019 (COVID-19) rapidly emerged as a global pandemic, placing imminent stress and burden on healthcare resources and workers worldwide. Many patients who present with a severe COVID-19 infection are at high risk of developing severe acute respiratory distress syndrome (ARDS), leading to a vast number of patients requiring mechanical ventilation and a high mortality rate. Similar to Middle East respiratory syndrome, COVID-19 demonstrates an initial viral replication phase that manifests as a variety of symptoms typically flu-like in nature, followed by a profound inflammatory response leading to rapid production of cytokines and uncontrolled inflammation. There have also been many cases of COVID-19 in pediatric patients presenting with elevated inflammatory markers and multisystem involvement labeled as a multisystem inflammatory syndrome (MIS-C) by the world health organization (WHO). The recent treatment of systemic inflammatory response to COVID-19 targets the secondary phase involving cytokine release syndrome. The detrimental effects of IL-6 can be profound and elevated levels are associated with a higher mortality rate and mechanical ventilation. Tocilizumab is an IL-6 inhibitor most widely investigated to target cytokine storm syndrome. Since June 2021, the FDA enacted an emergency use authorization for tocilizumab in the treatment of COVID-19. Several clinical trials have investigated tocilizumab combined with corticosteroids for treating severe ARDS associated with COVID-19. An increasing amount of evidence suggests that targeting the cytokine storm syndrome related to COVID-19 can lead to improved outcomes, especially in those patients requiring mechanical ventilation and with a critical illness. Additional studies are warranted to further look at the positive effects of tocilizumab in the COVID-19 population while additionally defining possible adverse effects. Full article

(This article belongs to the Special Issue Immunity in Viral or Bacterial Infections)

Open AccessArticle

Renal Impairment Impact and Survival Analysis in a Romanian Cohort of HIV-1(F1)-Infected Children and Adolescents

by

Raluca Isac

,

Rodica Costa

,

Mirela Frandes

,

Voichita Elena Lazureanu

,

Ramona Florina Stroescu

,

Ruxandra Maria Steflea

,

Iulia-Cristina Bagiu

,

Florin George Horhat

,

Gratiana Nicoleta Chicin

,

Avram Cecilia Roberta

,

Pacurari Alina Cornelia

,

Gabriela Doros

and

Mihai Gafencu

Life 2023, 13(4), 888; https://doi.org/10.3390/life13040888 - 27 Mar 2023

Abstract

Human immunodeficiency virus (HIV) is a lentivirus that is transmissible through blood and other body fluids. During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and untested blood transfusions. Romania [...] Read more.

Human immunodeficiency virus (HIV) is a lentivirus that is transmissible through blood and other body fluids. During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and untested blood transfusions. Romania was a special case in the global acquired immunodeficiency syndrome (AIDS) pandemic, displaying the largest population of HIV-infected children by parental transmission between 1987–1990. In total, 205 HIV-infected patients from the western part of Romania were analyzed in this retrospective study. Over 70% of them had experienced horizontal transmission from an unknown source, while vertical transmission was identified in only five cases. Most patients had a moderate to severe clinical manifestation of HIV infection, 77.56% had undergone antiretroviral (ARV) treatment, most of them (71.21%) had experienced no adverse reactions and many of those with HIV (90.73%) had an undetectable viral load. Renal impairment was detected in one third of patients (34.63%). Patients born before 1990, male patients, patients diagnosed with HIV before the age of 10, and those undernourished or with renal impairment had a shorter average survival time than the group born after 1990, female patients, patients receiving ARV treatment, patients with a normal body mass index (BMI) and those without renal impairment. Periodical monitoring of the estimated glomerular filtration rate (eGFR) level, as well as the detection of protein excretion, should be taken into consideration worldwide when monitoring HIV-positive patients; this in order to detect even asymptomatic chronic kidney disease (CKD), and to manage these patients and prolong their lives. Full article

(This article belongs to the Special Issue Prevention, Assessment and Management of Infectious Diseases)

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