Journal Description
Cells
Cells
is an international, peer-reviewed, open access journal of cell biology, molecular biology, and biophysics, published semimonthly online by MDPI. The Spanish Society for Biochemistry and Molecular Biology (SEBBM), Signal Transduction Society (STS), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH) and Society for Regenerative Medicine (Russian Federation) (RPO) are affiliated with Cells and their members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Cell Biology) / CiteScore - Q1 (General Biochemistry, Genetics and Molecular Biology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 15.7 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2022).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 20 topical sections.
- Companion journal: Organoids.
Impact Factor:
7.666 (2021)
;
5-Year Impact Factor:
7.677 (2021)
Latest Articles
The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved
Cells 2022, 11(15), 2465; https://doi.org/10.3390/cells11152465 (registering DOI) - 08 Aug 2022
Abstract
Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory
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Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis identified more than 3000 proteins in human islets. Cytokines alone altered the expression of 244 proteins (145 up- and 99 down-regulated), while, in the presence of metformin, cytokine-exposure modified the expression of 231 proteins (128 up- and 103 downregulated). Among the proteins inversely regulated in the two conditions, we found proteins involved in vesicle motility, defense against oxidative stress (including peroxiredoxins), metabolism, protein synthesis, glycolysis and its regulation, and cytoskeletal proteins. Metformin inhibited pathways linked to inflammation, immune reactions, mammalian target of rapamycin (mTOR) signaling, and cell senescence. Some of the changes were confirmed by Western blot. Therefore, metformin prevented part of the deleterious actions of pro-inflammatory cytokines in human β-cells, which was accompanied by islet proteome modifications. This suggests that metformin, besides use in T2D, might be considered for β-cell protection in other types of diabetes, possibly including early T1D.
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Open AccessReview
Efp/TRIM25 and Its Related Protein, TRIM47, in Hormone-Dependent Cancers
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and
Cells 2022, 11(15), 2464; https://doi.org/10.3390/cells11152464 (registering DOI) - 08 Aug 2022
Abstract
Increasing attention has been paid to the biological roles of tripartite motif-containing (TRIM) family proteins, which typically function as E3 ubiquitin ligases. Estrogen-responsive finger protein (Efp), a member of the TRIM family proteins, also known as TRIM25, was originally identified as a protein
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Increasing attention has been paid to the biological roles of tripartite motif-containing (TRIM) family proteins, which typically function as E3 ubiquitin ligases. Estrogen-responsive finger protein (Efp), a member of the TRIM family proteins, also known as TRIM25, was originally identified as a protein induced by estrogen and plays critical roles in promoting endocrine-related cancers, including breast cancer, endometrial cancer, and prostate cancer. The pathophysiological importance of Efp made us interested in the roles of other TRIM family proteins that share a similar structure with Efp. Based on a phylogenetic analysis of the C-terminal region of TRIM family proteins, we focused on TRIM47 as a protein belonging to the same branch as Efp. TRIM47 is a poor prognostic factor in both breast cancer and prostate cancer. Atypical lysine-27-like poly-ubiquitination was involved in the underlying mechanism causing endocrine resistance in breast cancer. We also discuss the functions of Efp and TRIM47 in other types of cancers and innate immunity by introducing substrates the are modified by poly-ubiquitination.
Full article
(This article belongs to the Special Issue Mechanism of Nuclear Hormone Receptors in Cancer)
Open AccessEditorial
Ll-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis
by
and
Cells 2022, 11(15), 2463; https://doi.org/10.3390/cells11152463 (registering DOI) - 08 Aug 2022
Abstract
Innate immunity responds to infections and inflammatory stimuli through a carefully choreographed set of interactions between cells, stimuli and their specific receptors. Of particular importance are endogenous peptides, which assume roles as defensins or alarmins, growth factors or wound repair inducers. LL-37, a
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Innate immunity responds to infections and inflammatory stimuli through a carefully choreographed set of interactions between cells, stimuli and their specific receptors. Of particular importance are endogenous peptides, which assume roles as defensins or alarmins, growth factors or wound repair inducers. LL-37, a proteolytic fragment of cathelicidin, fulfills the roles of a defensin by inserting into the membranes of bacterial pathogens, functions as alarmin in stimulating chemotaxis of innate immune cells, and alters the structure and efficacy of various cytokines. Here, we draw attention to the direct effect of LL-37 on neutrophils and the release of extracellular traps (NETs), as NETs have been established as mediators of immune defense against pathogens but also as important contributors to chronic disease and tissue pathogenesis. We propose a specific structural basis for LL-37 function, in part by highlighting the structural flexibility of LL-37 and its ability to adapt to distinct microenvironments and interacting counterparts.
Full article
(This article belongs to the Special Issue NETs in Infectious and Inflammatory Diseases)
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Open AccessArticle
Assessment of a Serum Microrna Risk Score for Colorectal Cancer among Participants of Screening Colonoscopy at Various Stages of Colorectal Carcinogenesis
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, , , , and
Cells 2022, 11(15), 2462; https://doi.org/10.3390/cells11152462 (registering DOI) - 08 Aug 2022
Abstract
We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score
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We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score among participants of screening colonoscopy at various stages of colorectal carcinogenesis. MicroRNAs (miRNAs) were profiled by quantitative-real-time-polymerase-chain-reaction in the serum samples of screening colonoscopy participants with CRC (n = 52), advanced colorectal adenoma (AA, n = 100), non-advanced colorectal adenoma (NAA, n = 88), and participants free of colorectal neoplasms (n = 173). The mean values of the miR-score were compared between groups by the Mann–Whitney U test. The associations of the miR-score with risk for colorectal neoplasms were evaluated using logistic regression analyses. MicroRNA risk scores were significantly higher among participants with AA than among those with NAA (p = 0.027) and those with CRC (p = 0.014), whereas no statistically significant difference was seen between those with NAA and those with no colorectal neoplasms (p = 0.127). When comparing adjacent groups, miR-scores were inversely associated with CRC versus AA and positively associated with AA versus NAA [odds ratio (OR), 0.37 (95% confidence interval (CI), 0.16–0.86) and OR, 2.22 (95% CI, 1.06–4.64) for the top versus bottom tertiles, respectively]. Our results are consistent with the hypothesis that a high miR-score may be indicative of an increased CRC risk by an increased tendency of progression from non-advanced to advanced colorectal neoplasms, along with a change of the miR-patterns after CRC manifestation.
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(This article belongs to the Special Issue The Research of Biomarkers in Colorectal Cancer and Gastric Cancer)
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Open AccessArticle
Pharmacological Activation of Potassium Channel Kv11.1 with NS1643 Attenuates Triple Negative Breast Cancer Cell Migration by Promoting the Dephosphorylation of Caveolin-1
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, , , , , , , and
Cells 2022, 11(15), 2461; https://doi.org/10.3390/cells11152461 (registering DOI) - 08 Aug 2022
Abstract
The prevention of metastasis is a central goal of cancer therapy. Caveolin-1 (Cav-1) is a structural membrane and scaffolding protein shown to be a key regulator of late-stage breast cancer metastasis. However, therapeutic strategies targeting Cav-1 are still lacking. Here, we demonstrate that
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The prevention of metastasis is a central goal of cancer therapy. Caveolin-1 (Cav-1) is a structural membrane and scaffolding protein shown to be a key regulator of late-stage breast cancer metastasis. However, therapeutic strategies targeting Cav-1 are still lacking. Here, we demonstrate that the pharmacological activation of potassium channel Kv11.1, which is uniquely expressed in MDA-MB-231 triple negative breast cancer cells (TNBCs) but not in normal MCF-10A cells, induces the dephosphorylation of Cav-1 Tyr-14 by promoting the Ca2+-dependent stimulation of protein tyrosine phosphatase 1B (PTP1B). Consequently, the dephosphorylation of Cav-1 resulted in its disassociation from β-catenin, which enabled the accumulation of β-catenin at cell borders, where it facilitated the formation of cell–cell adhesion complexes via interactions with R-cadherin and desmosomal proteins. Kv11.1 activation-dependent Cav-1 dephosphorylation induced with NS1643 also reduced cell migration and invasion, consistent with its ability to regulate focal adhesion dynamics. Thus, this study sheds light on a novel pharmacological mechanism of promoting Cav-1 dephosphorylation, which may prove to be effective at reducing metastasis and promoting contact inhibition.
Full article
(This article belongs to the Collection Feature Papers in Cell Motility and Adhesion)
Open AccessArticle
Static Magnetic Fields Regulate T-Type Calcium Ion Channels and Mediate Mesenchymal Stem Cells Proliferation
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, , , , , , , , , , , , , and
Cells 2022, 11(15), 2460; https://doi.org/10.3390/cells11152460 (registering DOI) - 08 Aug 2022
Abstract
The static magnetic fields (SMFs) impact on biological systems, induce a variety of biological responses, and have been applied to the clinical treatment of diseases. However, the underlying mechanisms remain largely unclear. In this report, by using human mesenchymal stem cells (MSCs) as
[...] Read more.
The static magnetic fields (SMFs) impact on biological systems, induce a variety of biological responses, and have been applied to the clinical treatment of diseases. However, the underlying mechanisms remain largely unclear. In this report, by using human mesenchymal stem cells (MSCs) as a model, we investigated the biological effect of SMFs at a molecular and cellular level. We showed that SMF exposure promotes MSC proliferation and activates the expression of transcriptional factors such as FOS (Fos Proto-Oncogene, AP-1 Transcription Factor Subunit) and EGR1 (Early Growth Response 1). In addition, the expression of signal-transduction proteins p-ERK1/2 and p-JNK oscillate periodically with SMF exposure time. Furthermore, we found that the inhibition of the T-type calcium ion channels negates the biological effects of SMFs on MSCs. Together, we revealed that the SMFs regulate T-type calcium ion channels and mediate MSC proliferation via the MAPK signaling pathways.
Full article
(This article belongs to the Collection Magnetic Fields and Cells)
Open AccessReview
Role of Spectrin in Endocytosis
by
Cells 2022, 11(15), 2459; https://doi.org/10.3390/cells11152459 (registering DOI) - 08 Aug 2022
Abstract
Cytoskeletal spectrin is found in (non)erythroid cells. Eukaryotic endocytosis takes place for internalizing cargos from extracellular milieu. The role of spectrin in endocytosis still remains poorly understood. Here, I summarize current knowledge of spectrin function, spectrin-based cytoskeleton and endocytosis of erythrocytes, and highlight
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Cytoskeletal spectrin is found in (non)erythroid cells. Eukaryotic endocytosis takes place for internalizing cargos from extracellular milieu. The role of spectrin in endocytosis still remains poorly understood. Here, I summarize current knowledge of spectrin function, spectrin-based cytoskeleton and endocytosis of erythrocytes, and highlight how spectrin contributes to endocytosis and working models in different types of cells. From an evolutionary viewpoint, I discuss spectrin and endocytosis in a range of organisms, particularly in plants and yeast where spectrin is absent. Together, the role of spectrin in endocytosis is related to its post-translational modification, movement/rearrangement, elimination (by proteases) and meshwork fencing.
Full article
(This article belongs to the Section Organelle Function)
Open AccessReview
Endogenous Retroviruses and Placental Evolution, Development, and Diversity
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, , , , , and
Cells 2022, 11(15), 2458; https://doi.org/10.3390/cells11152458 (registering DOI) - 08 Aug 2022
Abstract
The main roles of placentas include physical protection, nutrient and oxygen import, export of gasses and fetal waste products, and endocrinological regulation. In addition to physical protection of the fetus, the placentas must provide immune protection throughout gestation. These basic functions are well-conserved;
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The main roles of placentas include physical protection, nutrient and oxygen import, export of gasses and fetal waste products, and endocrinological regulation. In addition to physical protection of the fetus, the placentas must provide immune protection throughout gestation. These basic functions are well-conserved; however, placentas are undoubtedly recent evolving organs with structural and cellular diversities. These differences have been explained for the last two decades through co-opting genes and gene control elements derived from transposable elements, including endogenous retroviruses (ERVs). However, the differences in placental structures have not been explained or characterized. This manuscript addresses the sorting of ERVs and their integration into the mammalian genomes and provides new ways to explain why placental structures have diverged.
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(This article belongs to the Special Issue Placental Development in Health and Disease)
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Open AccessArticle
Genome-Wide Association Analysis Reveals Trait-Linked Markers for Grain Nutrient and Agronomic Traits in Diverse Set of Chickpea Germplasm
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, , , , , , and
Cells 2022, 11(15), 2457; https://doi.org/10.3390/cells11152457 (registering DOI) - 08 Aug 2022
Abstract
Chickpea is an inexpensive source of protein, minerals, and vitamins to the poor people living in arid and semi-arid regions of Southern Asia and Sub-Saharan Africa. New chickpea cultivars with enhanced levels of protein, Fe and Zn content are a medium-term strategy for
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Chickpea is an inexpensive source of protein, minerals, and vitamins to the poor people living in arid and semi-arid regions of Southern Asia and Sub-Saharan Africa. New chickpea cultivars with enhanced levels of protein, Fe and Zn content are a medium-term strategy for supplying essential nutrients for human health and reducing malnutrition. In the current study, a chickpea reference set of 280 accessions, including landraces, breeding lines, and advanced cultivars, was evaluated for grain protein, Fe, Zn content and agronomic traits over two seasons. Using a mid-density 5k SNP array, 4603 highly informative SNPs distributed across the chickpea genome were used for GWAS analysis. Population structure analysis revealed three subpopulations (K = 3). Linkage disequilibrium (LD) was extensive, and LD decay was relatively low. A total of 20 and 46 marker-trait associations (MTAs) were identified for grain nutrient and agronomic traits, respectively, using FarmCPU and BLINK models. Of which seven SNPs for grain protein, twelve for Fe, and one for Zn content were distributed on chromosomes 1, 4, 6, and 7. The marker S4_4477846 on chr4 was found to be co-associated with grain protein over seasons. The markers S1_11613376 and S1_2772537 co-associated with grain Fe content under NSII and pooled seasons and S7_9379786 marker under NSI and pooled seasons. The markers S4_31996956 co-associated with grain Fe and days to maturity. SNP annotation of associated markers were found to be related to gene functions of metal ion binding, transporters, protein kinases, transcription factors, and many more functions involved in plant metabolism along with Fe and protein homeostasis. The identified significant MTAs has potential use in marker-assisted selection for developing nutrient-rich chickpea cultivars after validation in the breeding populations.
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(This article belongs to the Special Issue Omics in Plant Genetics and Breeding)
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Open AccessArticle
HSSG: Identification of Cancer Subtypes Based on Heterogeneity Score of A Single Gene
Cells 2022, 11(15), 2456; https://doi.org/10.3390/cells11152456 (registering DOI) - 08 Aug 2022
Abstract
Cancer is a highly heterogeneous disease, which leads to the fact that even the same cancer can be further classified into different subtypes according to its pathology. With the multi-omics data widely used in cancer subtypes identification, effective feature selection is essential for
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Cancer is a highly heterogeneous disease, which leads to the fact that even the same cancer can be further classified into different subtypes according to its pathology. With the multi-omics data widely used in cancer subtypes identification, effective feature selection is essential for accurately identifying cancer subtypes. However, the feature selection in the existing cancer subtypes identification methods has the problem that the most helpful features cannot be selected from a biomolecular perspective, and the relationship between the selected features cannot be reflected. To solve this problem, we propose a method for feature selection to identify cancer subtypes based on the heterogeneity score of a single gene: HSSG. In the proposed method, the sample-similarity network of a single gene is constructed, and pseudo-F statistics calculates the heterogeneity score for cancer subtypes identification of each gene. Finally, we construct gene-gene networks using genes with higher heterogeneity scores and mine essential genes from the networks. From the seven TCGA data sets for three experiments, including cancer subtypes identification in single-omics data, the performance in feature selection of multi-omics data, and the effectiveness and stability of the selected features, HSSG achieves good performance in all. This indicates that HSSG can effectively select features for subtypes identification.
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(This article belongs to the Collection Computational Imaging for Biophotonics and Biomedicine)
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Open AccessArticle
Estimating Biomass and Vitality of Microalgae for Monitoring Cultures: A Roadmap for Reliable Measurements
Cells 2022, 11(15), 2455; https://doi.org/10.3390/cells11152455 (registering DOI) - 08 Aug 2022
Abstract
Estimating algal biomass is a prerequisite for monitoring growth of microalgae. Especially for large-scale production sites, the measurements must be robust, reliable, fast and easy to obtain. We compare the relevant parameters, discuss potential hurdles and provide recommendations to tackle these issues. The
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Estimating algal biomass is a prerequisite for monitoring growth of microalgae. Especially for large-scale production sites, the measurements must be robust, reliable, fast and easy to obtain. We compare the relevant parameters, discuss potential hurdles and provide recommendations to tackle these issues. The focus is on optical density and in vivo autofluorescence of chlorophyll, which have proven to be ideal candidates for monitoring purposes. Beyond biomass, cell vitality is also crucial for maintaining cultures. While maximizing biomass yield is often the primary consideration, some applications require adverse growth conditions for the synthesis of high-quality compounds. The non-invasive technique of pulse-amplified modulated (PAM) fluorescence measurements provides an ideal tool and is increasingly being employed due to ever more affordable devices. We compared three devices and studied the robustness of the dark fluorescence yield of photosystem II (Fv/Fm) at various cell densities. Although the so-called inner filter effects influence the fluorescence signal, the resulting Fv/Fm remain stable and robust over a wide range of cell densities due to mutual effects.
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(This article belongs to the Special Issue Growth and Division in Algae)
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Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles
by
, , , , , , , and
Cells 2022, 11(15), 2454; https://doi.org/10.3390/cells11152454 (registering DOI) - 08 Aug 2022
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging
[...] Read more.
Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging as important players in serotonin uptake. We hypothesized that OCT3 and/or PMAT are functionally upregulated in juveniles, thereby buffering SSRIs’ ability to enhance serotonergic neurotransmission. Unlike in adult mice, we found the OCT/PMAT blocker, decynium-22, to have standalone antidepressant-like effects in juveniles. Using in vivo high-speed chronoamperometry, we found that juveniles clear serotonin from the CA3 region of the hippocampus ~2-fold faster than adult mice. Cell density did not differ between ages, suggesting that faster serotonin clearance in juveniles is unrelated to faster diffusion through the extracellular matrix. Western blot and immunohistochemistry showed that juvenile mice have modestly greater expression of PMAT than adults, whereas OCT3 expression in the CA3 region of the hippocampus was similar between ages. Together, these data suggest that faster serotonin clearance and antidepressant-like effects of decynium-22 in juvenile mice may be due to functionally upregulated PMAT. Faster serotonin clearance via PMAT in juveniles may contribute to reduced therapeutic efficacy of SSRIs in children relative to adults.
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(This article belongs to the Special Issue Neurotransmitter Transporters in Health and Disease)
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Open AccessArticle
Phaseolus vulgaris Erythroagglutinin (PHA-E)-Positive Ceruloplasmin Acts as a Potential Biomarker in Pancreatic Cancer Diagnosis
Cells 2022, 11(15), 2453; https://doi.org/10.3390/cells11152453 (registering DOI) - 08 Aug 2022
Abstract
Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable
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Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as CA19-9 and CEA have already been utilized in clinics. In this study, we analyzed the alteration of N-glycan of serum glycoproteins by mass spectrometry and lectin blotting. The results showed that bisecting GlcNAc structures of glycoproteins are significantly increased in PC patients’ sera. With Phaseolus vulgaris Erythroagglutinin (PHA-E) lectin that specifically recognizes bisecting GlcNAc N-glycans, the serum glycoproteins bearing bisecting GlcNAc in PC patients’ sera were pulled down and identified by nano-LC-MS/MS. Among them, ceruloplasmin (Cp) was screened out with a satisfied sensitivity and specificity in identifying PC from acute pancreatitis patients (AUC: 0.757) and normal healthy persons (AUC: 0.972), suggesting a close association between Cp and PC development and diagnosis. To prove that, the Cp expression in tumor tissues of PC patients was examined. The results showed that Cp was significantly upregulated in PC tissues compared to that in adjacent normal tissues. All these results suggested that PHA-E-positive Cp could be a potential PC-specific glycoprotein marker to distinguish PC patients from acute pancreatitis patients and normal persons.
Full article
(This article belongs to the Special Issue Glycobiology in Cancer: From Molecular Mechanisms to Therapeutic Opportunities)
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Endothelial Glycocalyx Morphology in Different Flow Regions of the Aqueous Outflow Pathway of Normal and Laser-Induced Glaucoma Monkey Eyes
Cells 2022, 11(15), 2452; https://doi.org/10.3390/cells11152452 - 07 Aug 2022
Abstract
Glycocalyx morphology was examined in the trabecular outflow pathway of monkey eyes with and without experimental glaucoma. Laser burns were administered along ~270 degrees of the trabecular meshwork (TM) of one eye (n = 6) or both eyes (n = 2)
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Glycocalyx morphology was examined in the trabecular outflow pathway of monkey eyes with and without experimental glaucoma. Laser burns were administered along ~270 degrees of the trabecular meshwork (TM) of one eye (n = 6) or both eyes (n = 2) of each monkey until intraocular pressure remained elevated. Portions of the TM were not laser-treated. Unlasered eyes (n = 6) served as controls. Enucleated eyes were perfused at 15 mmHg to measure the outflow facility, perfused with fluorescein to evaluate the outflow pattern, perfusion-fixed for glycocalyx labeling, and processed for electron microscopy. Coverage and thickness of the glycocalyx were measured in the TM, Schlemm’s canal (SC), collector channels (CCs), intrascleral veins (ISVs), and episcleral veins (ESVs) in non-lasered regions and high- and low-flow regions of controls. Compared to controls, laser-treated eyes had decreased outflow facility (p = 0.02). Glycocalyx thickness increased from the TM to ESVs in non-lasered regions and controls (p < 0.05). Glycocalyx coverage was generally greater distally in non-lasered regions (p < 0.05). In lasered regions, TM, SC, and CCs were partly to completely obliterated, and ISVs and ESVs displayed minimal glycocalyx. Whether the glycocalyx is decreased in the trabecular outflow pathway of human glaucomatous eyes warrants investigation.
Full article
(This article belongs to the Special Issue Cellular and Molecular Aspects of Tracking Endothelial Function for Clinical Diagnosis, Prognosis and Treatment)
Open AccessArticle
Three Binding Conformations of BIO124 in the Pocket of the PICK1 PDZ Domain
Cells 2022, 11(15), 2451; https://doi.org/10.3390/cells11152451 - 07 Aug 2022
Abstract
The PDZ family has drawn attention as possible drug targets because of the domains’ wide ranges of function and highly conserved binding pockets. The PICK1 PDZ domain has been proposed as a possible drug target because the interactions between the PICK1 PDZ domain
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The PDZ family has drawn attention as possible drug targets because of the domains’ wide ranges of function and highly conserved binding pockets. The PICK1 PDZ domain has been proposed as a possible drug target because the interactions between the PICK1 PDZ domain and the GluA2 subunit of the AMPA receptor have been shown to progress neurodegenerative diseases. BIO124 has been identified as a sub µM inhibitor of the PICK1–GluA2 interaction. Here, we use all-atom molecular dynamics simulations to reveal the atomic-level interaction pattern between the PICK1 PDZ domain and BIO124. Our simulations reveal three unique binding conformations of BIO124 in the PICK1 PDZ binding pocket, referred to here as state 0, state 1, and state 2. Each conformation is defined by a unique hydrogen bonding network and a unique pattern of hydrophobic interactions between BIO124 and the PICK1 PDZ domain. Interestingly, each conformation of BIO124 results in different dynamic changes to the PICK1 PDZ domain. Unlike states 1 and 2, state 0 induces dynamic coupling between BIO124 and the αA helix. Notably, this dynamic coupling with the αA helix is similar to what has been observed in other PDZ–ligand complexes. Our analysis indicates that the interactions formed between BIO124 and I35 may be the key to inducing dynamic coupling with the αA helix. Lastly, we suspect that the conformational shifts observed in our simulations may affect the stability and thus the overall effectiveness of BIO124. We propose that a physically larger inhibitor may be necessary to ensure sufficient interactions that permit stable binding between a drug and the PICK1 PDZ domain.
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(This article belongs to the Topic Computer-Based Solutions to Investigate Biological- and Health-Related Problems)
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Open AccessArticle
Spectral Library-Based Single-Cell Proteomics Resolves Cellular Heterogeneity
Cells 2022, 11(15), 2450; https://doi.org/10.3390/cells11152450 - 07 Aug 2022
Abstract
Dissecting the proteome of cell types and states at single-cell resolution, while being highly challenging, has significant implications in basic science and biomedicine. Mass spectrometry (MS)-based single-cell proteomics represents an emerging technology for system-wide, unbiased profiling of proteins in single cells. However, significant
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Dissecting the proteome of cell types and states at single-cell resolution, while being highly challenging, has significant implications in basic science and biomedicine. Mass spectrometry (MS)-based single-cell proteomics represents an emerging technology for system-wide, unbiased profiling of proteins in single cells. However, significant challenges remain in analyzing an extremely small amount of proteins collected from a single cell, as a proteome-wide amplification of proteins is not currently feasible. Here, we report an integrated spectral library-based single-cell proteomics (SLB-SCP) platform that is ultrasensitive and well suited for a large-scale analysis. To overcome the low MS/MS signal intensity intrinsically associated with a single-cell analysis, this approach takes an alternative approach by extracting a breadth of information that specifically defines the physicochemical characteristics of a peptide from MS1 spectra, including monoisotopic mass, isotopic distribution, and retention time (hydrophobicity), and uses a spectral library for proteomic identification. This conceptually unique MS platform, coupled with the DIRECT sample preparation method, enabled identification of more than 2000 proteins in a single cell to distinguish different proteome landscapes associated with cellular types and heterogeneity. We characterized individual normal and cancerous pancreatic ductal cells (HPDE and PANC-1, respectively) and demonstrated the substantial difference in the proteomes between HPDE and PANC-1 at the single-cell level. A significant upregulation of multiple protein networks in cancer hallmarks was identified in the PANC-1 cells, functionally discriminating the PANC-1 cells from the HPDE cells. This integrated platform can be built on high-resolution MS and widely accepted proteomic software, making it possible for community-wide applications.
Full article
(This article belongs to the Special Issue Deciphering the Proteome in Cell Biology and Diseases)
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Open AccessReview
Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer
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, , , , , , and
Cells 2022, 11(15), 2449; https://doi.org/10.3390/cells11152449 - 07 Aug 2022
Abstract
Prostate cancer belongs in the class of hormone-dependent cancers, representing a major cause of cancer incidence in men worldwide. Since upon disease onset almost all prostate cancers are androgen-dependent and require active androgen receptor (AR) signaling for their survival, the primary treatment approach
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Prostate cancer belongs in the class of hormone-dependent cancers, representing a major cause of cancer incidence in men worldwide. Since upon disease onset almost all prostate cancers are androgen-dependent and require active androgen receptor (AR) signaling for their survival, the primary treatment approach has for decades relied on inhibition of the AR pathway via androgen deprivation therapy (ADT). However, following this line of treatment, cancer cell pools often become resistant to therapy, contributing to disease progression towards the significantly more aggressive castration-resistant prostate cancer (CRPC) form, characterized by poor prognosis. It is, therefore, of critical importance to elucidate the molecular mechanisms and signaling pathways underlying the progression of early-stage prostate cancer towards CRPC. In this review, we aim to shed light on the role of major signaling pathways including the DNA damage response (DDR) and the developmental Hippo and Notch pathways in prostate tumorigenesis. We recapitulate key evidence demonstrating the crosstalk of those pathways as well as with pivotal prostate cancer-related ‘hubs’ such as AR signaling, and evaluate the clinical impact of those interactions. Moreover, we attempt to identify molecules of the complex DDR–Hippo–Notch interplay comprising potentially novel therapeutic targets in the battle against prostate tumorigenesis.
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(This article belongs to the Special Issue Multitasking Proteins and Their Involvement in Pathogenesis)
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Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities
by
, , , , and
Cells 2022, 11(15), 2448; https://doi.org/10.3390/cells11152448 - 07 Aug 2022
Abstract
Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor.
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Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.
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(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)
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Investigation of Radiotracer Metabolic Stability In Vitro with CYP-Overexpressing Hepatoma Cell Lines
by
, , , , , and
Cells 2022, 11(15), 2447; https://doi.org/10.3390/cells11152447 - 07 Aug 2022
Abstract
The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability, little or no information is obtained
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The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability, little or no information is obtained on cytochrome P450 (CYP) enzyme and isoform-specific contribution to the metabolic fate of individual radiotracers. Herein, we investigated recently established CYP-overexpressing hepatoblastoma cell lines (HepG2) for their suitability to study the metabolic stability of radiotracers in general and to gain insight into CYP isoform specificity. Wildtype HepG2 and CYP1A2-, CYP2C19-, and CYP3A4-overexpressing HepG2 cells were incubated with radiotracers, and metabolic turnover was analyzed. The optimized protocol, covering cell seeding in 96-well plates and analysis of supernatant by radio thin-layer-chromatography for higher throughput, was transferred to the evaluation of three 18F-labeled celecoxib-derived cyclooxygenase-2 inhibitors (coxibs). These investigations revealed time-dependent degradation of the intact radiotracers, as well as CYP isoform- and substrate-specific differences in their metabolic profiles. HepG2 CYP2C19 proved to be the cell line showing the highest metabolic turnover for each radiotracer studied here. Comparison with human and murine liver microsome assays showed good agreement with the human metabolite profile obtained by the HepG2 cell lines. Therefore, CYP-overexpressing HepG2 cells provide a good complement for assessing the metabolic stability of radiotracers and allow the analysis of the CYP isoform-specific contribution to the overall radiotracer metabolism.
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(This article belongs to the Collection Advances in Cell Culture and Tissue Engineering)
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Phylogeny and Fatty Acid Profiles of New Pinnularia (Bacillariophyta) Species from Soils of Vietnam
Cells 2022, 11(15), 2446; https://doi.org/10.3390/cells11152446 - 07 Aug 2022
Abstract
We studied the morphology, ultrastructure, and phylogeny of eight soil diatom strains assigned to the Pinnularia genus. Six of these strains, identified by us as new species, are described for the first time. We provide a comprehensive comparison with related species and include
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We studied the morphology, ultrastructure, and phylogeny of eight soil diatom strains assigned to the Pinnularia genus. Six of these strains, identified by us as new species, are described for the first time. We provide a comprehensive comparison with related species and include ecological data. Molecular phylogeny reconstruction using 18S rDNA and rbcL affiliates the new strains with different subclades within Pinnularia, including ‘borealis’, ‘grunowii’ and ‘stomatophora’. We also studied the fatty acid profiles in connection with the emerging biotechnological value of diatoms as a source of lipids. Stearic (36.0–64.4%), palmitic (20.1–30.4%), and palmitoleic (up to 20.8%) acids were the dominant fatty acids in the algae cultured on Waris-H + Si medium. High yields of saturated and monounsaturated fatty acids position the novel Pinnularia strains as a promising feedstock for biofuel production.
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(This article belongs to the Special Issue Growth and Division in Algae)

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