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Biomedicines, Volume 10, Issue 4 (April 2022) – 198 articles

Cover Story (view full-size image): Our research indicates a defect in proinsulin (PI) chaperone GRP94 leads to an accumulation of mishandled proinsulin in β-cells. This results in ER stress, inflammatory pathway activation, int-proteasome assembly, and GRP94-PI complex secretion. Simultaneously, increased MHC-I expression on β-cells enhances their visibility to immune cells. The secreted GRP94-PI complexes are taken up by antigen-presenting cells and cross-presented to CD8+ T-cells to trigger an immune attack against β-cells. View this paper
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16 pages, 6343 KiB  
Article
Generation of a Pure Culture of Neuron-like Cells with a Glutamatergic Phenotype from Mouse Astrocytes
by Gary Stanley Fernandes, Rishabh Deo Singh and Kyeong Kyu Kim
Biomedicines 2022, 10(4), 928; https://doi.org/10.3390/biomedicines10040928 - 18 Apr 2022
Cited by 5 | Viewed by 2634
Abstract
Astrocyte-to-neuron reprogramming is a promising therapeutic approach for treatment of neurodegenerative diseases. The use of small molecules as an alternative to the virus-mediated ectopic expression of lineage-specific transcription factors negates the tumorigenic risk associated with viral genetic manipulation and uncontrolled differentiation of stem [...] Read more.
Astrocyte-to-neuron reprogramming is a promising therapeutic approach for treatment of neurodegenerative diseases. The use of small molecules as an alternative to the virus-mediated ectopic expression of lineage-specific transcription factors negates the tumorigenic risk associated with viral genetic manipulation and uncontrolled differentiation of stem cells. However, because previously developed methods for small-molecule reprogramming of astrocytes to neurons are multistep, complex, and lengthy, their applications in biomedicine, including clinical treatment, are limited. Therefore, our objective in this study was to develop a novel chemical-based approach to the cellular reprogramming of astrocytes into neurons with high efficiency and low complexity. To accomplish that, we used C8-D1a, a mouse astrocyte cell line, to assess the role of small molecules in reprogramming protocols that otherwise suffer from inconsistencies caused by variations in donor of the primary cell. We developed a new protocol by which a chemical mixture formulated with Y26732, DAPT, RepSox, CHIR99021, ruxolitinib, and SAG rapidly and efficiently induced the neural reprogramming of astrocytes in four days, with a conversion efficiency of 82 ± 6%. Upon exposure to the maturation medium, those reprogrammed cells acquired a glutaminergic phenotype over the next eleven days. We also demonstrated the neuronal functionality of the induced cells by confirming KCL-induced calcium flux. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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16 pages, 3430 KiB  
Article
Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM)
by Myriam Holl, Marie-Lena Rasch, Lucas Becker, Anna-Lena Keller, Laura Schultze-Rhonhof, Felix Ruoff, Markus Templin, Silke Keller, Felix Neis, Franziska Keßler, Jürgen Andress, Cornelia Bachmann, Bernhard Krämer, Katja Schenke-Layland, Sara Y. Brucker, Julia Marzi and Martin Weiss
Biomedicines 2022, 10(4), 927; https://doi.org/10.3390/biomedicines10040927 - 18 Apr 2022
Cited by 8 | Viewed by 2291
Abstract
Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as [...] Read more.
Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders. Full article
(This article belongs to the Section Cell Biology and Pathology)
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19 pages, 1247 KiB  
Review
The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy
by Yu-Hsuan Hung, Li-Tzong Chen and Wen-Chun Hung
Biomedicines 2022, 10(4), 926; https://doi.org/10.3390/biomedicines10040926 - 18 Apr 2022
Cited by 1 | Viewed by 2371
Abstract
The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the “Trinity” in promoting tumorigenesis. Although unidirectional [...] Read more.
The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the “Trinity” in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the “Trinity” members in the tumor microenvironment and propose a functional network for how these members communicate with each other. In addition, we discuss the underlying mechanisms mediating the interplay. Moreover, correlations of the alterations in the distribution and functionality of cancer cells, fibroblasts, and immune cells under different circumstances are reviewed. Finally, we point out the future application of CD8+ T cell-oriented therapy in the treatment of pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer: From Mechanisms to Therapeutic Approaches)
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18 pages, 1822 KiB  
Article
Tandem Repeat Diversity in Two Closely Related Hamster Species—The Chinese Hamster (Cricetulus griseus) and Striped Hamster (Cricetulus barabensis)
by Nadezhda G. Ivanova, Irina V. Kartavtseva, Vera N. Stefanova, Dmitrii I. Ostromyshenskii and Olga I. Podgornaya
Biomedicines 2022, 10(4), 925; https://doi.org/10.3390/biomedicines10040925 - 18 Apr 2022
Cited by 3 | Viewed by 2244
Abstract
The Chinese hamster (Cricetulus griseus) and striped hamster (Cricetulus barabensis) are very closely related species with similar karyotypes. The karyotypes differ from each other by one Robertsonian rearrangement and X-chromosome morphology. The level of the tandem repeat (TR) sequences’ [...] Read more.
The Chinese hamster (Cricetulus griseus) and striped hamster (Cricetulus barabensis) are very closely related species with similar karyotypes. The karyotypes differ from each other by one Robertsonian rearrangement and X-chromosome morphology. The level of the tandem repeat (TR) sequences’ evolutional variability is high. The aim of the current work was to trace the TR distribution on the chromosomes of two very closely related species. The striped hamster genome has not yet been sequenced. We classified the Chinese hamster TR in the assemblies available and then compared the mode of the TR distribution in closely related species. Chinese and striped hamsters are separate species due to the relative species specificity of Chinese hamster TR and prominent differences in the TR distribution in both species. The TR variation observed within homologous striped hamster chromosomes is caused by a lack of inbreeding in natural populations. The set of TR tested could be used to examine the CHO lines’ instability that has been observed in heterochromatic regions. Full article
(This article belongs to the Special Issue Advances in Molecular Cytogenetics)
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16 pages, 4641 KiB  
Article
Extremely Low-Frequency Electromagnetic Fields Increase Cytokines in Human Hair Follicles through Wnt/β-Catenin Signaling
by Ju-Hye Choi, Yu-Mi Kim, Hee-Jung Park, Myeong-Hyun Nam and Young-Kwon Seo
Biomedicines 2022, 10(4), 924; https://doi.org/10.3390/biomedicines10040924 - 18 Apr 2022
Cited by 1 | Viewed by 3286
Abstract
Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair loss must be developed, and electromagnetic field (EMF) therapy has been proven to be a promising medical [...] Read more.
Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair loss must be developed, and electromagnetic field (EMF) therapy has been proven to be a promising medical treatment in various fields, including hair loss treatment. This study evaluated the effect of extremely low-frequency electromagnetic field (ELF-EMF) intensity and exposure time by analyzing the expression of cytokines and anagen-related molecules, which influence hair activation and growth, in hair bulb spheroid (HBS) and hair follicle (HF) organ cultures. ELF-EMFs did not induce toxicity in the HBSs, as verified via the lactate dehydrogenase (LDH) assay. Moreover, an ELF-EMF intensity of 5–20 G promoted the expression of ALP, versican, β-catenin, and several cytokines (VEGF, PDGF, FGF-10, and ET-1) in HBSs. Immunohistochemical staining showed that ELF-EMF at an intensity of 5–20 G upregulated ALP and β-catenin and decreased TUNEL staining in HBS. Moreover, HFs exposed to ELF-EMF for 60 min exhibited an increase in hair length and a 1.5-fold increase in IL-4, ICAM-1, ALP, and versican mRNA expression compared to the control. Immunohistochemical staining indicated that 60 min of ELF-EMF can increase the expression of ALP and β-catenin and decreases TUNEL staining in organ cultures. Collectively, our results demonstrated that ELF-EMF exposure at a 10 G intensity for 60 min promoted hair shaft growth in HFs due to the effect of cytokines and adhesion molecules via the Wnt/β-catenin pathway. Therefore, ELF-EMF is a promising treatment for hair loss. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Physical Stimulation)
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12 pages, 1428 KiB  
Article
Effects of Reversal of Hypotension on Cerebral Microcirculation and Metabolism in Experimental Sepsis
by Fabio Silvio Taccone, Fuhong Su, Xinrong He, Lorenzo Peluso, Katia Donadello, Sabino Scolletta, Daniel De Backer and Jean-Louis Vincent
Biomedicines 2022, 10(4), 923; https://doi.org/10.3390/biomedicines10040923 - 18 Apr 2022
Cited by 1 | Viewed by 1631
Abstract
The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < [...] Read more.
The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < 65 mmHg, unresponsive to fluid challenge), a norepinephrine infusion was titrated in eight sheep to restore a MAP ≥ 75 mmHg; the other four sheep were kept hypotensive. The microcirculation of the cerebral cortex was evaluated using side-stream dark-field video-microscopy. Brain partial pressure of oxygen (PbtO2) was measured, and cerebral metabolism was assessed using microdialysis. All animals developed septic shock after a median of 15 (14–19) h. When MAP was raised using norepinephrine, the PbtO2 increased significantly (from 41 ± 4 to 55 ± 5 mmHg), and the cerebral lactate/pyruvate ratio decreased (from 47 ± 13 to 28 ± 4) compared with values at shock onset. Changes in the microcirculation were unchanged with restoration of MAP and the glutamate increased further (from 17 ± 11 to 23 ± 16 μM), as it did in the untreated animals. In septic shock, the correction of hypotension with vasopressors may improve cerebral oxygenation but does not reverse the alterations in brain microcirculation or cerebral metabolism. Full article
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3 pages, 199 KiB  
Editorial
Molecular Mechanisms in Lysosomal Storage Diseases: From Pathogenesis to Therapeutic Strategies
by Valeria De Pasquale, Melania Scarcella and Luigi Michele Pavone
Biomedicines 2022, 10(4), 922; https://doi.org/10.3390/biomedicines10040922 - 17 Apr 2022
Cited by 2 | Viewed by 1499
Abstract
Lysosomal storage diseases (LSDs) are a group of metabolic diseases caused by inborn mutations of lysosomal enzymes, which lead to lysosome substrate accumulation in various cell types [...] Full article
15 pages, 666 KiB  
Review
Oncology Drug Repurposing for Sepsis Treatment
by Izabela Rumienczyk, Maria Kulecka, Małgorzata Statkiewicz, Jerzy Ostrowski and Michal Mikula
Biomedicines 2022, 10(4), 921; https://doi.org/10.3390/biomedicines10040921 - 17 Apr 2022
Cited by 5 | Viewed by 2201
Abstract
Sepsis involves life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite three decades of efforts and multiple clinical trials, no treatment, except antibiotics and supportive care, has been approved for this devastating syndrome. Simultaneously, numerous preclinical studies have shown the [...] Read more.
Sepsis involves life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite three decades of efforts and multiple clinical trials, no treatment, except antibiotics and supportive care, has been approved for this devastating syndrome. Simultaneously, numerous preclinical studies have shown the effectiveness of oncology-indicated drugs in ameliorating sepsis. Here we focus on cataloging these efforts with both oncology-approved and under-development drugs that have been repositioned to treat bacterial-induced sepsis models. In this context, we also envision the exciting prospect for further standard and oncology drug combination testing that could ultimately improve clinical outcomes in sepsis. Full article
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14 pages, 727 KiB  
Review
The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer
by Klaudia Parafiniuk, Wiktoria Skiba, Anna Pawłowska, Dorota Suszczyk, Aleksandra Maciejczyk and Iwona Wertel
Biomedicines 2022, 10(4), 920; https://doi.org/10.3390/biomedicines10040920 - 16 Apr 2022
Cited by 8 | Viewed by 2615
Abstract
Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to [...] Read more.
Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to the development of the adipokine hypothesis. Omental adipocyte cells interact with cancer cells, promoting their migration and metastasis via the secretion of adipokines, growth factors, and hormones. One of the adipokines is resistin. It was shown in vitro that resistin stimulates the growth and differentiation of ovarian cancer cells. Moreover, it increases the level of angiogenesis factors, e.g., matrix metalloproteinase 2 (MMP-2) and vascular epithelial growth factor (VEGF). Additionally, resistin induces epithelial–mesenchymal transition (EMT) and stemness in EOC cell lines. A positive correlation has been shown between a higher level of resistin expression and the stage of histological differentiation of EOC or the occurrence of lymph node metastases. In addition, the overexpression of resistin has been found to act as an independent factor determining disease-free survival as well as overall survival in EOC patients. Growing evidence supports the finding that resistin plays an important role in some mechanisms leading to the progression of EOC, though this issue still requires further research. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines in Cancer Progression)
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13 pages, 3335 KiB  
Article
miR-195-5p Regulates Tight Junctions Expression via Claudin-2 Downregulation in Ulcerative Colitis
by Viviana Scalavino, Emanuele Piccinno, Antonio Lacalamita, Angela Tafaro, Raffaele Armentano, Gianluigi Giannelli and Grazia Serino
Biomedicines 2022, 10(4), 919; https://doi.org/10.3390/biomedicines10040919 - 16 Apr 2022
Cited by 9 | Viewed by 2313
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of intestinal permeability and barrier function. We identified 18 dysregulated miRNAs in intestinal epithelial cells (IECs) from the ulcerative colitis (UC) mice model and control mice. Among them, down-regulated miR-195-5p targeted claudin-2 (CLDN2) and was involved in impaired barrier function. CLDN2 expression levels were increased in UC mice models and negatively correlated with miR-195-5p expression. We demonstrated that gain-of-function of miR-195-5p in colonic epithelial cell lines decreased the CLDN2 levels. This modulation, in turn, downregulated claudin-1 (CLDN1) expression at protein level but not that of occludin. Our data support a previously unreported role of miR-195-5p in intestinal tight junctions’ regulation and suggest a potential pharmacological target for new therapeutic approaches in IBD. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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13 pages, 1786 KiB  
Article
Expression of the Costimulatory Molecule B7-H4 in the Decidua and Placental Tissues in Patients with Placental Abruption
by Monika Bączkowska, Magdalena Maria Dutsch-Wicherek, Ewa Przytuła, Jan Faryna, Cezary Wojtyła, Mohamed Ali, Anna Knafel and Michał Ciebiera
Biomedicines 2022, 10(4), 918; https://doi.org/10.3390/biomedicines10040918 - 16 Apr 2022
Cited by 1 | Viewed by 1929
Abstract
B7 homolog 4 protein (B7-H4), a member of the B7 family, is a immunomodulatory membrane protein. The aim of the study was to evaluate the expression of this protein in the decidua and placental tissues in case of placental abruption (PA) compared to [...] Read more.
B7 homolog 4 protein (B7-H4), a member of the B7 family, is a immunomodulatory membrane protein. The aim of the study was to evaluate the expression of this protein in the decidua and placental tissues in case of placental abruption (PA) compared to cases of retained placental tissue (RPT) and controls. Tissue samples were obtained from 47 patients with PA, 60 patients with RPT, and 41 healthy controls. The samples were stained for B7-H4 expression, analyzed by an expert pathologist, and a semi-quantitative scale was applied. A statistical analysis revealed that the expression of B7-H4 was significantly higher in the decidua in PA samples compared to samples from patients with RPT (p-value < 0.001) and healthy controls (p-value < 0.001). The expression of B7-H4 in the placental chorionic villus was significantly higher in PA samples in relation to samples from healthy controls (p-value < 0.001) but not in relation to RPT samples (p-value = 0.0853). This finding suggests that B7-H4 might play an important role in mechanisms restoring reproductive tract homeostasis. Further research is necessary in regard to the role of B7-H4 in PA. Full article
(This article belongs to the Topic Pathogenesis of Pregnancy-Related Complications)
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19 pages, 4731 KiB  
Article
Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
by Yitang Yan, Min Shi, Rick Fannin, Linda Yu, Jingli Liu, Lysandra Castro and Darlene Dixon
Biomedicines 2022, 10(4), 917; https://doi.org/10.3390/biomedicines10040917 - 16 Apr 2022
Cited by 1 | Viewed by 2037
Abstract
Cadmium (Cd) is one of the most prevalent environmental heavy metal contaminants and is considered an endocrine disruptor and carcinogen. In women with uterine fibroids, there is a correlation between blood Cd levels and fibroid tumor size. In this study, fibroid cells were [...] Read more.
Cadmium (Cd) is one of the most prevalent environmental heavy metal contaminants and is considered an endocrine disruptor and carcinogen. In women with uterine fibroids, there is a correlation between blood Cd levels and fibroid tumor size. In this study, fibroid cells were exposed to 10 µM CdCl2 for 6 months and a fast-growing Cd-Resistant Leiomyoma culture, termed CR-LM6, was recovered. To characterize the morphological and mechanodynamic features of uterine fibroid cells associated with prolonged Cd exposure, we conducted time lapse imaging using a Zeiss confocal microscope and analyzed data by Imaris and RStudio. Our experiments recorded more than 64,000 trackable nuclear surface objects, with each having multiple parameters such as nuclear size and shape, speed, location, orientation, track length, and track straightness. Quantitative analysis revealed that prolonged Cd exposure significantly altered cell migration behavior, such as increased track length and reduced track straightness. Cd exposure also significantly increased the heterogeneity in nuclear size. Additionally, Cd significantly increased the median and variance of instantaneous speed, indicating that Cd exposure results in higher speed and greater variation in motility. Profiling of mRNA by NanoString analysis and Ingenuity Pathway Analysis (IPA) strongly suggested that the direction of gene expression changes due to Cd exposure enhanced cell movement and invasion. The altered expression of extracellular matrix (ECM) genes such as collagens, matrix metallopeptidases (MMPs), secreted phosphoprotein 1 (SPP1), which are important for migration contact guidance, may be responsible for the greater heterogeneity. The significantly increased heterogeneity of nuclear size, speed, and altered migration patterns may be a prerequisite for fibroid cells to attain characteristics favorable for cancer progression, invasion, and metastasis. Full article
(This article belongs to the Special Issue Advanced Research in Cell Motility)
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12 pages, 1791 KiB  
Article
Post-Bariatric Hypoglycemia Is Associated with Endothelial Dysfunction and Increased Oxidative Stress
by Roberta Lupoli, Ilenia Calcaterra, Giuseppe Annunziata, Giancarlo Tenore, Carmen Rainone, Luigi Schiavo, Brunella Capaldo and Matteo Nicola Dario Di Minno
Biomedicines 2022, 10(4), 916; https://doi.org/10.3390/biomedicines10040916 - 16 Apr 2022
Cited by 4 | Viewed by 2296
Abstract
Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH [...] Read more.
Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (β = −0.781, p < 0.001), D-ROMs (β = 0.548, p = 0.023) and oxLDL levels (β = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress. Full article
(This article belongs to the Special Issue Biomedicines: 10th Anniversary)
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27 pages, 2980 KiB  
Review
Elucidating miRNA Function in Cancer Biology via the Molecular Genetics’ Toolbox
by Adam Azlan, Yaashini Rajasegaran, Khor Kang Zi, Aliaa Arina Rosli, Mot Yee Yik, Narazah Mohd Yusoff, Olaf Heidenreich and Emmanuel Jairaj Moses
Biomedicines 2022, 10(4), 915; https://doi.org/10.3390/biomedicines10040915 - 15 Apr 2022
Cited by 4 | Viewed by 2350
Abstract
Micro-RNA (miRNAs) are short non-coding RNAs of about 18–20 nucleotides in length and are implicated in many cellular processes including proliferation, development, differentiation, apoptosis and cell signaling. Furthermore, it is well known that miRNA expression is frequently dysregulated in many cancers. Therefore, this [...] Read more.
Micro-RNA (miRNAs) are short non-coding RNAs of about 18–20 nucleotides in length and are implicated in many cellular processes including proliferation, development, differentiation, apoptosis and cell signaling. Furthermore, it is well known that miRNA expression is frequently dysregulated in many cancers. Therefore, this review will highlight the various mechanisms by which microRNAs are dysregulated in cancer. Further highlights include the abundance of molecular genetics tools that are currently available to study miRNA function as well as their advantages and disadvantages with a special focus on various CRISPR/Cas systems This review provides general workflows and some practical considerations when studying miRNA function thus enabling researchers to make informed decisions in regards to the appropriate molecular genetics tool to be utilized for their experiments. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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21 pages, 3533 KiB  
Article
Phosphatidylethanolamine Deficiency and Triglyceride Overload in Perilesional Cortex Contribute to Non-Goal-Directed Hyperactivity after Traumatic Brain Injury in Mice
by Lisa Hahnefeld, Alexandra Vogel, Robert Gurke, Gerd Geisslinger, Michael K. E. Schäfer and Irmgard Tegeder
Biomedicines 2022, 10(4), 914; https://doi.org/10.3390/biomedicines10040914 - 15 Apr 2022
Cited by 6 | Viewed by 1889
Abstract
Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including headache, fatigue, insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of endocannabinoids [...] Read more.
Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including headache, fatigue, insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of endocannabinoids in the perilesional cortex. We now analyzed lipidome patterns in the brain and plasma in TBI versus sham mice in association with key behavioral parameters and endocannabinoids. Lipidome profiles in the plasma and subcortical ipsilateral and contralateral brain were astonishingly equal in sham and TBI mice, but the ipsilateral perilesional cortex revealed a strong increase in neutral lipids represented by 30 species of triacylglycerols (TGs) of different chain lengths and saturation. The accumulation of TG was localized predominantly to perilesional border cells as revealed by Oil Red O staining. In addition, hexosylceramides (HexCer) and phosphatidylethanolamines (PE and ether-linked PE-O) were reduced. They are precursors of gangliosides and endocannabinoids, respectively. High TG, low HexCer, and low PE/PE-O showed a linear association with non-goal-directed nighttime hyperactivity but not with the loss of avoidance memory. The analyses suggest that TG overload and HexCer and PE deficiencies contributed to behavioral dimensions of post-TBI psychopathology. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Brain Injury)
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15 pages, 2061 KiB  
Review
Inorganic Polyphosphate—Regulator of Cellular Metabolism in Homeostasis and Disease
by Filip Kus, Ryszard T. Smolenski and Marta Tomczyk
Biomedicines 2022, 10(4), 913; https://doi.org/10.3390/biomedicines10040913 - 15 Apr 2022
Cited by 6 | Viewed by 2775
Abstract
Inorganic polyphosphate (polyP), a simple anionic polymer consisting of even hundreds of orthophosphate units, is a universal molecule present in both simple and complex organisms. PolyP controls homeostatic processes in animals, such as blood coagulation, tissue regeneration, and energy metabolism. Furthermore, this polymer [...] Read more.
Inorganic polyphosphate (polyP), a simple anionic polymer consisting of even hundreds of orthophosphate units, is a universal molecule present in both simple and complex organisms. PolyP controls homeostatic processes in animals, such as blood coagulation, tissue regeneration, and energy metabolism. Furthermore, this polymer is a potent regulator of inflammation and influences host immune response in bacterial and viral infections. Disturbed polyP systems have been related to several pathological conditions, including neurodegeneration, cardiovascular disorders, and cancer, but we lack a full understanding of polyP biogenesis and mechanistic insights into the pathways through which polyP may act. This review summarizes recent studies that describe the role of polyP in cell homeostasis and show how disturbances in polyP levels may lead to disease. Based on the collected findings, we highlight the possible usage of this polymer as a promising therapeutic tool in multiple pathologies. Full article
(This article belongs to the Special Issue Inorganic Phosphate Homeostasis and Signaling in Eukaryotic Cells)
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28 pages, 3641 KiB  
Article
Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms’ Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49)
by Dorin Novacescu, Talida Georgiana Cut, Alin Adrian Cumpanas, Silviu Constantin Latcu, Razvan Bardan, Ovidiu Ferician, Cosmin-Ciprian Secasan, Andrei Rusmir and Marius Raica
Biomedicines 2022, 10(4), 912; https://doi.org/10.3390/biomedicines10040912 - 15 Apr 2022
Cited by 5 | Viewed by 2634
Abstract
Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive [...] Read more.
Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes. Full article
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15 pages, 1047 KiB  
Article
The Immunogenicity and Safety of Three Types of SARS-CoV-2 Vaccines in Adult Patients with Immune-Mediated Inflammatory Diseases: A Longitudinal Cohort Study
by Ni Tien, Yu-Chang Chang, Po-Ku Chen, Hui-Ju Lin, Shih-Hsin Chang, Joung-Liang Lan, Po-Ren Hsueh, Ching-Kun Chang and Der-Yuan Chen
Biomedicines 2022, 10(4), 911; https://doi.org/10.3390/biomedicines10040911 - 15 Apr 2022
Cited by 8 | Viewed by 5740
Abstract
Patients with immune-mediated inflammatory diseases (IMID) were seldom enrolled in the studies of SARS-CoV-2 vaccines, and real-world data regarding the immunogenicity of different types of vaccines is limited. We aimed to assess the immunogenicity and safety of three types of vaccines (AZD1222, mRNA-1273, [...] Read more.
Patients with immune-mediated inflammatory diseases (IMID) were seldom enrolled in the studies of SARS-CoV-2 vaccines, and real-world data regarding the immunogenicity of different types of vaccines is limited. We aimed to assess the immunogenicity and safety of three types of vaccines (AZD1222, mRNA-1273, and BNT162b2) in 253 patients with IMID and 30 healthcare workers (HCWs). Plasma levels of IgG-antibody against SARS-CoV-2 targeting the receptor-binding domain of spike protein (anti-S/RBD-IgG) were determined by chemiluminescent immunoassay 3–4 weeks after the first-dose and second-dose vaccination. The positive rate and titers of anti-S/RBD-IgG were significantly higher in mRNA-1273 or BNT162b2 than in the AZD1222 vaccine. Immunogenicity was augmented after the second dose of any vaccine type in all IMID patients, suggesting that these patients should complete the vaccination series. Anti-S/RBD-IgG titers after first-dose vaccination were significantly lower in RA patients than pSS patients, but there was no significant difference after second-dose vaccination among five groups of IMID patients. The positive rate and titers of anti-S/RBD-IgG were significantly lower in patients receiving abatacept/rituximab therapy than in those receiving other DMARDs. All three SARS-CoV-2 vaccines showed acceptable safety profiles, and the common AEs were injection site reactions. We identified SLE as a significant predictor of increased autoimmunity and would like to promote awareness of the possibility of autoimmunity following vaccination. Full article
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11 pages, 1204 KiB  
Article
Expression and Prognostic Implication of PD-L1 in Patients with Urothelial Carcinoma with Variant Histology (Squamous Differentiation or Micropapillary) Undergoing Radical Cystectomy
by Jae-Hoon Chung, Chung-Un Lee, Dong-Hyeon Lee and Wan Song
Biomedicines 2022, 10(4), 910; https://doi.org/10.3390/biomedicines10040910 - 15 Apr 2022
Cited by 2 | Viewed by 1660
Abstract
The expression and prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TICs) has not been determined in urothelial carcinoma (UC) with variant histology. We retrospectively reviewed 90 patients (44 with micropapillary variant of UC (MPUC) and 46 with UC with [...] Read more.
The expression and prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TICs) has not been determined in urothelial carcinoma (UC) with variant histology. We retrospectively reviewed 90 patients (44 with micropapillary variant of UC (MPUC) and 46 with UC with squamous differentiation (UCSD)) who underwent radical cystectomy between January 2013 and December 2019. The expression of PD-L1 in TICs was measured using the VENTANA (SP-142) immunohistochemistry assay and dichotomized using a 5% cutoff value (positive ≥ 5%). Kaplan–Meier survival analysis was used to estimate recurrence-free survival (RFS), and multivariable Cox proportional hazard models were used to identify factors predicting tumor recurrence. Overall, positive PD-L1 expression in TICs was confirmed in 50 of 90 (55.6%) patients (40.1% (18/44) of MPUC and 69.9% (32/46) of UCSD). RFS was significantly shorter in patients with positive PD-L1 expression in TICs than in those with negative PD-L1 expression both in MPUC (p = 0.005) and UCSD (p = 0.046). Positive PD-L1 expression in TICs was significantly associated with an increased risk of tumor recurrence in both MPUC (HR = 1.85; 95% CI: 1.323–2.672; p = 0.017) and UCSD (HR = 1.58; 95% CI: 1.162–2.780; p = 0.032). In conclusion, positive PD-L1 expression in TICs was significantly associated with poorer RFS in both MPUC and UCSD patients. Our results support the use of adjuvant immunotherapy in these patients if they test positive for PD-L1 in their TICs. Full article
(This article belongs to the Topic Cancer Biology and Therapy)
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17 pages, 3277 KiB  
Article
Testicular “Inherited Metabolic Memory” of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content
by Luís Crisóstomo, Matthieu Bourgery, Luís Rato, João F. Raposo, Rachel L. Batterham, Noora Kotaja and Marco G. Alves
Biomedicines 2022, 10(4), 909; https://doi.org/10.3390/biomedicines10040909 - 15 Apr 2022
Cited by 9 | Viewed by 2500
Abstract
Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular “inherited metabolic memory” [...] Read more.
Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular “inherited metabolic memory” of ancestral HFD, using a transgenerational rodent model. Male founders were fed a standard chow for 200 days (CTRL), HFD for 200 days (HFD), or standard chow for 60 days followed by HFD for 140 days (HFDt). The male offspring and grand-offspring were fed standard chow for 200 days. The sncRNA sequencing from epidydimal spermatozoa revealed signatures associated with testicular metabolic plasticity in HFD-exposed mice and in the unexposed progeny. Sperm tRNA-derived RNA (tsRNA) and repeat-derived small RNA (repRNA) content were specially affected by HFDt and in the offspring of HFD and HFDt mice. The grand-offspring of HFD and HFDt mice showed lower sperm counts than CTRL descendants, whereas the sperm miRNA content was affected. Although the causality between sperm sncRNAs content and transgenerational epigenetic inheritance of HFD-related traits remains elusive, our results suggest that sperm sncRNA content is influenced by ancestral exposure to HFD, contributing to the sperm epigenome up to the grand-offspring. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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18 pages, 41562 KiB  
Article
Recognition of Tumor Nidogen-1 by Neutrophil C-Type Lectin Receptors
by Ronit Vogt Sionov, Chrystelle Lamagna and Zvi Granot
Biomedicines 2022, 10(4), 908; https://doi.org/10.3390/biomedicines10040908 - 15 Apr 2022
Cited by 2 | Viewed by 2150
Abstract
Neutrophil-mediated cytotoxicity toward tumor cells requires cell contact and is mediated by hydrogen peroxide. We have recently shown that Cathepsin G expressed on the neutrophil surface interacts with tumor RAGE, and this interaction facilitates neutrophil cytotoxicity. Interruption of the Cathepsin G–RAGE interaction led [...] Read more.
Neutrophil-mediated cytotoxicity toward tumor cells requires cell contact and is mediated by hydrogen peroxide. We have recently shown that Cathepsin G expressed on the neutrophil surface interacts with tumor RAGE, and this interaction facilitates neutrophil cytotoxicity. Interruption of the Cathepsin G–RAGE interaction led to 50–80% reduction in cytotoxicity, suggesting that additional interactions are also involved. Here we show that blocking antibodies to the C-type lectin receptors (CLRs) Clec4e and Dectin-1, but not those to NKG2D, attenuated murine neutrophil cytotoxicity towards murine tumor cells, suggesting a contributing role for these CLRs in neutrophil recognition of tumor cells. We further observed that the CLRs interact with tumor Nidogen-1 and Hspg2, two sulfated glycoproteins of the basement membrane. Both Nidogen-1 and Hspg2 were found to be expressed on the tumor cell surface. The knockdown of Nidogen-1, but not that of Hspg2, led to reduced susceptibility of the tumor cells to neutrophil cytotoxicity. Altogether, this study suggests a role for CLR–Nidogen-1 interaction in the recognition of tumor cells by neutrophils, and this interaction facilitates neutrophil-mediated killing of the tumor cells. Full article
(This article belongs to the Collection Advances in Leukocyte Biology)
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22 pages, 3821 KiB  
Article
Potent and Broad-Spectrum Bactericidal Activity of a Nanotechnologically Manipulated Novel Pyrazole
by Silvana Alfei, Debora Caviglia, Alessia Zorzoli, Danilo Marimpietri, Andrea Spallarossa, Matteo Lusardi, Guendalina Zuccari and Anna Maria Schito
Biomedicines 2022, 10(4), 907; https://doi.org/10.3390/biomedicines10040907 - 15 Apr 2022
Cited by 5 | Viewed by 1701
Abstract
The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered [...] Read more.
The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered to this end. To overcome the CR232 water solubility issue and allow for the determination of reliable minimum inhibitory concentration values (MICs), we initially prepared water-soluble and clinically applicable CR232-loaded nanoparticles (CR232-G5K NPs), as previously reported. Here, CR232-G5K NPs have been tested on several clinically isolates of Gram-positive and Gram-negative species, including MDR strains. While for CR232 MICs ≥ 128 µg/mL (376.8 µM) were obtained, very low MICs (0.36–2.89 µM) were observed for CR232-G5K NPs against all of the considered isolates, including colistin-resistant isolates of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemases (KPCs)-producing K. pneumoniae (0.72 µM). Additionally, in time–kill experiments, CR232-G5K NPs displayed a rapid bactericidal activity with no significant regrowth after 24 h on all isolates tested, regardless of their difficult-to-treat resistance. Conjecturing a clinical use of CR232-G5K NPs, cytotoxicity experiments on human keratinocytes were performed, determining very favorable selectivity indices. Collectively, due to its physicochemical and biological properties, CR232-G5K NPs could represent a new potent weapon to treat infections sustained by broad spectrum MDR bacteria. Full article
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17 pages, 3567 KiB  
Article
Investigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells
by Huong Thu Vu, Mi-Ran Han, Jun-Haeng Lee, Jong-Soo Kim, Ji-Sun Shin, Ji-Young Yoon, Jeong-Hui Park, Khandmaa Dashnyam, Jonathan Campbell Knowles, Hae-Hyoung Lee, Jong-Bin Kim and Jung-Hwan Lee
Biomedicines 2022, 10(4), 906; https://doi.org/10.3390/biomedicines10040906 - 15 Apr 2022
Cited by 6 | Viewed by 2779
Abstract
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have [...] Read more.
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration. Full article
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26 pages, 4257 KiB  
Review
Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases
by Muhammad Tahir, Sakhawat Ali, Wenting Zhang, Boqiang Lv, Wenge Qiu and Juan Wang
Biomedicines 2022, 10(4), 905; https://doi.org/10.3390/biomedicines10040905 - 15 Apr 2022
Cited by 5 | Viewed by 2252
Abstract
Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely [...] Read more.
Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely investigated for its therapeutic activities. Aloperine is proven to be an effective therapeutic agent against many human pathological conditions, including cancer, viral diseases, and cardiovascular and inflammatory disorders. Aloperine is reported to exert therapeutic effects through triggering various biological processes, including cell cycle arrest, apoptosis, autophagy, suppressing cell migration, and invasion. It has also been found to be associated with the modulation of various signaling pathways in different diseases. In this review, we summarize the most recent knowledge on the modulatory effects of aloperine on various critical biological processes and signaling mechanisms, including the PI3K, Akt, NF-κB, Ras, and Nrf2 pathways. These data demonstrate that aloperine is a promising therapeutic candidate. Being a potent modulator of signaling mechanisms, aloperine can be employed in clinical settings to treat various human disorders in the future. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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20 pages, 1388 KiB  
Review
In Vitro Model of Human Trophoblast in Early Placentation
by Darina Bačenková, Marianna Trebuňová, Daša Čížková, Radovan Hudák, Erik Dosedla, Alena Findrik-Balogová and Jozef Živčák
Biomedicines 2022, 10(4), 904; https://doi.org/10.3390/biomedicines10040904 - 15 Apr 2022
Cited by 10 | Viewed by 5901
Abstract
The complex process of placental implantation and development affects trophoblast progenitors and uterine cells through the regulation of transcription factors, cytokines, adhesion receptors and their ligands. Differentiation of trophoblast precursors in the trophectoderm of early ontogenesis, caused by the transcription factors, such as [...] Read more.
The complex process of placental implantation and development affects trophoblast progenitors and uterine cells through the regulation of transcription factors, cytokines, adhesion receptors and their ligands. Differentiation of trophoblast precursors in the trophectoderm of early ontogenesis, caused by the transcription factors, such as CDX2, TEAD4, Eomes and GATA3, leads to the formation of cytotrophoblast and syncytiotrophoblast populations. The molecular mechanisms involved in placental formation inside the human body along with the specification and differentiation of trophoblast cell lines are, mostly due to the lack of suitable cell models, not sufficiently elucidated. This review is an evaluation of current technologies, which are used to study the behavior of human trophoblasts and other placental cells, as well as their ability to represent physiological conditions both in vivo and in vitro. An in vitro 3D model with a characteristic phenotype is of great benefit for the study of placental physiology. At the same time, it provides great support for future modeling of placental disease. Full article
(This article belongs to the Special Issue Gynecological Tumor and Placenta Development)
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11 pages, 775 KiB  
Review
Advanced Imaging in Cardiac Amyloidosis
by Dominik Waldmeier, Jan Herzberg, Frank-Peter Stephan, Marcus Seemann and Nisha Arenja
Biomedicines 2022, 10(4), 903; https://doi.org/10.3390/biomedicines10040903 - 15 Apr 2022
Cited by 3 | Viewed by 3093
Abstract
This review serves as a synopsis of multimodality imaging in cardiac amyloidosis (CA), which is a disease characterized by deposition of misfolded protein fragments in the heart. It emphasizes and summarizes the diagnostic possibilities and their prognostic values. In general, echocardiography is the [...] Read more.
This review serves as a synopsis of multimodality imaging in cardiac amyloidosis (CA), which is a disease characterized by deposition of misfolded protein fragments in the heart. It emphasizes and summarizes the diagnostic possibilities and their prognostic values. In general, echocardiography is the first diagnostic tool in patients with an identified systemic disease or unclear left ventricular hypertrophy. Several echocardiographic parameters will raise suspicion and lead to further testing. Cardiac magnetic resonance and scintigraphy with bone avid radiotracers are crucial for diagnosis of CA and even enable a distinction between different subtypes. The subject is illuminated with established guidelines and innovative recent publications to further improve early diagnosis of cardiac amyloidosis in light of current treatment options. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Approaches in Cardiac Amyloidosis)
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14 pages, 303 KiB  
Review
Translational Applications of Extracorporeal Shock Waves in Dental Medicine: A Literature Review
by Abdulmonem Alshihri
Biomedicines 2022, 10(4), 902; https://doi.org/10.3390/biomedicines10040902 - 14 Apr 2022
Cited by 2 | Viewed by 1940
Abstract
Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its [...] Read more.
Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its share of utilizing ESWT in various investigations. This review aimed to provide an up-to-date summary of ESWT use in preclinical and clinical dental medicine. There is growing interest in ESWT use stemming from its non-invasiveness, low cost, and safe qualities in addition to its proven regenerative biostimulating aspects. Targeted tissue and parameters of ESWT delivery continue to be an integral part of successful ESWT treatment to attain the clinical value of the anticipated dose’s effect. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
14 pages, 519 KiB  
Review
Potential Therapeutic Targets and Promising Agents for Combating NAFLD
by Atsushi Umemura, Seita Kataoka, Keiichiro Okuda, Yuya Seko, Kanji Yamaguchi, Michihisa Moriguchi, Takeshi Okanoue and Yoshito Itoh
Biomedicines 2022, 10(4), 901; https://doi.org/10.3390/biomedicines10040901 - 14 Apr 2022
Cited by 7 | Viewed by 2781
Abstract
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. Contrary to the advancements in therapies for viral hepatitis, [...] Read more.
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. Contrary to the advancements in therapies for viral hepatitis, effective treatments remain unestablished for patients with NAFLD. NAFLD, including NASH, is characterized by steatosis, inflammation, hepatic necrosis, and fibrosis. Despite our understanding of its pathophysiology, there are currently no effective treatments for NAFLD. In this review, we provide an update on the known pathophysiological mechanisms involved in the development of NAFLD and the role of hepatic stellate cells, and summarize the potential therapeutic agents, including natural products, for NAFLD. Full article
(This article belongs to the Special Issue NAFLD: From Mechanisms to Therapeutic Approaches)
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16 pages, 11453 KiB  
Article
Liver-Targeted Nanoparticles Facilitate the Bioavailability and Anti-HBV Efficacy of Baicalin In Vitro and In Vivo
by Weiming Xu, Yijun Niu, Xin Ai, Chengjie Xia, Ping Geng, Haiyan Zhu, Wei Zhou, Hai Huang and Xunlong Shi
Biomedicines 2022, 10(4), 900; https://doi.org/10.3390/biomedicines10040900 - 14 Apr 2022
Cited by 5 | Viewed by 1895
Abstract
The anti-hepatitis B virus (HBV) efficacy of baicalin (BA) is mediated by HBV-related hepatocyte nuclear factors (HNFs). However, this efficacy is severely limited by the low bioavailability of BA. Therefore, a novel liver-targeted BA liposome was constructed to promote the bioavailability and antiviral [...] Read more.
The anti-hepatitis B virus (HBV) efficacy of baicalin (BA) is mediated by HBV-related hepatocyte nuclear factors (HNFs). However, this efficacy is severely limited by the low bioavailability of BA. Therefore, a novel liver-targeted BA liposome was constructed to promote the bioavailability and antiviral ability of BA. The results showed that apolipoprotein A1 (ApoA1)–modified liposomes (BAA1) significantly enhanced BA’s cellular uptake and specific distribution in the liver. Furthermore, the substantial inhibitory effects of BAA1 on HBsAg, HBeAg, HBV RNA, and HBV DNA were assessed in HB-infected cells and mice. Western blotting, co-immunoprecipitation, and transcriptomics analysis further revealed that the enhanced anti-HBV efficacy of BAA1 was attributed to the interaction between hepatocyte nuclear factors (HNFs) and estrogen receptors (ERs). Based on the findings, we propose that the ApoA1-modified liposomes aid BA in inhibiting HBV transcription and replication by augmenting its bioavailability and the HNFs–ERs axis. Full article
(This article belongs to the Section Nanomedicine and Nanobiology)
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14 pages, 2345 KiB  
Article
Potential Wound Healing Effect of Gel Based on Chicha Gum, Chitosan, and Mauritia flexuosa Oil
by Maria Onaira Gonçalves Ferreira, Alessandra Braga Ribeiro, Marcia S. Rizzo, Antonia Carla de Jesus Oliveira, Josy Anteveli Osajima, Leticia M. Estevinho and Edson C. Silva-Filho
Biomedicines 2022, 10(4), 899; https://doi.org/10.3390/biomedicines10040899 - 14 Apr 2022
Cited by 6 | Viewed by 2020
Abstract
Wounds are considered a clinically critical issue, and effective treatment will decrease complications, prevent chronic wound formation, and allow rapid healing. The development of products based on naturally occurring materials is an efficient approach to wound healing. Natural polysaccharides can mimic the extracellular [...] Read more.
Wounds are considered a clinically critical issue, and effective treatment will decrease complications, prevent chronic wound formation, and allow rapid healing. The development of products based on naturally occurring materials is an efficient approach to wound healing. Natural polysaccharides can mimic the extracellular matrix and promote cell growth, thus making them attractive for wound healing. In this context, the aim of this work was to produce a gel based on chicha gum, chitosan, and Mauritia flexuosa oil (CGCHO) for wound treatment. TG and DTG analyzed the thermal behavior of the materials, and SEM investigated the surface roughness. The percentages of total phenolic compounds, flavonoids, and antioxidants were determined, presenting a value of 81.811 ± 7.257 µmol gallic acid/g Mauritia flexuosa oil, 57.915 ± 0.305 µmol quercetin/g Mauritia flexuosa oil, and 0.379 mg/mL, respectively. The anti-inflammatory was determined, presenting a value of 10.35 ± 1.46% chicha gum, 16.86 ± 1.00% Mauritia flexuosa oil, 10.17 ± 1.05% CGCHO, and 15.53 ± 0.65% chitosan, respectively. The materials were tested against Gram-negative (Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus) bacteria and a fungus (Candida albicans). The CGCHO formulation showed better antimicrobial activity against Gram-positive bacteria. In addition, an in vivo wound healing study was also performed. After 21 days of treatment, the epidermal re-epithelialization process was observed. CGCHO showed good thermal stability and roughness that can help in cell growth and promote the tissue healing process. In addition to the good results observed for the antimicrobial, antioxidant, anti-inflammatory activities and providing wound healing, they provided the necessary support for the healing process, thus representing a new approach to the wound healing process. Full article
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