Cells

18 pages, 2336 KiB

Open AccessArticle

The Alteration of Circulating Invariant Natural Killer T, γδT, and Natural Killer Cells after Ischemic Stroke in Relation to Clinical Outcomes: A Prospective Case–Control Study

by Magdalena Frydrychowicz, Magdalena Telec, Jacek Anioła, Radosław Kazmierski, Hanna Chowaniec, Grzegorz Dworacki, Izabela Wojtasz, Wojciech Kozubski and Maria Łukasik

Cells 2024, 13(16), 1401; https://doi.org/10.3390/cells13161401 - 22 Aug 2024

Viewed by 739

Abstract

The adaptive response occurs only after 7–10 days of antigen presentation. Nevertheless, the autoreactive T cells infiltrate the stroke lesion within the first 48 h. Thus, we hypothesized that the unconventional lymphocytes as invariant natural killer T cells (iNKT) and γδT cells that [...] Read more.

The adaptive response occurs only after 7–10 days of antigen presentation. Nevertheless, the autoreactive T cells infiltrate the stroke lesion within the first 48 h. Thus, we hypothesized that the unconventional lymphocytes as invariant natural killer T cells (iNKT) and γδT cells that share immediate innate and delayed adaptive response features are involved in acute stroke pathophysiology. We assessed prospectively the quantity of circulating iNKT cells, γδT cells, and NK cells with flow cytometry in 52 subjects within three months after stroke, and we compared the results with those obtained in age-, sex-, and vascular risk factor-matched controls. We studied lymphocyte parameters regarding clinical outcomes, infarct volume, stroke-associated infection (SAI), and burden risk factors. The reduced number of circulating γδT cells and decreased percentage of the Vδ2 subset in the acute phase of stroke correlated with worse neurological status in the recovery phase. In subjects treated with thrombolysis and those who developed SAI, a lower percentage of γδT cells in the 90-day follow-up was observed. An increased percentage of iNKT cells in the acute and subacute phases of stroke was observed, and it was related to the worse clinical status. The circulating NK cells do not change temporarily or affect the outcomes after stroke. It seems that γδT cells play a long-lasting role in ischemic stroke, mainly related to the Vδ2 subset. The role of iNKT cells appears to be detrimental, especially in the acute and subacute phases of stroke. The effect of circulating NK cells on the outcome after stroke seems negligible. Full article

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14 pages, 958 KiB

Open AccessReview

New Insights into D-Aspartate Signaling in Testicular Activity

by Sara Falvo, Alessandra Santillo, Maria Maddalena Di Fiore, Massimo Venditti, Giulia Grillo, Debora Latino, Isabella Baccari, Giuseppe Petito and Gabriella Chieffi Baccari

Cells 2024, 13(16), 1400; https://doi.org/10.3390/cells13161400 - 22 Aug 2024

Viewed by 927

Abstract

D-aspartate (D-Asp) is an amino acid found in high concentrations in the testis and pituitary gland. Increasing evidence suggests that D-Asp promotes spermatogenesis by activating testosterone production in the Leydig cells via LH release from the pituitary gland. In vitro studies indicate that [...] Read more.

D-aspartate (D-Asp) is an amino acid found in high concentrations in the testis and pituitary gland. Increasing evidence suggests that D-Asp promotes spermatogenesis by activating testosterone production in the Leydig cells via LH release from the pituitary gland. In vitro studies indicate that D-Asp may also influence steroidogenesis and spermatogenesis through autocrine and paracrine signals. D-Asp enhances StAR and steroidogenic enzyme expressions, facilitating testicular cell proliferation via the GluR/ERK1/2 pathway. Moreover, it supports spermatogenesis by enhancing the mitochondrial function in spermatocytes, aiding in the metabolic shift during meiosis. Enhanced mitochondrial function, along with improved MAM stability and reduced ER stress, has been observed in Leydig and Sertoli cells treated with D-Asp, indicating potential benefits in steroidogenesis and spermatogenesis efficiency. Conversely, D-Asp exerts a notable anti-apoptotic effect in the testis via the AMPAR/AKT pathway, potentially mediated by antioxidant enzyme modulation to mitigate testicular oxidative stress. This review lays the groundwork for future investigations into the molecules promoting spermatogenesis by stimulating endogenous testosterone biosynthesis, with D-amino acids emerging as promising candidates. Full article

(This article belongs to the Section Cell Signaling)

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15 pages, 5830 KiB

Open AccessArticle

Unexpected Expression and Function of FcεRI in Immortalized Breast Cancer Cells: A Cautionary Null Study

by Alexandria M. Ashbaugh, David O. Lyons, Carianna M. Keyser and Nicholas A. Pullen

Cells 2024, 13(16), 1399; https://doi.org/10.3390/cells13161399 - 22 Aug 2024

Viewed by 904

Abstract

The high-affinity IgE receptor, FcεRI, is typically associated with type 2 effectors such as mast cells (MC). The relatively unique expression profile of FcεRI and accumulating evidence from pre-clinical and clinical settings, such as MC interactions with tumors, have led us to study [...] Read more.

The high-affinity IgE receptor, FcεRI, is typically associated with type 2 effectors such as mast cells (MC). The relatively unique expression profile of FcεRI and accumulating evidence from pre-clinical and clinical settings, such as MC interactions with tumors, have led us to study MCs as a potential therapeutic target in breast cancer. Our work identified MCs interacting with tumor cells at primary sites using the 4T1 (BALB/c) adenocarcinoma model in vivo. However, this analysis was complicated by a surprising finding that the tumor cells intrinsically and strongly expressed FcεRI. We further studied the expression and function of FcεRI in breast cancer cells in vitro. The 4T1 cells expressed FcεRI to a level similar to mouse bone marrow-derived MC (BMMC). Additionally, two established breast cancer cultures derived from human T-47D cells, one estrogen-dependent (E3) and the other estrogen-withdrawn (EWD8), also expressed FcεRI with EWD8 cells showing the greatest abundance. Functional analyses indicated that IgE-mediated antigen stimulation did not elicit classic Ca²⁺ flux in breast cancer cells as seen in the respective species’ MCs; however, FcεRI crosslinking could stimulate IL-6 production from the T-47D derivatives. Preliminary analysis of primary breast cancer biopsy datasets using R2: Genomics Analysis and Visualization Platform was discordant with our in vivo model and in vitro observations. Indeed, FcεRI mRNA abundance declined in metastatic breast cancers compared to non-cancerous breast tissue. Altogether, we report a previously unidentified and immunologically substantive difference between breast cancer models and human primary tumors. Investigators pursuing FcεRI-relevant therapeutics in this context should be aware of this translational barrier. Full article

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21 pages, 1064 KiB

Open AccessReview

IL-22 in Atopic Dermatitis

by Julia Laska, Maciej Tota, Julia Łacwik, Łukasz Sędek and Krzysztof Gomułka

Cells 2024, 13(16), 1398; https://doi.org/10.3390/cells13161398 - 22 Aug 2024

Viewed by 1964

Abstract

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating [...] Read more.

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating the underlying mechanisms of the disease has facilitated the identification of new potential therapeutic targets and promising drug candidates. In this review, we summarize the newest data, considering multiple connections between IL-22 and AD. The presence of circulating IL-22 has been found to correlate with the severity of AD and is identified as a critical factor driving the inflammatory response associated with the condition. Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD. Full article

(This article belongs to the Special Issue Research on T Cells in Skin Inflammatory Disorders)

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15 pages, 1486 KiB

Open AccessReview

Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer

by Federica Polverino, Anna Mastrangelo and Giulia Guarguaglini

Cells 2024, 13(16), 1397; https://doi.org/10.3390/cells13161397 - 22 Aug 2024

Viewed by 1072

Abstract

The AurkA serine/threonine kinase is a key regulator of cell division controlling mitotic entry, centrosome maturation, and chromosome segregation. The microtubule-associated protein TPX2 controls spindle assembly and is the main AurkA regulator, contributing to AurkA activation, localisation, and stabilisation. Since their identification, AurkA [...] Read more.

The AurkA serine/threonine kinase is a key regulator of cell division controlling mitotic entry, centrosome maturation, and chromosome segregation. The microtubule-associated protein TPX2 controls spindle assembly and is the main AurkA regulator, contributing to AurkA activation, localisation, and stabilisation. Since their identification, AurkA and TPX2 have been described as being overexpressed in cancer, with a significant correlation with highly proliferative and aneuploid tumours. Despite the frequent occurrence of AurkA/TPX2 co-overexpression in cancer, the investigation of their involvement in tumorigenesis and cancer therapy resistance mostly arises from studies focusing only on one at the time. Here, we review the existing literature and discuss the mitotic phenotypes described under conditions of AurkA, TPX2, or AurkA/TPX2 overexpression, to build a picture that may help clarify their oncogenic potential through the induction of chromosome instability. We highlight the relevance of the AurkA/TPX2 complex as an oncogenic unit, based on which we discuss recent strategies under development that aim at disrupting the complex as a promising therapeutic perspective. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cell Division and Chromosome Segregation: What Can Go Wrong?)

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13 pages, 1054 KiB

Open AccessArticle

Impact of Neuroendocrine Differentiation (NED) on Enzalutamide and Abiraterone Efficacy in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Retrospective Analysis

by Giovanni Farinea, Mariangela Calabrese, Federica Carfì, Isabella Saporita, Stefano Poletto, Marco Donatello Delcuratolo, Fabio Turco, Marco Audisio, Francesco Rosario Di Stefano, Marcello Tucci and Consuelo Buttigliero

Cells 2024, 13(16), 1396; https://doi.org/10.3390/cells13161396 - 22 Aug 2024

Viewed by 1038

Abstract

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC [...] Read more.

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC patients treated with ARPIs. Methods: We retrospectively analyzed 327 mCRPC patient data treated with Enzalutamide or Abiraterone in the first and second or successive lines of treatment. NED was assessed using prostate biopsy samples through immunohistochemical staining. Results: NED was confirmed in 32/327 (9.8%) mCRPC patients. In the overall population, mCRPC with NED showed worse PFS (4.38 vs. 11.48 months HR 2.505 [1.71–3.68] p < 0.05), disease control rate (DCR), and PSA response. In the first line setting, mCRPC with NED demonstrated worse PFS (8.5 vs. 14.9 months HR 2.13 [1.18–3.88], p < 0.05). Similarly, in the second or successive lines, mCRPC with NED showed worse PFS (4.0 vs. 7.5 months HR 2.43 [1.45–4.05] p < 0.05), DCR, PSA response and OS (12.53 vs. 18.03 months HR 1.86 [1.12–3.10] p < 0.05). The adverse impact of NED on PFS was consistence across all subgroups; we also noted a trend of worse PFS in patients with high vs. low NED. Conclusions: In our study, mCRPC with NED treated with Enzalutamide or Abiraterone showed worse clinical outcomes. NED assessment should be considered to optimize treatment decisions in the mCRPC setting. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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14 pages, 6462 KiB

Open AccessArticle

De Novo Cancer Mutations Frequently Associate with Recurrent Chromosomal Abnormalities during Long-Term Human Pluripotent Stem Cell Culture

by Diana Al Delbany, Manjusha S. Ghosh, Nuša Krivec, Anfien Huyghebaert, Marius Regin, Mai Chi Duong, Yingnan Lei, Karen Sermon, Catharina Olsen and Claudia Spits

Cells 2024, 13(16), 1395; https://doi.org/10.3390/cells13161395 - 21 Aug 2024

Viewed by 1025

Abstract

Human pluripotent stem cells (hPSCs) are pivotal in regenerative medicine, yet their in vitro expansion often leads to genetic abnormalities, raising concerns about their safety in clinical applications. This study analyzed ten human embryonic stem cell lines across multiple passages to elucidate the [...] Read more.

Human pluripotent stem cells (hPSCs) are pivotal in regenerative medicine, yet their in vitro expansion often leads to genetic abnormalities, raising concerns about their safety in clinical applications. This study analyzed ten human embryonic stem cell lines across multiple passages to elucidate the dynamics of chromosomal abnormalities and single-nucleotide variants (SNVs) in 380 cancer-related genes. Prolonged in vitro culture resulted in 80% of the lines acquiring gains of chromosome 20q or 1q, both known for conferring an in vitro growth advantage. 70% of lines also acquired other copy number variants (CNVs) outside the recurrent set. Additionally, we detected 122 SNVs in 88 genes, with all lines acquiring at least one de novo SNV during culture. Our findings showed higher loads of both CNVs and SNVs at later passages, which were due to the cumulative acquisition of mutations over a longer time in culture, and not to an increased rate of mutagenesis over time. Importantly, we observed that SNVs and rare CNVs followed the acquisition of chromosomal gains in 1q and 20q, while most of the low-passage and genetically balanced samples were devoid of cancer-associated mutations. This suggests that recurrent chromosomal abnormalities are potential drivers for the acquisition of other mutations. Full article

(This article belongs to the Special Issue Chromosomal Instability in Health and Disease)

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Graphical abstract

10 pages, 1678 KiB

Open AccessPerspective

Targeting Cleavage of C-Terminal Fragment of Cytoskeletal Filamin A in Cancers

by Ozgur Cakici, Sashidar Bandaru, Grace Yankun Lee, Dyar Mustafa and Levent M. Akyürek

Cells 2024, 13(16), 1394; https://doi.org/10.3390/cells13161394 - 21 Aug 2024

Viewed by 817

Abstract

Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted by two hinge regions between repeats 15–16 and 23–24. Cleavage of [...] Read more.

Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted by two hinge regions between repeats 15–16 and 23–24. Cleavage of these hinge regions produces a naturally occurring C-terminal 90 kDa fragment of FLNA (FLNA^CT) that physically interacts with multiple proteins with diverse functions. This cleavage leads to actin cytoskeleton remodeling, which in turn contributes to cellular signaling, nucleocytoplasmic shuttling of transcriptional factors and nuclear receptors, and regulation of their transcriptional activities that are important for initiation and progression of cancers. Therefore, recent studies have proposed blocking FLNA cleavage as a means of cancer therapy. Here, we update how FLNA cleavage has been targeted by different approaches and their potential implications for future treatment of human cancers. Full article

(This article belongs to the Special Issue Cytoskeletal Remodeling in Health and Disease)

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21 pages, 2956 KiB

Open AccessArticle

Ageing-Related Changes to H3K4me3, H3K27ac, and H3K27me3 in Purified Mouse Neurons

by Brandon Signal, Andrew J. Phipps, Katherine A. Giles, Shannon N. Huskins, Timothy R. Mercer, Mark D. Robinson, Adele Woodhouse and Phillippa C. Taberlay

Cells 2024, 13(16), 1393; https://doi.org/10.3390/cells13161393 - 21 Aug 2024

Viewed by 1864

Abstract

Neurons are central to lifelong learning and memory, but ageing disrupts their morphology and function, leading to cognitive decline. Although epigenetic mechanisms are known to play crucial roles in learning and memory, neuron-specific genome-wide epigenetic maps into old age remain scarce, often being [...] Read more.

Neurons are central to lifelong learning and memory, but ageing disrupts their morphology and function, leading to cognitive decline. Although epigenetic mechanisms are known to play crucial roles in learning and memory, neuron-specific genome-wide epigenetic maps into old age remain scarce, often being limited to whole-brain homogenates and confounded by glial cells. Here, we mapped H3K4me3, H3K27ac, and H3K27me3 in mouse neurons across their lifespan. This revealed stable H3K4me3 and global losses of H3K27ac and H3K27me3 into old age. We observed patterns of synaptic function gene deactivation, regulated through the loss of the active mark H3K27ac, but not H3K4me3. Alongside this, embryonic development loci lost repressive H3K27me3 in old age. This suggests a loss of a highly refined neuronal cellular identity linked to global chromatin reconfiguration. Collectively, these findings indicate a key role for epigenetic regulation in neurons that is inextricably linked with ageing. Full article

(This article belongs to the Section Cellular Aging)

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15 pages, 645 KiB

Open AccessReview

Common Driver Mutations in AML: Biological Impact, Clinical Considerations, and Treatment Strategies

by Tiffany Nong, Shefali Mehra and Justin Taylor

Cells 2024, 13(16), 1392; https://doi.org/10.3390/cells13161392 - 21 Aug 2024

Viewed by 1675

Abstract

Next-generation sequencing of samples from patients with acute myeloid leukemia (AML) has revealed several driver gene mutations in adult AML. However, unlike other cancers, AML is defined by relatively few mutations per patient, with a median of 4–5 depending on subtype. In this [...] Read more.

Next-generation sequencing of samples from patients with acute myeloid leukemia (AML) has revealed several driver gene mutations in adult AML. However, unlike other cancers, AML is defined by relatively few mutations per patient, with a median of 4–5 depending on subtype. In this review, we will discuss the most common driver genes found in patients with AML and focus on the most clinically relevant ones that impact treatment strategies. The most common driver gene mutations in AML occur in NPM1 and FLT3, accounting for ~30% each. There are now targeted therapies being tested or already approved for these driver genes. Menin inhibitors, a novel targeted therapy that blocks the function of the menin protein, are in clinical trials for NPM1 driver gene mutant AML after relapse. A number of FLT3 inhibitors are now approved for FLT3 driver gene mutant AML in combination with chemotherapy in the frontline and also as single agent in relapse. Although mutations in IDH1/2 and TP53 only occur in around 10–20% of patients with AML each, they can affect the treatment strategy due to their association with prognosis and availability of targeted agents. While the impact of other driver gene mutations in AML is recognized, there is a lack of data on the actionable impact of those mutations. Full article

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17 pages, 2384 KiB

Open AccessArticle

Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer

by Soraia Lobo-Martins, Patrícia Corredeira, Ana Cavaco, Carolina Rodrigues, Paulina Piairo, Cláudia Lopes, Joana Fraga, Madalena Silva, Patrícia Alves, Lisiana Wachholz Szeneszi, Ana Barradas, Camila Castro Duran, Marília Antunes, Gonçalo Nogueira-Costa, Rita Sousa, Conceição Pinto, Leonor Ribeiro, Catarina Abreu, Sofia Torres, António Quintela, Gadea Mata, Diego Megías, Julie Ribot, Karine Serre, Sandra Casimiro, Bruno Silva-Santos, Lorena Diéguez and Luís Costa Show full author list Hide full author list

Cells 2024, 13(16), 1391; https://doi.org/10.3390/cells13161391 - 21 Aug 2024

Viewed by 1448

Abstract

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2− advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i [...] Read more.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2− advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2− mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell’s subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2− mBC. Full article

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21 pages, 5290 KiB

Open AccessArticle

Temporal Transcriptomic Profiling of the Developing Xenopus laevis Eye

by Samantha J. Hack, Juli Petereit and Kelly Ai-Sun Tseng

Cells 2024, 13(16), 1390; https://doi.org/10.3390/cells13161390 - 21 Aug 2024

Viewed by 766

Abstract

Retinal progenitor cells (RPCs) are a multipotent and highly proliferative population that give rise to all retinal cell types during organogenesis. Defining their molecular signature is a key step towards identifying suitable approaches to treat visual impairments. Here, we performed RNA sequencing of [...] Read more.

Retinal progenitor cells (RPCs) are a multipotent and highly proliferative population that give rise to all retinal cell types during organogenesis. Defining their molecular signature is a key step towards identifying suitable approaches to treat visual impairments. Here, we performed RNA sequencing of whole eyes from Xenopus at three embryonic stages and used differential expression analysis to define the transcriptomic profiles of optic tissues containing proliferating and differentiating RPCs during retinogenesis. Gene Ontology and KEGG pathway analyses showed that genes associated with developmental pathways (including Wnt and Hedgehog signaling) were upregulated during the period of active RPC proliferation in early retinal development (Nieuwkoop Faber st. 24 and 27). Developing eyes had dynamic expression profiles and shifted to enrichment for metabolic processes and phototransduction during RPC progeny specification and differentiation (st. 35). Furthermore, conserved adult eye regeneration genes were also expressed during early retinal development, including sox2, pax6, nrl, and Notch signaling components. The eye transcriptomic profiles presented here span RPC proliferation to retinogenesis and include regrowth-competent stages. Thus, our dataset provides a rich resource to uncover molecular regulators of RPC activity and will allow future studies to address regulators of RPC proliferation during eye repair and regrowth. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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29 pages, 2184 KiB

Open AccessSystematic Review

Anti-Allergic and Anti-Inflammatory Signaling Mechanisms of Natural Compounds/Extracts in In Vitro System of RBL-2H3 Cell: A Systematic Review

by Tekan S. Rana, Rishipal R. Bansode and Leonard L. Williams

Cells 2024, 13(16), 1389; https://doi.org/10.3390/cells13161389 - 21 Aug 2024

Viewed by 1232

Abstract

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling [...] Read more.

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway. Full article

(This article belongs to the Section Cell Signaling)

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13 pages, 290 KiB

Open AccessEditorial

The Role of Astrocytes in CNS Disorders: Historic and Contemporary Views

by Michael Brenner and Vladimir Parpura

Cells 2024, 13(16), 1388; https://doi.org/10.3390/cells13161388 - 20 Aug 2024

Viewed by 892

Abstract

This Special Issue of Cells presents a collection of 22 published, peer-reviewed articles on the theme of “Astrocytes in CNS Disorders,” including 9 reviews of the evidence implicating astrocytes in the etiology of specific disorders, and 13 original research papers providing such evidence [...] Read more.

This Special Issue of Cells presents a collection of 22 published, peer-reviewed articles on the theme of “Astrocytes in CNS Disorders,” including 9 reviews of the evidence implicating astrocytes in the etiology of specific disorders, and 13 original research papers providing such evidence [...] Full article

(This article belongs to the Special Issue Astrocytes in CNS Disorders)

17 pages, 8251 KiB

Open AccessArticle

Cell-Specific Effects of Insulin in a Murine Model of Restenosis Under Insulin-Sensitive and Insulin-Resistant Conditions

by Marel Gonzalez Medina, Zhiwei Liu, Johny Wang, Cindy Zhang, Sarah B. Cash, Carolyn L. Cummins and Adria Giacca

Cells 2024, 13(16), 1387; https://doi.org/10.3390/cells13161387 - 20 Aug 2024

Viewed by 763

Abstract

Restenosis following percutaneous revascularization is a major challenge in patients with insulin resistance and diabetes. Currently, the vascular effects of insulin are not fully understood. In vitro, insulin’s effects on endothelial cells (ECs) are beneficial, whereas on vascular smooth muscle cells (SMCs), they [...] Read more.

Restenosis following percutaneous revascularization is a major challenge in patients with insulin resistance and diabetes. Currently, the vascular effects of insulin are not fully understood. In vitro, insulin’s effects on endothelial cells (ECs) are beneficial, whereas on vascular smooth muscle cells (SMCs), they are mitogenic. We previously demonstrated a suppressive effect of insulin on neointimal growth under insulin-sensitive conditions that was abolished in insulin-resistant conditions. Here, we aimed to determine the cell-specific effects of insulin on neointimal growth in a model of restenosis under insulin-sensitive and insulin-resistant conditions. Vascular cell-specific insulin receptor (IR)-deficient mice were fed a low-fat diet (LFD) or a high-fat, high-sucrose diet (HFSD) and implanted with an insulin pellet or vehicle prior to femoral artery wire injury. In insulin-sensitive conditions, insulin decreased neointimal growth only in controls. However, under insulin-resistant conditions, insulin had no effect in either control, EC-specific or SMC-specific IR-deficient mice. These data demonstrate that EC and SMC IRs are required for the anti-restenotic effect of insulin in insulin-sensitive conditions and that, in insulin resistance, insulin has no adverse effect on vascular SMCs in vivo. Full article

(This article belongs to the Special Issue Updates on the Mechanisms and Therapies of Cardiometabolic Disease)

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13 pages, 3324 KiB

Open AccessArticle

Effect of Culture Temperature on 2-Methylisoborneol Production and Gene Expression in Two Strains of Pseudanabaena sp.

by Rumi Park, Mi-Na Yu, Ji-Hyun Park, Taegu Kang and Jung-Eun Lee

Cells 2024, 13(16), 1386; https://doi.org/10.3390/cells13161386 - 20 Aug 2024

Viewed by 614

Abstract

The presence of the odorant 2-methylisoborneol (2-MIB) in drinking water sources is undesirable. Although 2-MIB production is known to be influenced by temperature, its regulation at the gene level and its relationship with Chlorophyll-a (Chl-a) at different temperatures remain unclear. [...] Read more.

The presence of the odorant 2-methylisoborneol (2-MIB) in drinking water sources is undesirable. Although 2-MIB production is known to be influenced by temperature, its regulation at the gene level and its relationship with Chlorophyll-a (Chl-a) at different temperatures remain unclear. This study investigates the impact of temperature on 2-MIB production and related gene expression in Pseudanabaena strains PD34 and PD35 isolated from Lake Paldang, South Korea. The strains were cultured at three temperatures (15, 25, and 30 °C) to examine cell growth, 2-MIB production, and mic gene expression levels. 2-MIB production per cell increased with higher temperatures, whereas mic gene expression levels were higher at lower temperatures, indicating a complex regulatory mechanism involving post-transcriptional and enzyme kinetics factors. Additionally, the relationship between Chl-a and 2-MIB involved in metabolic competition was analyzed, suggesting that high temperatures appear to favor 2-MIB synthesis more than Chl-a synthesis. The distinct difference in the total amount of the two products and the proportion of 2-MIB between the two strains partially explains the variations in 2-MIB production. These findings highlight the significant effect of temperature on 2-MIB biosynthesis in Pseudanabaena and provide a valuable background for gene data-based approaches to manage issues regarding 2-MIB in aquatic environments. Full article

(This article belongs to the Section Plant, Algae and Fungi Cell Biology)

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20 pages, 20118 KiB

Open AccessArticle

Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction

by João Carlos Canossa Ferreira, M. Sameiro T. Gonçalves, Ana Preto and Maria João Sousa

Cells 2024, 13(16), 1385; https://doi.org/10.3390/cells13161385 - 20 Aug 2024

Viewed by 872

Abstract

Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical [...] Read more.

Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical problem that requires further research efforts. Lysosomes play an important role in cancer cells’ survival, and targeting lysosomes has gained increased interest. In recent years, our team has been synthetizing and testing novel benzo[a]phenoxazine derivatives, as they have been shown to possess potent pharmacological activities. Here, we investigated the anticancer activity of three of the most potent derivatives from our library, C9, A36, and A42, on colorectal- and breast-cancer-derived cell lines, and compared this with the effect on non-neoplastic cell lines. We observed that the three compounds were selective for the cancer cells, namely the RKO colorectal cancer cell line and the MCF7 breast cancer cell line. In both models, the compounds reduced cell proliferation, cell survival, and cell migration, accumulated on the lysosome, and induced cell death accompanied by lysosomal membrane permeabilization (LMP), increasing the intracellular pH and ROS accumulation. Our results demonstrated that these compounds specifically target lysosomes from cancer cells, making them promising candidates as LMP inducers for cancer therapy. Full article

(This article belongs to the Section Cell Signaling)

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19 pages, 506 KiB

Open AccessReview

Autologous Fat Grafting—A Panacea for Scar Tissue Therapy?

by Nura Ahmad, Alexandra Anker, Silvan Klein, Jillian Dean, Leonard Knoedler, Katya Remy, Andrea Pagani, Sally Kempa, Amraj Terhaag and Lukas Prantl

Cells 2024, 13(16), 1384; https://doi.org/10.3390/cells13161384 - 20 Aug 2024

Viewed by 1074

Abstract

Scars may represent more than a cosmetic concern for patients; they may impose functional limitations and are frequently associated with the sensation of itching or pain, thus impacting both psychological and physical well-being. From an aesthetic perspective, scars display variances in color, thickness, [...] Read more.

Scars may represent more than a cosmetic concern for patients; they may impose functional limitations and are frequently associated with the sensation of itching or pain, thus impacting both psychological and physical well-being. From an aesthetic perspective, scars display variances in color, thickness, texture, contour, and their homogeneity, while the functional aspect encompasses considerations of functionality, pliability, and sensory perception. Scars located in critical anatomic areas have the potential to induce profound impairments, including contracture-related mobility restrictions, thereby significantly impacting daily functioning and the quality of life. Conventional approaches to scar management may suffice to a certain extent, yet there are cases where tailored interventions are warranted. Autologous fat grafting emerges as a promising therapeutic avenue in such instances. Fundamental mechanisms underlying scar formation include chronic inflammation, fibrogenesis and dysregulated wound healing, among other contributing factors. These mechanisms can potentially be alleviated through the application of adipose-derived stem cells, which represent the principal cellular component utilized in the process of lipofilling. Adipose-derived stem cells possess the capacity to secrete proangiogenic factors such as fibroblast growth factor, vascular endothelial growth factor and hepatocyte growth factor, as well as neurotrophic factors, such as brain-derived neurotrophic factors. Moreover, they exhibit multipotency, remodel the extracellular matrix, act in a paracrine manner, and exert immunomodulatory effects through cytokine secretion. These molecular processes contribute to neoangiogenesis, the alleviation of chronic inflammation, and the promotion of a conducive milieu for wound healing. Beyond the obvious benefit in restoring volume, the adipose-derived stem cells and their regenerative capacities facilitate a reduction in pain, pruritus, and fibrosis. This review elucidates the regenerative potential of autologous fat grafting and its beneficial and promising effects on both functional and aesthetic outcomes when applied to scar tissue. Full article

(This article belongs to the Special Issue Multifaceted Roles of Mesenchymal Stem Cells in Health and Disease)

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30 pages, 3824 KiB

Open AccessReview

Molecular Susceptibility and Treatment Challenges in Melanoma

by Kiran Kumar Kolathur, Radhakanta Nag, Prathvi V Shenoy, Yagya Malik, Sai Manasa Varanasi, Ramcharan Singh Angom and Debabrata Mukhopadhyay

Cells 2024, 13(16), 1383; https://doi.org/10.3390/cells13161383 - 20 Aug 2024

Viewed by 1337

Abstract

Melanoma is the most aggressive subtype of cancer, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying [...] Read more.

Melanoma is the most aggressive subtype of cancer, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying melanoma development and progression. This review aims to offer an overview of melanoma biology, covering its transition from primary to malignant melanoma, as well as the key genes and pathways involved in the initiation and progression of this disease. Utilizing online databases, we extensively explored the general expression profile of genes, identified the most frequently altered genes and gene mutations, and examined genetic alterations responsible for drug resistance. Additionally, we studied the mechanisms responsible for immune checkpoint inhibitor resistance in melanoma. Full article

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20 pages, 4298 KiB

Open AccessArticle

Centrosomal Protein 55 Regulates Chromosomal Instability in Cancer Cells by Controlling Microtubule Dynamics

by Stefanie Muhs, Themistoklis Paraschiakos, Paula Schäfer, Simon A. Joosse and Sabine Windhorst

Cells 2024, 13(16), 1382; https://doi.org/10.3390/cells13161382 - 20 Aug 2024

Cited by 1 | Viewed by 953

Abstract

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN [...] Read more.

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics. Full article

(This article belongs to the Section Cell Microenvironment)

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Graphical abstract

19 pages, 4269 KiB

Open AccessArticle

Visual Evidence for the Recruitment of Four Enzymes with RNase Activity to the Bacillus subtilis Replication Forks

by Rebecca Hinrichs and Peter L. Graumann

Cells 2024, 13(16), 1381; https://doi.org/10.3390/cells13161381 - 20 Aug 2024

Viewed by 785

Abstract

Removal of RNA/DNA hybrids for the maturation of Okazaki fragments on the lagging strand, or due to misincorporation of ribonucleotides by DNA polymerases, is essential for all types of cells. In prokaryotic cells such as Escherichia coli, DNA polymerase 1 and RNase [...] Read more.

Removal of RNA/DNA hybrids for the maturation of Okazaki fragments on the lagging strand, or due to misincorporation of ribonucleotides by DNA polymerases, is essential for all types of cells. In prokaryotic cells such as Escherichia coli, DNA polymerase 1 and RNase HI are supposed to remove RNA from Okazaki fragments, but many bacteria lack HI-type RNases, such as Bacillus subtilis. Previous work has demonstrated in vitro that four proteins are able to remove RNA from RNA/DNA hybrids, but their actual contribution to DNA replication is unclear. We have studied the dynamics of DNA polymerase A (similar to Pol 1), 5′->3′ exonuclease ExoR, and the two endoribonucleases RNase HII and HIII in B. subtilis using single-molecule tracking. We found that all four enzymes show a localization pattern similar to that of replicative DNA helicase. By scoring the distance of tracks to replication forks, we found that all four enzymes are enriched at DNA replication centers. After inducing UV damage, RNase HIII was even more strongly recruited to the replication forks, and PolA showed a more static behavior, indicative of longer binding events, whereas RNase HII and ExoR showed no response. Inhibition of replication by 6(p hydroxyphenylazo)-uracil (HPUra) demonstrated that both RNase HII and RNase HIII are directly involved in the replication. We found that the absence of ExoR increases the likelihood of RNase HIII at the forks, indicating that substrate availability rather than direct protein interactions may be a major driver for the recruitment of RNases to the lagging strands. Thus, B. subtilis replication forks appear to be an intermediate between E. coli type and eukaryotic replication forks and employ a multitude of RNases, rather than any dedicated enzyme for RNA/DNA hybrid removal. Full article

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Graphical abstract

12 pages, 734 KiB

Open AccessReview

The Impact of Maternal Nanoplastic and Microplastic Particle Exposure on Mammal’s Offspring

by Hong-Ren Yu, Jiunn-Ming Sheen and Mao-Meng Tiao

Cells 2024, 13(16), 1380; https://doi.org/10.3390/cells13161380 - 20 Aug 2024

Viewed by 1435

Abstract

The issue of environmental nanoplastic (NPl) particle and microplastic (MPl) particle pollution is becoming increasingly severe, significantly impacting ecosystems and biological health. Research shows that NPl/MPl can penetrate the placental barrier and enter the fetus, leading to transgenerational effects. This review integrates the [...] Read more.

The issue of environmental nanoplastic (NPl) particle and microplastic (MPl) particle pollution is becoming increasingly severe, significantly impacting ecosystems and biological health. Research shows that NPl/MPl can penetrate the placental barrier and enter the fetus, leading to transgenerational effects. This review integrates the existing literature on the effects of prenatal NPl/MPl exposure on mammalian offspring, focusing particularly on its negative impacts on the central nervous system, liver, intestinal health, reproductive function, and skeletal muscles. The vast majority of previous studies on prenatal NPl/MPl in mammals have used polystyrene material. Future research should explore the effects of other prenatal NPl/MPl materials on offspring to better reflect the realities of the human environment. It is also essential to investigate the potential harm and underlying mechanisms associated with prenatal NPl/MPl exposure to offspring in greater depth. This will aid in developing appropriate prevention and treatment strategies in the future. Full article

(This article belongs to the Special Issue Environmental Exposure and Cell Damage)

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15 pages, 4960 KiB

Open AccessTechnical Note

In Vivo Tracking and 3D Mapping of Cell Death in Regeneration and Cancer Using Trypan Blue

by Nicole Procel, Karen Camacho, Elisabeth Verboven, Isabel Baroja, Priscila A. Guerrero, Hanne Hillen, Carlos Estrella-García, Nicole Vizcaíno-Rodríguez, Leticia Sansores-Garcia, Ana Santamaría-Naranjo, Andrés Romero-Carvajal, Andrés Caicedo, Georg Halder and Iván M. Moya

Cells 2024, 13(16), 1379; https://doi.org/10.3390/cells13161379 - 20 Aug 2024

Viewed by 1449

Abstract

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. [...] Read more.

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl₄ intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo “pulse and chase” tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease. Full article

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27 pages, 4780 KiB

Open AccessReview

Mononuclear Phagocytes, Cellular Immunity, and Nobel Prizes: A Historic Perspective

by Siamon Gordon, Annabell Roberti and Stefan H. E. Kaufmann

Cells 2024, 13(16), 1378; https://doi.org/10.3390/cells13161378 - 19 Aug 2024

Viewed by 1614

Abstract

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with [...] Read more.

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity. Full article

(This article belongs to the Special Issue In Honor of Nobel Prize in Physiology or Medicine: Cell-Mediated Immunity)

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25 pages, 7783 KiB

Open AccessArticle

Tomato Spotted Wilt Virus Suppresses the Antiviral Response of the Insect Vector, Frankliniella occidentalis, by Elevating an Immunosuppressive C18 Oxylipin Level Using Its Virulent Factor, NSs

by Niayesh Shahmohammadi, Falguni Khan, Gahyeon Jin, Minji Kwon, Donghee Lee and Yonggyun Kim

Cells 2024, 13(16), 1377; https://doi.org/10.3390/cells13161377 - 19 Aug 2024

Viewed by 817

Abstract

Orthotospovirus tomatomaculae (tomato spotted wilt virus, TSWV) is transmitted by the western flower thrips, Frankliniella occidentalis. Epoxyoctadecamonoenoic acids (EpOMEs) function as immune-suppressive factors, particularly in insects infected by viral pathogens. These oxylipins are produced by cytochrome P450 monooxygenases (CYPs) and are degraded [...] Read more.

Orthotospovirus tomatomaculae (tomato spotted wilt virus, TSWV) is transmitted by the western flower thrips, Frankliniella occidentalis. Epoxyoctadecamonoenoic acids (EpOMEs) function as immune-suppressive factors, particularly in insects infected by viral pathogens. These oxylipins are produced by cytochrome P450 monooxygenases (CYPs) and are degraded by soluble epoxide hydrolase (sEH). In this study, we tested the hypothesis that TSWV modulates the EpOME level in the thrips to suppress antiviral responses and enhance its replication. TSWV infection significantly elevated both 9,10-EpOME and 12,13-EpOME levels. Following TSWV infection, the larvae displayed apoptosis in the midgut along with the upregulated expression of four caspase genes. However, the addition of EpOME to the viral treatment notably reduced apoptosis and downregulated caspase gene expressions, which led to a marked increase in TSWV titers. The CYP and sEH genes of F. occidentalis were identified, and their expression manipulation using RNA interference (RNAi) treatments led to significant alternations in the insect’s immune responses and TSWV viral titers. To ascertain which viral factor influences the host EpOME levels, specialized RNAi treatments targeting genes encoded by TSWV were administered to larvae infected with TSWV. These treatments demonstrated that NS_S expression is pivotal in manipulating the genes involved in EpOME metabolism. These results indicate that NSs of TSWV are crucially linked with the elevation of host insect EpOME levels and play a key role in suppressing the antiviral responses of F. occidentalis. Full article

(This article belongs to the Special Issue Plant, Algae and Fungi Cell Biology: State-of-the-Art and Perspectives)

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21 pages, 1980 KiB

Open AccessReview

Iron Dyshomeostasis in Neurodegeneration with Brain Iron Accumulation (NBIA): Is It the Cause or the Effect?

by Francesco Agostini, Bibiana Sgalletta and Marco Bisaglia

Cells 2024, 13(16), 1376; https://doi.org/10.3390/cells13161376 - 19 Aug 2024

Cited by 1 | Viewed by 1097

Abstract

Iron is an essential metal ion implicated in several cellular processes. However, the reactive nature of iron renders this metal ion potentially dangerous for cells, and its levels need to be tightly controlled. Alterations in the intracellular concentration of iron are associated with [...] Read more.

Iron is an essential metal ion implicated in several cellular processes. However, the reactive nature of iron renders this metal ion potentially dangerous for cells, and its levels need to be tightly controlled. Alterations in the intracellular concentration of iron are associated with different neuropathological conditions, including neurodegeneration with brain iron accumulation (NBIA). As the name suggests, NBIA encompasses a class of rare and still poorly investigated neurodegenerative disorders characterized by an abnormal accumulation of iron in the brain. NBIA is mostly a genetic pathology, and to date, 10 genes have been linked to familial forms of NBIA. In the present review, after the description of the principal mechanisms implicated in iron homeostasis, we summarize the research data concerning the pathological mechanisms underlying the genetic forms of NBIA and discuss the potential involvement of iron in such processes. The picture that emerges is that, while iron overload can contribute to the pathogenesis of NBIA, it does not seem to be the causal factor in most forms of the pathology. The onset of these pathologies is rather caused by a combination of processes involving the interplay between lipid metabolism, mitochondrial functions, and autophagic activity, eventually leading to iron dyshomeostasis. Full article

(This article belongs to the Collection Molecular Insights into Neurodegenerative Diseases)

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1 pages, 150 KiB

Open AccessCorrection

Correction: Odegaard et al. Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure. Cells 2022, 11, 1740

by Katherine E. Odegaard, Gabriel Gallegos, Sneh Koul, Victoria L. Schaal, Neetha N. Vellichirammal, Chittibabu Guda, Andrea P. Dutoit, Steven J. Lisco, Sowmya V. Yelamanchili and Gurudutt Pendyala

Cells 2024, 13(16), 1375; https://doi.org/10.3390/cells13161375 - 19 Aug 2024

Viewed by 438

Abstract

In the original publication [...] Full article

2 pages, 1794 KiB

Open AccessCorrection

Correction: Raha et al. Lipid-Lowering Drug Gemfibrozil Protects Mice from Tay-Sachs Disease via Peroxisome Proliferator-Activated Receptor α. Cells 2023, 12, 2791

by Sumita Raha, Debashis Dutta, Ramesh K. Paidi and Kalipada Pahan

Cells 2024, 13(16), 1374; https://doi.org/10.3390/cells13161374 - 19 Aug 2024

Viewed by 433

Abstract

Error in Figure 4 [...] Full article

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12 pages, 4651 KiB

Open AccessArticle

Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes

by Hiroshi Yamada, Hirona Osaka, Nanami Tatsumi, Miu Araki, Tadashi Abe, Keiko Kaihara, Ken Takahashi, Eizo Takashima, Takayuki Uchihashi, Keiji Naruse and Kohji Takei

Cells 2024, 13(16), 1373; https://doi.org/10.3390/cells13161373 - 17 Aug 2024

Viewed by 1064

Abstract

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in [...] Read more.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with α-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of α-actinin and enhanced the α-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to α-actinin via its globular ends. The interaction between α-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with α-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. Full article

(This article belongs to the Special Issue Muscle Structure and Function in Health and Disease)

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17 pages, 4127 KiB

Open AccessArticle

Impact of the Immunomodulatory Factor Soluble B7-H4 in the Progress of Preeclampsia by Inhibiting Essential Functions of Extravillous Trophoblast Cells

by Yuyang Ma, Liyan Duan, Beatrix Reisch, Rainer Kimmig, Antonella Iannaccone and Alexandra Gellhaus

Cells 2024, 13(16), 1372; https://doi.org/10.3390/cells13161372 - 17 Aug 2024

Cited by 1 | Viewed by 955

Abstract

A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of [...] Read more.

A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of processes, including T-cell activation, cytokine release, and tumour progression. Our previous findings indicated that B7-H4 levels are elevated in both maternal blood and placental villous tissue during the early stages of preeclampsia. Here, we investigated the function of B7-H4 in trophoblast physiology. Recombinant B7-H4 protein was used to treat human SGHPL-5 extravillous trophoblast cells. Biological functions were investigated using MTT, wound healing, and transwell assays. Signalling pathways were analysed by immunoblotting and immunofluorescence. The functionality of B7-H4 was further confirmed by immunoblotting and immunohistochemical analysis in placental tissues from control and preeclamptic patients following therapeutic plasma exchange (TPE) or standard of care treatment. This study showed that B7-H4 inhibited the proliferation, migration, and invasion capacities of SGHPL-5 extravillous cells while promoting apoptosis by downregulating the PI3K/Akt/STAT3 signalling pathway. These results were consistently confirmed in placental tissues from preterm controls compared to early-onset preeclamptic placental tissues from patients treated with standard of care or TPE treatment. B7-H4 may play a role in the development of preeclampsia by inhibiting essential functions of extravillous trophoblast cells during placental development. One possible mechanism by which TPE improves pregnancy outcomes in preeclampsia is through the elimination of B7-H4 amongst other factors. Full article

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Cells, Volume 13, Issue 16 (August-2 2024) – 93 articles

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