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Annals of Thoracic and Cardiovascular... Oct 2022Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of...
BACKGROUND
Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of hsa_circ_0079530 (circ_0079530) in NSCLC development and radiosensitivity are largely unknown.
METHODS
The abundances of circ_0079530, microRNA (miR-409-3p), aquaporin 4 (AQP4), E-cadherin, intercellular adhesion molecule-1, vitronectin, proliferating cell nuclear antigen, and matrix metalloproteinase 9 were determined via quantitative reverse transcription polymerase chain reaction or western blotting. Cell proliferation, survival fraction, cycle process, migration, invasion, and in vivo growth were examined by cell counting kit-8, colony formation, flow cytometry, transwell, and xenograft analyses. The binding relationship was assessed via dual-luciferase reporter assay and RNA immunoprecipitation assay.
RESULTS
Circ_0079530 expression was increased in NSCLC tissues and radioresistant samples. Circ_0079530 knockdown restrained cell proliferation, migration, and invasion, and facilitated radiosensitivity. Circ_0079530 silence decreased tumor growth with or without radiation treatment. Circ_0079530 was verified as a miR-409-3p sponge, and miR-409-3p downregulation mitigated the effects of circ_0079530 interference on NSCLC cell malignancy and radiosensitivity. AQP4 was directly targeted by miR-409-3p. MiR-409-3p restrained cell proliferation, migration, and invasion, and enhanced radiosensitivity by decreasing AQP4 expression. Notably, circ_0079530 silence decreased AQP4 expression by regulating miR-409-3p expression.
CONCLUSION
Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.
Topics: Humans; Aquaporin 4; Cadherins; Carcinoma, Non-Small-Cell Lung; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Intercellular Adhesion Molecule-1; Lung Neoplasms; Matrix Metalloproteinase 9; MicroRNAs; Proliferating Cell Nuclear Antigen; Radiation Tolerance; RNA, Circular; Treatment Outcome; Vitronectin
PubMed: 35896371
DOI: 10.5761/atcs.oa.21-00237 -
Clinical & Translational Immunology 2019γδ T cells are fascinating cells that bridge the innate and adaptive immune systems. They have long been known to proliferate rapidly following infection; however, the... (Review)
Review
γδ T cells are fascinating cells that bridge the innate and adaptive immune systems. They have long been known to proliferate rapidly following infection; however, the identity of the specific γδ T cell subsets proliferating and the role of this expansion in protection from disease have only been explored more recently. Several recent studies have investigated γδ T-cell responses to vaccines targeting infections such as , and influenza, and studies in animal models have provided further insight into the association of these responses with improved clinical outcomes. In this review, we examine the evidence for a role for γδ T cells in vaccine-induced protection against various bacterial, protozoan and viral infections. We further discuss results suggesting potential mechanisms for protection, including cytokine-mediated direct and indirect killing of infected cells, and highlight remaining open questions in the field. Finally, building on current efforts to integrate strategies targeting γδ T cells into immunotherapies for cancer, we discuss potential approaches to improve vaccines for infectious diseases by inducing γδ T-cell activation and cytotoxicity.
PubMed: 31485329
DOI: 10.1002/cti2.1072 -
Scientific Reports Sep 2021Inducing cardiac myocytes to proliferate is considered a potential therapy to target heart disease, however, modulating cardiac myocyte proliferation has proven to be a...
Inducing cardiac myocytes to proliferate is considered a potential therapy to target heart disease, however, modulating cardiac myocyte proliferation has proven to be a technical challenge. The Hippo pathway is a kinase signaling cascade that regulates cell proliferation during the growth of the heart. Inhibition of the Hippo pathway increases the activation of the transcription factors YAP/TAZ, which translocate to the nucleus and upregulate transcription of pro-proliferative genes. The Hippo pathway regulates the proliferation of cancer cells, pluripotent stem cells, and epithelial cells through a cell-cell contact-dependent manner, however, it is unclear if cell density-dependent cell proliferation is a consistent feature in cardiac myocytes. Here, we used cultured human iPSC-derived cardiac myocytes (hiCMs) as a model system to investigate this concept. hiCMs have a comparable transcriptome to the immature cardiac myocytes that proliferate during heart development in vivo. Our data indicate that a dense syncytium of hiCMs can regain cell cycle activity and YAP expression and activity when plated sparsely or when density is reduced through wounding. We found that combining two small molecules, XMU-MP-1 and S1P, increased YAP activity and further enhanced proliferation of low-density hiCMs. Importantly, these compounds had no effect on hiCMs within a dense syncytium. These data add to a growing body of literature that link Hippo pathway regulation with cardiac myocyte proliferation and demonstrate that regulation is restricted to cells with reduced contact inhibition.
Topics: Adaptor Proteins, Signal Transducing; Base Sequence; Cell Count; Cell Cycle; Cell Differentiation; Cell Division; Cells, Cultured; Contact Inhibition; Hippo Signaling Pathway; Humans; Induced Pluripotent Stem Cells; Lysophospholipids; Myocytes, Cardiac; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases; RNA; Signal Transduction; Sphingosine; Sulfonamides; Transcription Factors; YAP-Signaling Proteins
PubMed: 34493746
DOI: 10.1038/s41598-021-97133-6 -
Dermatopathology (Basel, Switzerland) Aug 2021The term "pseudomalignancy" covers a large, heterogenous group of diseases characterized by a benign cellular proliferation, hyperplasia, or infiltrate that resembles a... (Review)
Review
The term "pseudomalignancy" covers a large, heterogenous group of diseases characterized by a benign cellular proliferation, hyperplasia, or infiltrate that resembles a true malignancy clinically or histologically. Here, we (i) provide a non-exhaustive review of several inflammatory skin diseases and benign skin proliferations that can mimic a malignant neoplasm in children, (ii) give pathologists some helpful clues to guide their diagnosis, and (iii) highlight pitfalls to be avoided. The observation of clinical-pathological correlations is often important in this situation and can sometimes be the only means (along with careful monitoring of the disease's clinical course) of reaching a firm diagnosis.
PubMed: 34449607
DOI: 10.3390/dermatopathology8030042 -
Cell Proliferation Jan 2020Clinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by...
OBJECTIVE
Clinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by keratinocyte hyperproliferation and inflammation. The present study investigates the efficacy of tryptanthrin, a bioactive compound in indigo naturalis, against non-melanoma skin cancer (NMSC) and the signalling events involved.
METHODS
Efficacy of tryptanthrin against NMSC was assessed using DMBA/PMA-induced skin carcinogenesis model in Swiss albino mice. Immunostaining for PCNA and ki-67 was used to mark proliferating cells in tissues. Haematoxylin and eosin staining and toluidine staining were employed to assess inflammation, and TUNEL assay was used to detect apoptosis in tissues. The signalling events were evaluated using Western blot, imunohistochemistry and immunofluorescence staining. MTT assay and clonogenic assay were performed to assess the viability and proliferation of cancer cells, in vitro.
RESULTS
In mice, topical application of tryptanthrin suppressed skin carcinogenesis. It attenuated inflammation, impeded the proliferation of hair follicle (HF) cells and suppressed the activation of β-catenin, a major driver of HF cell proliferation. Additionally tryptanthrin suppressed the activation of ERK1/2 and p38, both of which promote β-catenin activation and lowered the expression of c-Myc and cyclin-D1. Tryptanthrin suppressed the proliferation of the human NMSC cell line, A431 and abrogated EGF-induced activation of β-catenin and subsequent cytoskeletal rearrangement.
CONCLUSION
The study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.
Topics: Animals; Drug Screening Assays, Antitumor; Ki-67 Antigen; Mice; Neoplasm Proteins; Proliferating Cell Nuclear Antigen; Quinazolines; Skin Neoplasms; Tetradecanoylphorbol Acetate; gamma-Aminobutyric Acid
PubMed: 31663659
DOI: 10.1111/cpr.12710 -
Indian Journal of Dermatology,... 2023Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum.
BACKGROUND
Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum.
AIMS
This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum.
MATERIALS AND METHODS
All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out.
RESULTS
Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases.
LIMITATIONS
Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed.
CONCLUSION
Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.
Topics: Humans; Tubular Sweat Gland Adenomas; Sweat Gland Neoplasms; Retrospective Studies; Proto-Oncogene Proteins B-raf; Hyperplasia; Carcinoma, Squamous Cell
PubMed: 34623039
DOI: 10.25259/IJDVL_845_20 -
Frontiers in Oncology 2020Large granular lymphocyte leukemia (LGLL) is a chronic proliferation of clonal cytotoxic lymphocytes, usually presenting with cytopenias and yet lacking a specific... (Review)
Review
Large granular lymphocyte leukemia (LGLL) is a chronic proliferation of clonal cytotoxic lymphocytes, usually presenting with cytopenias and yet lacking a specific therapy. The disease is heterogeneous, including different subsets of patients distinguished by LGL immunophenotype (CD8+ Tαβ, CD4+ Tαβ, Tγδ, NK) and the clinical course of the disease (indolent/symptomatic/aggressive). Even if the etiology of LGLL remains elusive, evidence is accumulating on the genetic landscape driving and/or sustaining chronic LGL proliferations. The most common gain-of-function mutations identified in LGLL patients are on and genes, which have been recently recognized as clonal markers and were included in the 2017 WHO classification of the disease. A significant correlation between mutations and symptomatic disease has been highlighted. At variance, mutations could have a different clinical impact based on the immunophenotype of the mutated clone. In fact, they are regarded as the signature of an aggressive clinical course with a poor prognosis in CD8+ T-LGLL and aggressive NK cell leukemia, while they are devoid of negative prognostic significance in CD4+ T-LGLL and Tγδ LGLL. Knowing the specific distribution of mutations helps identify the discrete mechanisms sustaining LGL proliferations in the corresponding disease subsets. Some patients equipped with wild type genes are characterized by less frequent mutations in different genes, suggesting that other pathogenetic mechanisms are likely to be involved. In this review, we discuss how the LGLL mutational pattern allows a more precise and detailed tumor stratification, suggesting new parameters for better management of the disease and hopefully paving the way for a targeted clinical approach.
PubMed: 32133291
DOI: 10.3389/fonc.2020.00152 -
Archives of Medical Science : AMS 2021Aging is a natural process involving dysfunction of multiple organs and is characterized by increased susceptibility to infections, cancer and autoimmune diseases. The...
INTRODUCTION
Aging is a natural process involving dysfunction of multiple organs and is characterized by increased susceptibility to infections, cancer and autoimmune diseases. The functionality of the immune system depends on the capacity of lymphocytes to proliferate in response to antigenic challenges, and telomere length has an important role regulating the number of cell divisions. The aim of this study was to determine the possible relationship between telomere length, interleukin 2 (IL-2) production, CD25 expression and proliferation of peripheral blood mononuclear cells (PBMCs) in aged men.
MATERIAL AND METHODS
Telomere length was measured by RT-PCR in PBMCs from young and aged men. IL-2 production and CD25 expression were determined by ELISA and flow cytometry, respectively. Cell proliferation was measured by CFSE dilution assays upon stimulation with concanavalin A (Con A).
RESULTS
PBMCs from aged men showed a shorter telomere length and a reduced capacity to proliferate , compared to young men. In contrast, no significant differences in the level of CD25 expression on T lymphocytes, and production of IL-2 were detected in both groups. In addition, no significant correlation was detected between levels of CD25 expression, IL-2 production, cell proliferation, and telomere length in aged men.
CONCLUSIONS
In aged men the telomere length shortening and the reduced T cell proliferation are not related to the capacity of IL-2 production and CD25 expression on T lymphocytes.
PubMed: 34025848
DOI: 10.5114/aoms.2019.87593 -
EvoDevo Jun 2022There are a wide range of developmental strategies in animal phyla, but most insights into adult body plan formation come from direct-developing species. For...
BACKGROUND
There are a wide range of developmental strategies in animal phyla, but most insights into adult body plan formation come from direct-developing species. For indirect-developing species, there are distinct larval and adult body plans that are linked together by metamorphosis. Some outstanding questions in the development of indirect-developing organisms include the extent to which larval tissue undergoes cell death during the process of metamorphosis and when and where the tissue that will give rise to the adult originates. How do the processes of cell division and cell death redesign the body plans of indirect developers? In this study, we present patterns of cell proliferation and cell death during larval body plan development, metamorphosis, and adult body plan formation, in the hemichordate Schizocardium californium (Cameron and Perez in Zootaxa 3569:79-88, 2012) to answer these questions.
RESULTS
We identified distinct patterns of cell proliferation between larval and adult body plan formation of S. californicum. We found that some adult tissues proliferate during the late larval phase prior to the start of overt metamorphosis. In addition, using an irradiation and transcriptomic approach, we describe a genetic signature of proliferative cells that is shared across the life history states, as well as markers that are unique to larval or juvenile states. Finally, we observed that cell death is minimal in larval stages but begins with the onset of metamorphosis.
CONCLUSIONS
Cell proliferation during the development of S. californicum has distinct patterns in the formation of larval and adult body plans. However, cell death is very limited in larvae and begins during the onset of metamorphosis and into early juvenile development in specific domains. The populations of cells that proliferated and gave rise to the larvae and juveniles have a genetic signature that suggested a heterogeneous pool of proliferative progenitors, rather than a set-aside population of pluripotent cells. Taken together, we propose that the gradual morphological transformation of S. californicum is mirrored at the cellular level and may be more representative of the development strategies that characterize metamorphosis in many metazoan animals.
PubMed: 35668535
DOI: 10.1186/s13227-022-00198-1 -
Stem Cell Research & Therapy Jan 2021Adult mammalian retinal stem cells (RSCs) readily proliferate, self-renew, and generate progeny that differentiate into all retinal cell types in vitro. RSC-derived...
BACKGROUND
Adult mammalian retinal stem cells (RSCs) readily proliferate, self-renew, and generate progeny that differentiate into all retinal cell types in vitro. RSC-derived progeny can be induced to differentiate into photoreceptors, making them a potential source for retinal cell transplant therapies. Despite their proliferative propensity in vitro, RSCs in the adult mammalian eye do not proliferate and do not have a regenerative response to injury. Thus, identifying and modulating the mechanisms that regulate RSC proliferation may enhance the capacity to produce RSC-derived progeny in vitro and enable RSC activation in vivo.
METHODS
Here, we used medium-throughput screening to identify small molecules that can expand the number of RSCs and their progeny in culture. In vitro differentiation assays were used to assess the effects of synthetic glucocorticoid agonist dexamethasone on RSC-derived progenitor cell fate. Intravitreal injections of dexamethasone into adult mouse eyes were used to investigate the effects on endogenous RSCs.
RESULTS
We discovered that high-affinity synthetic glucocorticoid agonists increase RSC self-renewal and increase retinal progenitor proliferation up to 6-fold without influencing their differentiation in vitro. Intravitreal injection of synthetic glucocorticoid agonist dexamethasone induced in vivo proliferation in the ciliary epithelium-the niche in which adult RSCs reside.
CONCLUSIONS
Together, our results identify glucocorticoids as novel regulators of retinal stem and progenitor cell proliferation in culture and provide evidence that GCs may activate endogenous RSCs.
Topics: Animals; Cell Differentiation; Cell Proliferation; Cell Self Renewal; Cells, Cultured; Glucocorticoids; Mice; Retina
PubMed: 33494791
DOI: 10.1186/s13287-021-02136-9