Next Issue
Volume 10, September
Previous Issue
Volume 10, July
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Volume 10
Issue 8
share announcement

Cells, Volume 10, Issue 8 (August 2021) – 328 articles

Cover Story (view full-size image): Alzheimer’s disease is a devastating neurodegenerative disease with unknown etiology and for which effective therapies are still lacking: thus far, all clinical trials aimed at testing potential therapies have failed. Subtle cellular impairments involving Ca2+ signaling and mitochondrial function could compromise the ability of the cell to deal with sustained or toxic stimuli and lead, over time, to cellular failure and neurodegeneration. Treatment of mouse neuronal cultures with an inhibitor of the mitochondrial permeability transition pore (PTP) has shown interesting potential in preventing/delaying the loss of mitochondrial membrane potential caused by Ca2+ accumulation within the organelles as a consequence of excitotoxic stimuli. We believe this could be a useful approach to pursue, with the aim of finding a treatment to preserve organellar functionality and cellular integrity. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
16 pages, 1721 KiB  
Review
Roles of IgE and Histamine in Mast Cell Maturation
by Satoshi Tanaka and Kazuyuki Furuta
Cells 2021, 10(8), 2170; https://doi.org/10.3390/cells10082170 - 23 Aug 2021
Cited by 39 | Viewed by 11953
Abstract
Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively [...] Read more.
Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases. Full article
(This article belongs to the Collection Mast Cells in Health and Diseases)
►▼ Show Figures

Graphical abstract

17 pages, 7621 KiB  
Article
Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
by Kyung-Ah Cho, Da-Won Choi, Yu-Hee Kim, Jungwoo Kim, Kyung-Ha Ryu and So-Youn Woo
Cells 2021, 10(8), 2169; https://doi.org/10.3390/cells10082169 - 23 Aug 2021
Cited by 21 | Viewed by 3762
Abstract
Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight [...] Read more.
Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)
►▼ Show Figures

Graphical abstract

15 pages, 6328 KiB  
Article
S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis
by Chien-Chung Huang, Tzu-Ting Tseng, Shan-Chi Liu, Yen-You Lin, Yat-Yin Law, Sung-Lin Hu, Shih-Wei Wang, Chun-Hao Tsai and Chih-Hsin Tang
Cells 2021, 10(8), 2168; https://doi.org/10.3390/cells10082168 - 23 Aug 2021
Cited by 31 | Viewed by 4340
Abstract
Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 [...] Read more.
Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment. Full article
►▼ Show Figures

Figure 1

18 pages, 1649 KiB  
Article
Causes of Anemia in Polish Older Population—Results from the PolSenior Study
by Arkadiusz Styszyński, Jerzy Chudek, Małgorzata Mossakowska, Krzysztof Lewandowski, Monika Puzianowska-Kuźnicka, Alicja Klich-Rączka, Andrzej Więcek and Katarzyna Wieczorowska-Tobis
Cells 2021, 10(8), 2167; https://doi.org/10.3390/cells10082167 - 22 Aug 2021
Cited by 9 | Viewed by 4221
Abstract
Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific [...] Read more.
Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific criteria for the diagnosis of functional nutritional deficiency related to anemia are necessary. We examined the nationally representative sample of Polish seniors. Complete blood count, serum iron, ferritin, vitamin B12, folate, and renal parameters were assessed in 3452 (1632 women, 1820 men) participants aged above 64. Cut-off points for nutritional deficiencies were determined based on the WHO criteria (method-A), lower 2.5 percentile of the studied population (method-B), and receiver operating characteristic (ROC) analysis (method-C). Method-A leads to an overestimation of the prevalence of vitamin B12 and folate deficiency, while method-B to their underestimation with over 50% of unexplained anemia. Based on method-C, anemia was classified as nutritional in 55.9%. In 22.3% of cases, reasons for anemia remained unexplained, the other 21.8% were related to CKD or AI. Mild cases were less common in IDA, and more common in non-deficiency anemia. Serum folate had an insignificant impact on anemia. It is necessary to adopt the age-specific criteria for nutrient deficiency in an old population. Full article
(This article belongs to the Collection Advances in Red Blood Cells Research)
►▼ Show Figures

Figure 1

16 pages, 3669 KiB  
Article
Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy
by Yat-Ping Tsui, Guy Lam, Kenneth Lap-Kei Wu, Maximilian Tak-Sui Li, Kin-Wai Tam, Daisy Kwok-Yan Shum and Ying-Shing Chan
Cells 2021, 10(8), 2166; https://doi.org/10.3390/cells10082166 - 22 Aug 2021
Cited by 4 | Viewed by 3223
Abstract
Transplantation of oligodendrocyte precursors (OPs) is potentially therapeutic for myelin disorders but a safe and accessible cell source remains to be identified. Here we report a two-step protocol for derivation of highly enriched populations of OPs from bone marrow stromal cells of young [...] Read more.
Transplantation of oligodendrocyte precursors (OPs) is potentially therapeutic for myelin disorders but a safe and accessible cell source remains to be identified. Here we report a two-step protocol for derivation of highly enriched populations of OPs from bone marrow stromal cells of young adult rats (aMSCs). Neural progenitors among the aMSCs were expanded in non-adherent sphere-forming cultures and subsequently directed along the OP lineage with the use of glial-inducing growth factors. Immunocytochemical and flow cytometric analyses of these cells confirmed OP-like expression of Olig2, PDGFRα, NG2, and Sox10. OPs so derived formed compact myelin both in vitro, as in co-culture with purified neurons, and in vivo, following transplantation into the corpus callosum of neonatal shiverer mice. Not only did the density of myelinated axons in the corpus callosum of recipient shiverer mice reach levels comparable to those in age-matched wild-type mice, but the mean lifespan of recipient shiverer mice also far exceeded those of non-recipient shiverer mice. Our results thus promise progress in harnessing the OP-generating potential of aMSCs towards cell therapy for myelin disorders. Full article
(This article belongs to the Section Cells of the Nervous System)
►▼ Show Figures

Graphical abstract

19 pages, 4864 KiB  
Article
Mesenchymal Stromal Cell Differentiation for Generating Cartilage and Bone-Like Tissues In Vitro
by Graziana Monaco, Yann D. Ladner, Alicia J. El Haj, Nicholas R. Forsyth, Mauro Alini and Martin J. Stoddart
Cells 2021, 10(8), 2165; https://doi.org/10.3390/cells10082165 - 22 Aug 2021
Cited by 6 | Viewed by 4192
Abstract
In the field of tissue engineering, progress has been made towards the development of new treatments for cartilage and bone defects. However, in vitro culture conditions for human bone marrow mesenchymal stromal cells (hBMSCs) have not yet been fully defined. To improve our [...] Read more.
In the field of tissue engineering, progress has been made towards the development of new treatments for cartilage and bone defects. However, in vitro culture conditions for human bone marrow mesenchymal stromal cells (hBMSCs) have not yet been fully defined. To improve our understanding of cartilage and bone in vitro differentiation, we investigated the effect of culture conditions on hBMSC differentiation. We hypothesized that the use of two different culture media including specific growth factors, TGFβ1 or BMP2, as well as low (2% O2) or high (20% O2) oxygen tension, would improve the chondrogenic and osteogenic potential, respectively. Chondrogenic and osteogenic differentiation of hBMSCs isolated from multiple donors and expanded under the same conditions were directly compared. Chondrogenic groups showed a notable upregulation of chondrogenic markers compared with osteogenic groups. Greater sGAG production and deposition, and collagen type II and I accumulation occurred for chondrogenic groups. Chondrogenesis at 2% O2 significantly reduced ALP gene expression and reduced type I collagen deposition, producing a more stable and less hypertrophic chondrogenic phenotype. An O2 tension of 2% did not inhibit osteogenic differentiation at the protein level but reduced ALP and OC gene expression. An upregulation of ALP and OC occurred during osteogenesis in BMP2 containing media under 20% O2; BMP2 free osteogenic media downregulated ALP and also led to higher sGAG release. A higher mineralization was observed in the presence of BMP2 during osteogenesis. This study demonstrates how the modulation of O2 tension, combined with tissue-specific growth factors and media composition can be tailored in vitro to promote chondral or endochondral differentiation while using the same donor cell population. Full article
(This article belongs to the Special Issue Cell Therapies in Orthopaedics)
►▼ Show Figures

Figure 1

18 pages, 1056 KiB  
Review
Triggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis
by Pierre-Alexandre Piec, Vincent Pons and Serge Rivest
Cells 2021, 10(8), 2164; https://doi.org/10.3390/cells10082164 - 22 Aug 2021
Cited by 5 | Viewed by 4638
Abstract
Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate [...] Read more.
Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues. Full article
►▼ Show Figures

Figure 1

16 pages, 2906 KiB  
Article
The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress
by Nilson Carlos Ferreira Junior, Maurício dos Santos Pereira, Nour Francis, Paola Ramirez, Paula Martorell, Florencia González-Lizarraga, Bruno Figadère, Rosana Chehin, Elaine Del Bel, Rita Raisman-Vozari and Patrick Pierre Michel
Cells 2021, 10(8), 2163; https://doi.org/10.3390/cells10082163 - 22 Aug 2021
Cited by 12 | Viewed by 3672
Abstract
We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of [...] Read more.
We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner. Full article
(This article belongs to the Collection Feature Papers in 'Cells of the Nervous System' Section)
►▼ Show Figures

Figure 1

31 pages, 8554 KiB  
Article
Proteomic Analysis of Hydromethylthionine in the Line 66 Model of Frontotemporal Dementia Demonstrates Actions on Tau-Dependent and Tau-Independent Networks
by Karima Schwab, Valeria Melis, Charles R. Harrington, Claude M. Wischik, Mandy Magbagbeolu, Franz Theuring and Gernot Riedel
Cells 2021, 10(8), 2162; https://doi.org/10.3390/cells10082162 - 22 Aug 2021
Cited by 3 | Viewed by 4160
Abstract
Abnormal aggregation of tau is the pathological hallmark of tauopathies including frontotemporal dementia (FTD). We have generated tau-transgenic mice that express the aggregation-prone P301S human tau (line 66). These mice present with early-onset, high tau load in brain and FTD-like behavioural deficiencies. Several [...] Read more.
Abnormal aggregation of tau is the pathological hallmark of tauopathies including frontotemporal dementia (FTD). We have generated tau-transgenic mice that express the aggregation-prone P301S human tau (line 66). These mice present with early-onset, high tau load in brain and FTD-like behavioural deficiencies. Several of these behavioural phenotypes and tau pathology are reversed by treatment with hydromethylthionine but key pathways underlying these corrections remain elusive. In two proteomic experiments, line 66 mice were compared with wild-type mice and then vehicle and hydromethylthionine treatments of line 66 mice were compared. The brain proteome was investigated using two-dimensional electrophoresis and mass spectrometry to identify protein networks and pathways that were altered due to tau overexpression or modified by hydromethylthionine treatment. Overexpression of mutant tau induced metabolic/mitochondrial dysfunction, changes in synaptic transmission and in stress responses, and these functions were recovered by hydromethylthionine. Other pathways, such as NRF2, oxidative phosphorylation and protein ubiquitination were activated by hydromethylthionine, presumably independent of its function as a tau aggregation inhibitor. Our results suggest that hydromethylthionine recovers cellular activity in both a tau-dependent and a tau-independent fashion that could lead to a wide-spread improvement of homeostatic function in the FTD brain. Full article
(This article belongs to the Collection Tau Protein in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

45 pages, 6239 KiB  
Review
Insight into Hypoxia Stemness Control
by Miriam Di Mattia, Annunziata Mauro, Maria Rita Citeroni, Beatrice Dufrusine, Alessia Peserico, Valentina Russo, Paolo Berardinelli, Enrico Dainese, Annamaria Cimini and Barbara Barboni
Cells 2021, 10(8), 2161; https://doi.org/10.3390/cells10082161 - 22 Aug 2021
Cited by 19 | Viewed by 6383
Abstract
Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrinsic factors that can control stem [...] Read more.
Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrinsic factors that can control stem cell fate. One key factor controlling stem cell phenotype is oxygen (O2). Several pieces of evidence demonstrated that the complexity of reproducing O2 physiological tensions and gradients in culture is responsible for defective stem cell behavior in vitro and after transplantation. This evidence is still worsened by considering that stem cells are conventionally incubated under non-physiological air O2 tension (21%). Therefore, the study of mechanisms and signaling activated at lower O2 tension, such as those existing under native microenvironments (referred to as hypoxia), represent an effective strategy to define if O2 is essential in preserving naïve stemness potential as well as in modulating their differentiation. Starting from this premise, the goal of the present review is to report the status of the art about the link existing between hypoxia and stemness providing insight into the factors/molecules involved, to design targeted strategies that, recapitulating naïve O2 signals, enable towards the therapeutic use of stem cell for tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Feature Papers in Stem Cells)
►▼ Show Figures

Figure 1

18 pages, 603 KiB  
Review
The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism
by Guoxun Chen
Cells 2021, 10(8), 2160; https://doi.org/10.3390/cells10082160 - 21 Aug 2021
Cited by 18 | Viewed by 4444
Abstract
The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. [...] Read more.
The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA’s physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided. Full article
(This article belongs to the Special Issue Retinoic Acid and Retinoid X Receptors)
►▼ Show Figures

Graphical abstract

15 pages, 1582 KiB  
Article
Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage
by Elisa Balboa, Tamara Marín, Juan Esteban Oyarzún, Pablo S. Contreras, Robert Hardt, Thea van den Bosch, Alejandra R. Alvarez, Boris Rebolledo-Jaramillo, Andres D. Klein, Dominic Winter and Silvana Zanlungo
Cells 2021, 10(8), 2159; https://doi.org/10.3390/cells10082159 - 21 Aug 2021
Cited by 10 | Viewed by 5051
Abstract
Niemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of [...] Read more.
Niemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of the liver damage remains unclear. In this study, hepatocytes derived from wild type and Npc1−/− mice were analyzed by mass spectrometry (MS)-based proteomics in conjunction with bioinformatic analysis. We identified 3832 proteins: 416 proteins had a p-value smaller than 0.05, of which 37% (n = 155) were considered differentially expressed proteins (DEPs), 149 of them were considered upregulated, and 6 were considered downregulated. We focused the analysis on pathways related to NPC pathogenic mechanisms, finding that the most significant changes in expression levels occur in proteins that function in the pathways of liver damage, lipid metabolism, and inflammation. Moreover, in the group of DEPs, 30% (n = 47) were identified as lysosomal proteins and 7% (n = 10) were identified as mitochondrial proteins. Importantly, we found that lysosomal DEPs, including CTSB/D/Z, LIPA, DPP7 and GLMP, and mitocondrial DEPs, AKR1B10, and VAT1 had been connected with liver fibrosis, damage, and steatosis in previous studies, validiting our dataset. Our study found potential therapeutic targets for the treatment of liver damage in NPCD. Full article
(This article belongs to the Collection Deciphering the Proteome in Cell Biology and Diseases)
►▼ Show Figures

Graphical abstract

30 pages, 1957 KiB  
Review
HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits
by Kristen A. McLaurin, Michael Harris, Victor Madormo, Steven B. Harrod, Charles F. Mactutus and Rosemarie M. Booze
Cells 2021, 10(8), 2158; https://doi.org/10.3390/cells10082158 - 21 Aug 2021
Cited by 23 | Viewed by 5100
Abstract
Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations [...] Read more.
Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function. Full article
(This article belongs to the Special Issue The Past, Present and Future of NeuroHIV: A Perspective to A Cure)
►▼ Show Figures

Figure 1

15 pages, 1322 KiB  
Review
EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?
by Paul Hofman
Cells 2021, 10(8), 2157; https://doi.org/10.3390/cells10082157 - 21 Aug 2021
Cited by 5 | Viewed by 3591
Abstract
The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different [...] Read more.
The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different treatments in these patients. Currently, the choice of one or another of these treatments mainly depends on the results of immunohistochemistry for PD-L1 and of the status of EGFR and ALK. This new development has led to the setup of different analyses for clinical and molecular pathology laboratories, which have had to rapidly integrate a number of new challenges into daily practice and to establish new organization for decision making. This review outlines the impact of the management of biological samples in laboratories and discusses perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Lung Cancers)
►▼ Show Figures

Figure 1

34 pages, 785 KiB  
Review
Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review
by Katya Rubia, Samuel Westwood, Pascal-M. Aggensteiner and Daniel Brandeis
Cells 2021, 10(8), 2156; https://doi.org/10.3390/cells10082156 - 21 Aug 2021
Cited by 43 | Viewed by 14702
Abstract
This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback [...] Read more.
This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment. Full article
(This article belongs to the Special Issue Neuroplasticity of Central Nervous System in Health and Disease)
►▼ Show Figures

Figure 1

13 pages, 684 KiB  
Review
Glucocorticoid-Induced Leucine Zipper (GILZ) in Cardiovascular Health and Disease
by Donato Cappetta, Oxana Bereshchenko, Eleonora Cianflone, Francesco Rossi, Carlo Riccardi, Daniele Torella, Liberato Berrino, Konrad Urbanek, Antonella De Angelis and Stefano Bruscoli
Cells 2021, 10(8), 2155; https://doi.org/10.3390/cells10082155 - 21 Aug 2021
Cited by 5 | Viewed by 3505
Abstract
Glucocorticoids (GCs) are essential in regulating functions and homeostasis in many biological systems and are extensively used to treat a variety of conditions associated with immune/inflammatory processes. GCs are among the most powerful drugs for the treatment of autoimmune and inflammatory diseases, but [...] Read more.
Glucocorticoids (GCs) are essential in regulating functions and homeostasis in many biological systems and are extensively used to treat a variety of conditions associated with immune/inflammatory processes. GCs are among the most powerful drugs for the treatment of autoimmune and inflammatory diseases, but their long-term usage is limited by severe adverse effects. For this reason, to envision new therapies devoid of typical GC side effects, research has focused on expanding the knowledge of cellular and molecular effects of GCs. GC-induced leucine zipper (GILZ) is a GC-target protein shown to mediate several actions of GCs, including inhibition of the NF-κB and MAPK pathways. GILZ expression is not restricted to immune cells, and it has been shown to play a regulatory role in many organs and tissues, including the cardiovascular system. Research on the role of GILZ on endothelial cells has demonstrated its ability to modulate the inflammatory cascade, resulting in a downregulation of cytokines, chemokines, and cellular adhesion molecules. GILZ also has the capacity to protect myocardial cells, as its deletion makes the heart, after a deleterious stimulus, more susceptible to apoptosis, immune cell infiltration, hypertrophy, and impaired function. Despite these advances, we have only just begun to appreciate the relevance of GILZ in cardiovascular homeostasis and dysfunction. This review summarizes the current understanding of the role of GILZ in modulating biological processes relevant to cardiovascular biology. Full article
(This article belongs to the Collection Glucocorticoid-Induced Proteins Annexin A1 and GILZ in Inflammation)
►▼ Show Figures

Figure 1

21 pages, 1473 KiB  
Review
Plectin-Mediated Intermediate Filament Functions: Why Isoforms Matter
by Gerhard Wiche
Cells 2021, 10(8), 2154; https://doi.org/10.3390/cells10082154 - 21 Aug 2021
Cited by 24 | Viewed by 5662
Abstract
This essay focuses on the role of plectin and its various isoforms in mediating intermediate filament (IF) network functions. It is based on previous studies that provided comprehensive evidence for a concept where plectin acts as an IF recruiter, and plectin-mediated IF networking [...] Read more.
This essay focuses on the role of plectin and its various isoforms in mediating intermediate filament (IF) network functions. It is based on previous studies that provided comprehensive evidence for a concept where plectin acts as an IF recruiter, and plectin-mediated IF networking and anchoring are key elements in IF function execution. Here, plectin’s global role as modulator of IF functionality is viewed from different perspectives, including the mechanical stabilization of IF networks and their docking platforms, contribution to cellular viscoelasticity and mechanotransduction, compartmentalization and control of the actomyosin machinery, connections to the microtubule system, and mechanisms and specificity of isoform targeting. Arguments for IF networks and plectin acting as mutually dependent partners are also given. Lastly, a working model is presented that describes a unifying mechanism underlying how plectin–IF networks mechanically control and propagate actomyosin-generated forces, affect microtubule dynamics, and contribute to mechanotransduction. Full article
(This article belongs to the Special Issue Plectin in Health and Disease)
►▼ Show Figures

Figure 1

14 pages, 564 KiB  
Review
Cell Ferroptosis: New Mechanism and New Hope for Retinitis Pigmentosa
by Ming Yang, Kwok-Fai So, Wai-Ching Lam and Amy Cheuk Yin Lo
Cells 2021, 10(8), 2153; https://doi.org/10.3390/cells10082153 - 21 Aug 2021
Cited by 16 | Viewed by 5012
Abstract
Retinitis pigmentosa (RP) is a leading cause of inherited retinal degeneration, with more than 60 gene mutations. Despite the genetic heterogenicity, photoreceptor cell damage remains the hallmark of RP pathology. As a result, RP patients usually suffer from reduced night vision, loss of [...] Read more.
Retinitis pigmentosa (RP) is a leading cause of inherited retinal degeneration, with more than 60 gene mutations. Despite the genetic heterogenicity, photoreceptor cell damage remains the hallmark of RP pathology. As a result, RP patients usually suffer from reduced night vision, loss of peripheral vision, decreased visual acuity, and impaired color perception. Although photoreceptor cell death is the primary outcome of RP, the underlying mechanisms are not completely elucidated. Ferroptosis is a novel programmed cell death, with characteristic iron overload and lipid peroxidation. Recent studies, using in vitro and in vivo RP models, discovered the involvement of ferroptosis-associated cell death, suggesting a possible new mechanism for RP pathogenesis. In this review, we discuss the association between ferroptosis and photoreceptor cell damage, and its implication in the pathogenesis of RP. We propose that ferroptotic cell death not only opens up a new research area in RP, but may also serve as a novel therapeutic target for RP. Full article
(This article belongs to the Special Issue Cell Death Signaling of Ferroptosis)
►▼ Show Figures

Graphical abstract

16 pages, 2598 KiB  
Article
New Insights into Xenotransplantation for Cartilage Repair: Porcine Multi-Genetically Modified Chondrocytes as a Promising Cell Source
by Hanna Tritschler, Konrad Fischer, Jochen Seissler, Jörg Fiedler, Rebecca Halbgebauer, Markus Huber-Lang, Angelika Schnieke and Rolf E. Brenner
Cells 2021, 10(8), 2152; https://doi.org/10.3390/cells10082152 - 20 Aug 2021
Cited by 8 | Viewed by 3399
Abstract
Transplantation of xenogenic porcine chondrocytes could represent a future strategy for the treatment of human articular cartilage defects. Major obstacles are humoral and cellular rejection processes triggered by xenogenic epitopes like α-1,3-Gal and Neu5Gc. Besides knockout (KO) of genes responsible for the biosynthesis [...] Read more.
Transplantation of xenogenic porcine chondrocytes could represent a future strategy for the treatment of human articular cartilage defects. Major obstacles are humoral and cellular rejection processes triggered by xenogenic epitopes like α-1,3-Gal and Neu5Gc. Besides knockout (KO) of genes responsible for the biosynthesis of respective epitopes (GGTA1 and CMAH), transgenic expression of human complement inhibitors and anti-apoptotic as well as anti-inflammatory factors (CD46, CD55, CD59, TNFAIP3 and HMOX1) could synergistically prevent hyperacute xenograft rejection. Therefore, chondrocytes from different strains of single- or multi-genetically modified pigs were characterized concerning their protection from xenogeneic complement activation. Articular chondrocytes were isolated from the knee joints of WT, GalTKO, GalT/CMAH-KO, human CD59/CD55//CD46/TNFAIP3/HMOX1-transgenic (TG), GalTKO/TG and GalT/CMAHKO/TG pigs. The tissue-specific effectiveness of the genetic modifications was tested on gene, protein and epitope expression level or by functional assays. After exposure to 20% and 40% normal human serum (NHS), deposition of C3b/iC3b/C3c and formation of the terminal complement complex (TCC, C5b-9) was quantified by specific cell ELISAs, and generation of the anaphylatoxin C5a by ELISA. Chondrocyte lysis was analyzed by Trypan Blue Exclusion Assay. In all respective KO variants, the absence of α -1,3-Gal and Neu5Gc epitope was verified by FACS analysis. In chondrocytes derived from TG animals, expression of CD55 and CD59 could be confirmed on gene and protein level, TNFAIP3 on gene expression level as well as by functional assays and CD46 only on gene expression level whereas transgenic HMOX1 expression was not evident. Complement activation in the presence of NHS indicated mainly effective although incomplete protection against C3b/iC3b/C3c deposition, C5a-generation and C5b-9 formation being lowest in single GalTKO. Chondrocyte viability under exposure to NHS was significantly improved even by single GalTKO and completely preserved by all other variants including TG chondrocytes without KO of xenoepitopes. Full article
(This article belongs to the Special Issue Cell Therapies in Orthopaedics)
►▼ Show Figures

Figure 1

14 pages, 4849 KiB  
Article
Inhibition of STAT3/PD-L1 and Activation of miR193a-5p Are Critically Involved in Apoptotic Effect of Compound K in Prostate Cancer Cells
by Jae-Hee Lee, Dae-Young Lee, Hyo-Jung Lee, Eunji Im, Deok-Yong Sim, Ji-Eon Park, Woon-Yi Park, Bum-Sang Shim and Sung-Hoon Kim
Cells 2021, 10(8), 2151; https://doi.org/10.3390/cells10082151 - 20 Aug 2021
Cited by 14 | Viewed by 3736
Abstract
Since the signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) signaling plays an important role in tumor-immune microenvironments, in the present study, the role of STAT3/PD-L1 signaling in the apoptotic mechanism of an active ginseng saponin metabolite compound K (CK) [...] Read more.
Since the signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) signaling plays an important role in tumor-immune microenvironments, in the present study, the role of STAT3/PD-L1 signaling in the apoptotic mechanism of an active ginseng saponin metabolite compound K (CK) was investigated in human prostate cancer cells. Here, CK exerted significant cytotoxicity without hurting RWPE1 normal prostate epithelial cells, increased sub-G1 and cleavage of Poly ADP-ribose polymerase (PARP) and attenuated the expression of pro-PARP and Pro-cysteine aspartyl-specific protease3 (pro-caspase-3) in LANCap, PC-3 and DU145 cells. Further, CK attenuated the expression of p-STAT3 and PD-L1 in DU145 cells along with disrupted the binding of STAT3 to PD-L1. Furthermore, CK effectively abrogated the expression of p-STAT3 and PD-L1 in interferon-gamma (INF-γ)-stimulated DU145cells. Additionally, CK suppressed the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin 6 (IL-6) and interleukin 10 (IL-10) as immune escape-related genes in DU145 cells. Likewise, as STAT3 targets genes, the expression of CyclinD1, c-Myc and B-cell lymphoma-extra-large (Bcl-xL) was attenuated in CK-treated DU145 cells. Notably, CK upregulated the expression of microRNA193a-5p (miR193a-5p) in DU145 cells. Consistently, miR193a-5p mimic suppressed p-STAT3, PD-L1 and pro-PARP, while miR193a-5p inhibitor reversed the ability of CK to attenuate the expression of p-STAT3, PD-L1 and pro-PARP in DU145 cells. Taken together, these findings support evidence that CK induces apoptosis via the activation of miR193a-5p and inhibition of PD-L1 and STAT3 signaling in prostate cancer cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Modulation of Tumor Immune Microenvironment)
►▼ Show Figures

Figure 1

10 pages, 3436 KiB  
Systematic Review
Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis
by Walter Masson, Augusto Lavalle-Cobo and Juan Patricio Nogueira
Cells 2021, 10(8), 2150; https://doi.org/10.3390/cells10082150 - 20 Aug 2021
Cited by 49 | Viewed by 3949
Abstract
(1) Sodium–glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a [...] Read more.
(1) Sodium–glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a systematic review and meta-analysis of SGLT2-i therapy on T2D patients, reporting data on changes in EAT after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random effects or fixed effects model meta-analysis was then applied. (3) Results: A total of three studies (n = 64 patients with SGLT2-i, n = 62 with standard therapy) were included in the final analysis. SGLT2 inhibitors reduced EAT (SMD: −0.82 (−1.49; −0.15); p < 0.0001). An exploratory analysis showed that HbA1c was significantly reduced with SGLT2-i use, while body mass index was not significantly reduced with this drug. (4) Conclusions: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with SGLT2-i treatment. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Ectopic Fat Deposition in the Heart)
►▼ Show Figures

Figure 1

18 pages, 4349 KiB  
Article
FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish
by Zhi Feng, Chenyu Lin, Limei Tu, Ming Su, Chunyu Song, Shengnan Liu, Michael Edbert Suryanto, Chung-Der Hsiao and Li Li
Cells 2021, 10(8), 2149; https://doi.org/10.3390/cells10082149 - 20 Aug 2021
Cited by 2 | Viewed by 3376
Abstract
Hematopoietic stem cells (HSCs) are a specialized subset of cells with self-renewal and multilineage differentiation potency, which are essential for their function in bone marrow or umbilical cord blood transplantation to treat blood disorders. Expanding the hematopoietic stem and progenitor cells (HSPCs) ex [...] Read more.
Hematopoietic stem cells (HSCs) are a specialized subset of cells with self-renewal and multilineage differentiation potency, which are essential for their function in bone marrow or umbilical cord blood transplantation to treat blood disorders. Expanding the hematopoietic stem and progenitor cells (HSPCs) ex vivo is essential to understand the HSPCs-based therapies potency. Here, we established a screening system in zebrafish by adopting an FDA-approved drug library to identify candidates that could facilitate HSPC expansion. To date, we have screened 171 drugs of 7 categories, including antibacterial, antineoplastic, glucocorticoid, NSAIDS, vitamins, antidepressant, and antipsychotic drugs. We found 21 drugs that contributed to HSPCs expansion, 32 drugs’ administration caused HSPCs diminishment and 118 drugs’ treatment elicited no effect on HSPCs amplification. Among these drugs, we further investigated the vitamin drugs ergocalciferol and panthenol, taking advantage of their acceptability, limited side-effects, and easy delivery. These two drugs, in particular, efficiently expanded the HSPCs pool in a dose-dependent manner. Their application even mitigated the compromised hematopoiesis in an ikzf1−/− mutant. Taken together, our study implied that the larval zebrafish is a suitable model for drug repurposing of effective molecules (especially those already approved for clinical use) that can facilitate HSPCs expansion. Full article
(This article belongs to the Special Issue Fishing for Health: Zebrafish Models of Human Disease)
►▼ Show Figures

Figure 1

21 pages, 1459 KiB  
Review
Functional Roles of FGF Signaling in Early Development of Vertebrate Embryos
by Vijay Kumar, Ravi Shankar Goutam, Soochul Park, Unjoo Lee and Jaebong Kim
Cells 2021, 10(8), 2148; https://doi.org/10.3390/cells10082148 - 20 Aug 2021
Cited by 25 | Viewed by 8394
Abstract
Fibroblast growth factors (FGFs) comprise a large family of growth factors, regulating diverse biological processes including cell proliferation, migration, and differentiation. Each FGF binds to a set of FGF receptors to initiate certain intracellular signaling molecules. Accumulated evidence suggests that in early development [...] Read more.
Fibroblast growth factors (FGFs) comprise a large family of growth factors, regulating diverse biological processes including cell proliferation, migration, and differentiation. Each FGF binds to a set of FGF receptors to initiate certain intracellular signaling molecules. Accumulated evidence suggests that in early development and adult state of vertebrates, FGFs also play exclusive and context dependent roles. Although FGFs have been the focus of research for therapeutic approaches in cancer, cardiovascular disease, and metabolic syndrome, in this review, we mainly focused on their role in germ layer specification and axis patterning during early vertebrate embryogenesis. We discussed the functional roles of FGFs and their interacting partners as part of the gene regulatory network for germ layer specification, dorsal–ventral (DV), and anterior-posterior (AP) patterning. Finally, we briefly reviewed the regulatory molecules and pharmacological agents discovered that may allow modulation of FGF signaling in research. Full article
(This article belongs to the Collection Fibroblast Growth Factors: Pathophysiology and Therapeutics)
►▼ Show Figures

Figure 1

15 pages, 5498 KiB  
Article
Identifying the Effects of Reactive Oxygen Species on Mitochondrial Dynamics and Cytoskeleton Stability in Dictyostelium discoideum
by Evan Downs, Amber D. Bottrell and Kari Naylor
Cells 2021, 10(8), 2147; https://doi.org/10.3390/cells10082147 - 20 Aug 2021
Cited by 4 | Viewed by 2727
Abstract
Defects in mitochondrial dynamics, fission, fusion, and motility have been implicated in the pathogenesis of multiple neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Charcot–Marie–Tooth disease. Another key feature of neurodegeneration is the increase in reactive oxygen species (ROS). Previous work [...] Read more.
Defects in mitochondrial dynamics, fission, fusion, and motility have been implicated in the pathogenesis of multiple neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Charcot–Marie–Tooth disease. Another key feature of neurodegeneration is the increase in reactive oxygen species (ROS). Previous work has shown that the cytoskeleton, in particular the microtubules, and ROS generated by rotenone significantly regulate mitochondrial dynamics in Dictyostelium discoideum. The goal of this project is to study the effects of ROS on mitochondrial dynamics within our model organism D. discoideum to further understand the underlying issues that are the root of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. We chose three likely ROS inducers, cumene hydroperoxide, hydroxylamine hydrochloride, and Antimycin A. Our work demonstrates that alteration of the microtubule cytoskeleton is not required to alter dynamics in response to ROS and there is no easy way to predict how mitochondrial dynamics will be altered based on which ROS generator is used. This research contributes to the better understanding of the cellular mechanisms that induce the pathogenesis of incurable neurodegenerative diseases with the hope that it will translate into developing new and more effective treatments for patients afflicted by them. Full article
(This article belongs to the Special Issue Nonmammalian Models for Neurodegenerative and Neurological Disorders)
►▼ Show Figures

Figure 1

13 pages, 3132 KiB  
Article
Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
by Andreas Schmid, Ann-Kathrin Vlacil, Jutta Schuett, Thomas Karrasch, Bernhard Schieffer, Andreas Schäffler and Karsten Grote
Cells 2021, 10(8), 2146; https://doi.org/10.3390/cells10082146 - 20 Aug 2021
Cited by 6 | Viewed by 3433
Abstract
The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on [...] Read more.
The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin (Il)-6 and the tumor necrosis factor (Tnf)-α, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules Vcam-1 and Icam-1. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia. Full article
►▼ Show Figures

Graphical abstract

10 pages, 288 KiB  
Editorial
Modeling Extracellular Matrix-Cell Interactions in Lung Repair and Chronic Disease
by Tillie Louise Hackett and Emmanuel Twumasi Osei
Cells 2021, 10(8), 2145; https://doi.org/10.3390/cells10082145 - 20 Aug 2021
Cited by 23 | Viewed by 3998
Abstract
The lung extracellular matrix (ECM) is a complex and dynamic mixture of fibrous proteins (collagen, elastin), glycoproteins (fibronectin, laminin), glycosaminoglycans (heparin, hyaluronic acid) and proteoglycans (perlecan, versican), that are essential for normal lung development and organ health [...] Full article
(This article belongs to the Special Issue Modeling Extracellular Matrix-Cell Interactions in Lung Repair and Chronic Disease)
3 pages, 186 KiB  
Editorial
Stem Cells to the Rescue: Development and Application of Cell-Based Therapy for Microvascular Repair
by Lilach O. Lerman and Amir Lerman
Cells 2021, 10(8), 2144; https://doi.org/10.3390/cells10082144 - 20 Aug 2021
Viewed by 1888
Abstract
The microcirculation includes an invisible network of micro-vessels that are up to a few hundred microns in diameter [...] Full article
(This article belongs to the Special Issue Stem Cells to the Rescue: Development and Application of Cell-Based Therapy for Microvascular Repair)
16 pages, 5647 KiB  
Article
Single-Cell Transcriptomics Reveals Core Regulatory Programs That Determine the Heterogeneity of Circulating and Tissue-Resident Memory CD8+ T Cells
by Yao Chen, Jian Shen, Moujtaba Y. Kasmani, Paytsar Topchyan and Weiguo Cui
Cells 2021, 10(8), 2143; https://doi.org/10.3390/cells10082143 - 20 Aug 2021
Cited by 20 | Viewed by 6893
Abstract
During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. T central memory (TCM), T effector memory (TEM), and long-lived effector (LLE) cells are circulating memory populations with distinct plasticity, migration patterns, and effector functions. Tissue-resident [...] Read more.
During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. T central memory (TCM), T effector memory (TEM), and long-lived effector (LLE) cells are circulating memory populations with distinct plasticity, migration patterns, and effector functions. Tissue-resident memory (TRM) cells permanently reside in the frontline sites of pathogen entry and provide tissue-specific protection upon reinfection. Here, using single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq, we examined the different and shared transcriptomes and regulators of TRM cells with other circulating memory populations. Furthermore, we identified heterogeneity within the TRM pool from small intestine and novel transcriptional regulators that may control the phenotypic and functional heterogeneity of TRM cells during acute infection. Our findings provide a resource for future studies to identify novel pathways for enhancing vaccination and immunotherapeutic approaches. Full article
(This article belongs to the Special Issue Tissue-Resident Memory T Cells)
►▼ Show Figures

Figure 1

19 pages, 2306 KiB  
Review
The Role of microRNAs in Pulp Inflammation
by José Luis Muñoz-Carrillo, Silverio Jafet Vázquez-Alcaraz, Jazmín Monserrat Vargas-Barbosa, Luis Guillermo Ramos-Gracia, Israel Alvarez-Barreto, Alejandro Medina-Quiroz and Karla Karina Díaz-Huerta
Cells 2021, 10(8), 2142; https://doi.org/10.3390/cells10082142 - 20 Aug 2021
Cited by 17 | Viewed by 6898
Abstract
The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different [...] Read more.
The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different microRNAs during pulp inflammation has been previously documented. MicroRNAs (miRNAs) are endogenous small molecules involved in the transcription of genes that regulate the immune system and the inflammatory response. They are present in cellular and physiological functions, as well as in the pathogenesis of human diseases, becoming potential biomarkers for diagnosis, prognosis, monitoring, and safety. Previous studies have evidenced the different roles played by miRNAs in proinflammatory, anti-inflammatory, and immunological phenomena in the dental pulp, highlighting specific key functions of pulp pathology. This systematized review aims to provide an understanding of the role of the different microRNAs detected in the pulp and their effects on the expression of the different target genes that are involved during pulp inflammation. Full article
(This article belongs to the Collection Regulatory Functions of microRNAs)
►▼ Show Figures

Figure 1

13 pages, 2530 KiB  
Article
SNAP47 Interacts with ATG14 to Promote VP1 Conjugation and CVB3 Propagation
by Pinhao Xiang, Yasir Mohamud and Honglin Luo
Cells 2021, 10(8), 2141; https://doi.org/10.3390/cells10082141 - 20 Aug 2021
Cited by 4 | Viewed by 3495
Abstract
Coxsackievirus B3 (CVB3), an enterovirus (EV) in the family of Picornaviridae, is a global human pathogen for which effective antiviral treatments and vaccines are lacking. Previous research demonstrated that EV-D68 downregulated the membrane fusion protein SNAP47 (synaptosome associated protein 47) and SNAP47 [...] Read more.
Coxsackievirus B3 (CVB3), an enterovirus (EV) in the family of Picornaviridae, is a global human pathogen for which effective antiviral treatments and vaccines are lacking. Previous research demonstrated that EV-D68 downregulated the membrane fusion protein SNAP47 (synaptosome associated protein 47) and SNAP47 promoted EV-D68 replication via regulating autophagy. In the current study, we investigated the interplay between CVB3 and cellular SNAP47 using HEK293T/HeLa cell models. We showed that, upon CVB3 infection, protein levels of SNAP47 decreased independent of the activity of virus-encoded proteinase 3C. We further demonstrated that the depletion of SNAP47 inhibited CVB3 infection, indicating a pro-viral function of SNAP47. Moreover, we found that SNAP47 co-localizes with the autophagy-related protein ATG14 on the cellular membrane fractions together with viral capsid protein VP1, and expression of SNAP47 or ATG14 enhanced VP1 conjugation. Finally, we revealed that disulfide interactions had an important role in strengthening VP1 conjugation. Collectively, our study elucidated a mechanism by which SNAP47 and ATG14 promoted CVB3 propagation through facilitating viral capsid assembly. Full article
(This article belongs to the Collection Role of Autophagy in Viral Infection)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-328
Previous Issue
Next Issue
Back to TopTop