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2.
BMC Genomics ; 23(1): 5, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983375

RESUMO

BACKGROUND: Aspergillus flavus, one of the causative agents of human fungal keratitis, can be phagocytosed by human corneal epithelial (HCE) cells and the conidia containing phagosomes mature into phagolysosomes. But the immunological responses of human corneal epithelial cells interacting with A. flavus are not clear. In this study, we report the expression of immune response related genes of HCE cells exposed to A. flavus spores using targeted transcriptomics. METHODS: Human corneal epithelial cell line and primary cultures were grown in a six-well plate and used for coculture experiments. Internalization of the conidia was confirmed by immunofluorescence microscopy of the colocalized endosomal markers CD71 and LAMP1. Total RNA was isolated, and the quantity and quality of the isolated RNA were assessed using Qubit and Bioanalyzer. NanoString nCounter platform was used for the analysis of mRNA abundance using the Human Immunology panel. R-package and nSolver software were used for data analysis. KEGG and FunRich 3.1.3 tools were used to analyze the differentially expressed genes. RESULTS: Different morphotypes of conidia were observed after 6 h of coculture with human corneal epithelial cells and found to be internalized by epithelial cells. NanoString profiling showed more than 20 differentially expressed genes in immortalized human corneal epithelial cell line and more than ten differentially expressed genes in primary corneal epithelial cells. Distinct set of genes were altered in their expression in cell line and primary corneal epithelial cells. KEGG pathway analysis revealed that genes associated with TNF signaling, NF-KB signaling, and Th17 signaling were up-regulated, and genes associated with chemokine signaling and B cell receptor signaling were down regulated. FunRich pathway analysis showed that pathways such as CDC42 signaling, PI3K signaling, and Arf6 trafficking events were activated by the clinical isolates CI1123 and CI1698 in both type of cells. CONCLUSIONS: Combining the transcript analysis data from cell lines and primary cultures, we showed the up regulation of immune defense genes in A. flavus infected cells. At the same time, chemokine signaling and B cell signaling pathways are downregulated. The variability in the expression levels in the immortalized cell line and the primary cultures is likely due to the variable epigenetic reprogramming in the immortalized cells and primary cultures in the absence of any changes in the genome. It highlights the importance of using both cell types in host-pathogen interaction studies.


Assuntos
Aspergillus flavus , Células Epiteliais/imunologia , Regulação da Expressão Gênica/imunologia , Aspergillus flavus/genética , Linhagem Celular , Quimiocinas/imunologia , Córnea/citologia , Córnea/microbiologia , Células Epiteliais/microbiologia , Humanos , Imunidade , Transdução de Sinais , Esporos Fúngicos
3.
Cell Mol Life Sci ; 79(1): 22, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981210

RESUMO

The three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we used in situ high-throughput chromosome conformation (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to characterize the high-order chromatin structure signature of female germline stem cells (FGSCs) and identify its regulating key factor based on the data-driven of multiple omics data. By comparison with pluripotent stem cells (PSCs), adult stem cells (ASCs), and somatic cells at three major levels of chromatin architecture, A/B compartments, topologically associating domains, and chromatin loops, the chromatin architecture of FGSCs was most similar to that of other ASCs and largely different from that of PSCs and somatic cells. After integrative analysis of the three-dimensional chromatin structure, active compartment-associating loops (aCALs) were identified as a signature of high-order chromatin organization in FGSCs, which revealed that CCCTC-binding factor was a major factor to maintain the properties of FGSCs through regulation of aCALs. We found FGSCs belong to ASCs at chromatin structure level and characterized aCALs as the high-order chromatin structure signature of FGSCs. Furthermore, CTCF was identified to play a key role in regulating aCALS to maintain the biological functions of FGSCs. These data provide a valuable resource for future studies of the features of chromatin organization in mammalian stem cells and further understanding of the fundamental characteristics of FGSCs.


Assuntos
Fator de Ligação a CCCTC/metabolismo , Genoma , Imageamento Tridimensional , Células-Tronco de Oogônios/metabolismo , Células-Tronco Adultas/metabolismo , Animais , Sequência de Bases , Forma Celular , Cromatina/metabolismo , Cromossomos de Mamíferos/metabolismo , Feminino , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Células-Tronco de Oogônios/citologia
4.
EMBO J ; 41(1): e108843, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981518

RESUMO

Primary cilia are antenna-like organelles required for signalling transduction. How cilia structure is mechanistically maintained at steady-state to promote signalling is largely unknown. Here, we define that mammalian primary cilia axonemes are formed by proximal segment (PS) and distal segment (DS) delineated by tubulin polyglutamylation-rich and -poor regions, respectively. The analysis of proximal/distal segmentation indicated that perturbations leading to cilia over-elongation influenced PS or DS length with a different impact on cilia behaviour. We identified septins as novel repressors of DS growth. We show that septins control the localisation of MKS3 and CEP290 required for a functional transition zone (TZ), and the cilia tip accumulation of the microtubule-capping kinesin KIF7, a cilia-growth inhibitor. Live-cell imaging and analysis of sonic-hedgehog (SHH) signalling activation established that DS over-extension increased cilia ectocytosis events and decreased SHH activation. Our data underlines the importance of understanding cilia segmentation for length control and cilia-dependent signalling.


Assuntos
Cílios/metabolismo , Septinas/metabolismo , Animais , Antígenos de Neoplasias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Proteínas do Citoesqueleto/metabolismo , Proteínas Hedgehog/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Microtúbulos/metabolismo , Epitélio Pigmentado da Retina/citologia , Transdução de Sinais
5.
Ultrasonics ; 119: 106601, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34624581

RESUMO

Herein, we propose a method to estimate the reflection coefficient of the ultrasonic wave transmitted onto an object and to display this with acoustic impedance distribution. The observation targets were glial cells, which have a rigid cytoskeleton and spread out well on a culture substrate. A reflection coefficient derived only from the cells was then obtained using a deconvolution process. In the conventional method, the deconvolution process that was performed only in the frequency domain would cause an error in the reconstructed signal, and it formed an artifact when the result was converted into the acoustic impedance image. To solve this problem, two types of deconvolution techniques were applied in either the full frequency or time-frequency domain. The results of both methods were then compared. Since the characteristic acoustic impedance is a physical property substantially equivalent to the bulk modulus, it can be considered that the internal elastic parameter is thus estimated. An analysis of the nucleus based on its position in the acoustic impedance image was then performed. The results indicated that the proposed time-frequency domain deconvolution method is able to maintain the structure of the cell, while the cell itself is free from unwanted artifacts. The nucleus was also estimated to be located toward the center of the cell, with lower acoustic impedance value than the cytoskeleton. The results of this study could contribute to establishing a method for monitoring the internal condition of cultured cells in regenerative medicine and drug discovery.


Assuntos
Microscopia Acústica/métodos , Neuroglia/ultraestrutura , Animais , Células Cultivadas , Cerebelo/citologia , Análise dos Mínimos Quadrados , Ratos , Transdutores
6.
Gene ; 809: 146001, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34637898

RESUMO

The function of the Agtpbp1 gene has mainly been delineated by studying Agtpbp1pcd (pcd) mutant mice, characterized by losses in cerebellar Purkinje and granule cells along with degeneration of retinal photoreceptors, mitral cells of the olfactory bulb, thalamic neurons, and alpha-motoneurons. As a result of cerebellar degeneration, cerebellar GABA and glutamate concentrations in Agtpbp1pcd mutants decreased while monoamine concentrations increased. The salient behavioral phenotypes include cerebellar ataxia, a loss in motor coordination, and cognitive deficits. Similar neuropathogical and behavioral profiles have been described in childhood-onset human subjects with biallelic variants of AGTPBP1, including cerebellar ataxia and hypotonia.


Assuntos
Cerebelo/fisiologia , Proteínas de Ligação ao GTP/genética , Doenças Neurodegenerativas/patologia , D-Ala-D-Ala Carboxipeptidase Tipo Serina/genética , Animais , Cerebelo/citologia , Cricetinae , Proteínas de Ligação ao GTP/metabolismo , Humanos , Camundongos Mutantes , Doenças Neurodegenerativas/genética , Células de Purkinje/patologia , Células de Purkinje/fisiologia , D-Ala-D-Ala Carboxipeptidase Tipo Serina/metabolismo , Ovinos
7.
Chem Biol Interact ; 352: 109783, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34932953

RESUMO

This paper provides an identification and detailed assessment of hormetic dose responses of embryonic stem cells (ESCs) with particular emphasis on cell renewal (proliferation) and differentiation, underlying mechanistic foundations and potential therapeutic implications. Hormetic dose responses were commonly reported, being induced by a broad range of chemicals, including pharmaceuticals (e.g., atorvastatin, isoproterenol, lithium, nicotine, ouabain), dietary supplements (e.g., curcumin, multiple ginsenosides, resveratrol), endogenous agents (e.g., estrogen, hydrogen peroxide, melatonin), and physical stressor agents (e.g., hypoxia, ionizing radiation). ESC-hormetic dose responses are similar for other stem cell types (e.g., adipose-derived stem cells, apical papilla, bone marrow stem cells, dental pulp stem cells, endothelial stem cells, muscle stem cells, periodontal ligament stem cells, neural stem cells), indicating a high degree of generality for the hormetic-stem cells response. The widespread occurrence of hormetic dose responses shown by ESCs and other stem cells suggests that the hormetic dose response may represent a fundamental and highly conserved evolutionary strategy.


Assuntos
Células-Tronco Embrionárias/efeitos dos fármacos , Hormese , Animais , Evolução Biológica , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Ácidos Graxos/administração & dosagem , Hormese/fisiologia , Humanos
8.
Chem Biol Interact ; 352: 109782, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34932954

RESUMO

Indole derivatives from various plants are known to have health benefits because of their anti-cancer, anti-oxidant, anti-inflammatory, and anti-tubercular effects. However, their effects on adipogenesis have not been fully elucidated yet. Herein, we show that a newly synthesized indole derivative, CF3-allylated indole, [(E)-1-(pyrimidin- 2-yl)-2-(4,4,4- trifluorobut-2-enyl)-1H-indole], effectively inhibits adipogenesis. We found that CF3-allylated indole inhibited lipid accumulation and suppressed the expression of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator activated receptor γ (PPARγ) in 3T3-L1 cells. The inhibitory effect of CF3-allylated indole primarily occurred at the early phase of adipocyte differentiation by increasing intracellular cyclic adenosine monophosphate (cAMP) levels and enhancing protein kinase A (PKA) and adenosine monophosphate-activated protein kinase (AMPK) signaling. Conversely, depletion of PKA or treatment with a protein kinase A inhibitor (H89) reversed such inhibitory effects of CF3-allylated indole on adipogenesis and PPARγ expression. These results suggest that CF3-allylated indole inhibits early stages of adipogenesis by increasing phosphorylation of PKA/AMPK, leading to decreased expression of adipogenic genes in 3T3-L1 cells. These results indicate that CF3-allylated indole has potential for controlling initial adipocyte differentiation in metabolic disorders such as obesity.


Assuntos
Adipogenia/efeitos dos fármacos , Indóis/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/genética , Adipogenia/fisiologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Expressão Gênica/efeitos dos fármacos , Indóis/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Obesidade/tratamento farmacológico , Fosforilação , Transdução de Sinais/efeitos dos fármacos
9.
Biochim Biophys Acta Gen Subj ; 1866(1): 130023, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626748

RESUMO

Humanin, a mitochondria-derived peptide, has been found to exert variously protective function in many tissues, especially in the nervous tissues. However, relatively limited studies have focused on the role of humanin in the regulation of reproduction. Current observations indicate that humanin plays an important role in regulating the response of the cell to oxidative stress and apoptosis in ovaries and testes via the modulation of several signaling pathways, especially when the body is in an abnormal state. Even so, the detailed mechanism of humanin function needs to be explored urgently. In this passage, we demonstrate how humanin exerts its protective role in female and male reproduction and raise several questions that need further investigations. Given humanin's new frontier for the design of novel therapeutic approaches for male infertility, male contraception, female infertility, and glucose metabolism in polycystic ovary syndrome, it is worthy of further study on its protective effects and clinical applications in reproductive function.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Reprodução/fisiologia , Feminino , Fertilidade/fisiologia , Líquido Folicular/citologia , Líquido Folicular/metabolismo , Humanos , Masculino , Ovário/metabolismo , Transdução de Sinais , Testículo/metabolismo
10.
Physiol Rev ; 102(1): 7-60, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33880962

RESUMO

The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing a haploid nucleus and the acrosomal exocytotic granule, and the flagellum, which generates energy and propels the cell; both structures are connected by the neck. The sperm's main aim is to participate in fertilization, thus activating development. Despite this common bauplan and function, there is an enormous diversity in structure and performance of sperm cells. For example, mammalian spermatozoa may exhibit several head patterns and overall sperm lengths ranging from ∼30 to 350 µm. Mechanisms of transport in the female tract, preparation for fertilization, and recognition of and interaction with the oocyte also show considerable variation. There has been much interest in understanding the origin of this diversity, both in evolutionary terms and in relation to mechanisms underlying sperm differentiation in the testis. Here, relationships between sperm bauplan and function are examined at two levels: first, by analyzing the selective forces that drive changes in sperm structure and physiology to understand the adaptive values of this variation and impact on male reproductive success and second, by examining cellular and molecular mechanisms of sperm formation in the testis that may explain how differentiation can give rise to such a wide array of sperm forms and functions.


Assuntos
Exocitose/fisiologia , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/fisiologia , Testículo/citologia , Animais , Evolução Biológica , Humanos , Masculino , Mamíferos/fisiologia , Espermatozoides/citologia
11.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34223880

RESUMO

Adipose tissue distribution in the human body is highly heterogeneous, and the relative mass of different depots is differentially associated with metabolic disease risk. Distinct functions of adipose depots are mediated by their content of specialized adipocyte subtypes, best exemplified by thermogenic adipocytes found in specific depots. Single-cell transcriptome profiling has been used to define the cellular composition of many tissues and organs, but the large size, buoyancy, and fragility of adipocytes have rendered it challenging to apply these techniques to understand the full complexity of adipocyte subtypes in different depots. Discussed here are strategies that have been recently developed for investigating adipocyte heterogeneity, including single-cell RNA-sequencing profiling of the stromal vascular fraction to identify diverse adipocyte progenitors, and single-nuclei profiling to characterize mature adipocytes. These efforts are yielding a more complete characterization of adipocyte subtypes in different depots, insights into the mechanisms of their development, and perturbations associated with different physiological states such as obesity. A better understanding of the adipocyte subtypes that compose different depots will help explain metabolic disease phenotypes associated with adipose tissue distribution and suggest new strategies for improving metabolic health.


Assuntos
Adipócitos/citologia , Tecido Adiposo/metabolismo , Adipogenia , Tecido Adiposo Bege/fisiologia , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/fisiologia , Animais , Estatura , Índice de Massa Corporal , Peso Corporal , Diferenciação Celular , Separação Celular , Humanos , Camundongos , Análise de Célula Única , Células-Tronco/citologia , Termogênese
12.
Int Endod J ; 55(1): 38-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34420220

RESUMO

AIM: To investigate the effects of butyric acid (BA), a metabolic product generated by pulp and root canal pathogens, on the viability and intercellular adhesion molecule-1 (ICAM-1) production of endothelial cells, which are crucial to angiogenesis and pulpal/periapical wound healing. METHODOLOGY: Endothelial cells were exposed to butyrate with/without inhibitors. Cell viability, apoptosis and reactive oxygen species (ROS) were evaluated using an MTT assay, PI/annexin V and DCF fluorescence flow cytometry respectively. RNA and protein expression was determined using a polymerase chain reaction assay and Western blotting or immunofluorescent staining. Soluble ICAM-1 (sICAM-1) was measured using an enzyme-linked immunosorbent assay. The quantitative results were expressed as mean ± standard error (SE) of the mean. The data were analysed using a paired Student's t-test where necessary. A p-value ≤0.05 was considered to indicate a statistically significant difference between groups. RESULTS: Butyrate (>4 mM) inhibited cell viability and induced cellular apoptosis and necrosis. It inhibited cyclin B1 but stimulated p21 and p27 expression. Butyrate stimulated ROS production and hemeoxygenase-1 (HO-1) expression as well as activated the Ac-H3, p-ATM, p-ATR, p-Chk1, p-Chk2, p-p38 and p-Akt expression of endothelial cells. Butyrate stimulated ICAM-1 mRNA/protein expression and significant sICAM-1 production (p < .05). Superoxide dismutase, 5z-7oxozeaenol, SB203580 and compound C (p <  .05), but not ZnPP, CGK733, AZD7762 or LY294002, attenuated butyrate cytotoxicity to endothelial cells. Notably, little effect on butyrate-stimulated sICAM-1 secretion was found. Valproic acid, phenylbutyrate and trichostatin (three histone deacetylase inhibitors) significantly induced sICAM-1 production (p < .05). CONCLUSION: Butyric acid inhibited proliferation, induced apoptosis, stimulated ROS and HO-1 production and increased ICAM-1 mRNA expression and protein synthesis in endothelial cells. Cell viability affected by BA was diminished by some inhibitors; however, the increased sICAM-1 secretion by BA was not affected by any of the tested inhibitors. These results facilitate understanding of the pathogenesis, prevention and treatment of pulpal/periapical diseases.


Assuntos
Ácido Butírico/farmacologia , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular , Doenças Periapicais , Células Cultivadas , Polpa Dentária/citologia , Humanos , Molécula 1 de Adesão Intercelular/metabolismo
13.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34534278

RESUMO

Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate mini-review in this collation of articles published in Endocrinology in 2020 and 2021, by Martchenko et al (Circadian rhythms and the gastrointestinal tract: relationship to metabolism and gut hormones); Alvarez et al (The microbiome as a circadian coordinator of metabolism); Seshadri and Doucette (Circadian regulation of the pancreatic beta cell); McCommis et al (The importance of keeping time in the liver); Oosterman et al (The circadian clock, shift work, and tissue-specific insulin resistance); and Heyde et al (Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in maintaining metabolic homeostasis.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano , Comportamento Alimentar , Homeostase , Fígado/fisiologia , Adipócitos/citologia , Animais , Endocrinologia/métodos , Ingestão de Energia , Metabolismo Energético/fisiologia , Retroalimentação Fisiológica , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Intestinos/fisiologia , Ilhotas Pancreáticas/citologia , Mamíferos/fisiologia , Doenças Metabólicas/metabolismo , Microbiota , Modelos Biológicos , Células Musculares/citologia , Músculo Esquelético/fisiologia
14.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34669927

RESUMO

Thyroid hormones (TH) are essential for skeletal development and adult bone homeostasis. Their bioavailability is determined by specific transporter proteins at the cell surface. The TH-specific transporter monocarboxylate transporter 8 (MCT8) was recently reported as a regulator of bone mass in mice. Given that high systemic triiodothyronine (T3) levels in Mct8 knockout (KO) mice are still able to cause trabecular bone loss, alternative TH transporters must substitute for MCT8 function in bone. In this study, we analyzed the skeletal phenotypes of male Oatp1c1 KO and Mct10 KO mice, which are euthyroid, and male Mct8/Oatp1c1 and Mct8/Mct10 double KO mice, which have elevated circulating T3 levels, to unravel the role of TH transport in bone. MicroCT analysis showed no significant trabecular bone changes in Oatp1c1 KO mice at 4 weeks and 16 weeks of age compared with wild-type littermate controls, whereas 16-week-old Mct8/Oatp1c1 double KO animals displayed trabecular bone loss. At 12 weeks, Mct10 KO mice, but not Mct8/Mct10 double KO mice, had decreased trabecular femoral bone volume with reduced osteoblast numbers. By contrast, lack of Mct10 in 24-week-old mice led to trabecular bone gain at the femur with increased osteoblast numbers and decreased osteoclast numbers whereas Mct8/Mct10 double KO did not alter bone mass. Neither Mct10 nor Mct8/Mct10 deletion affected vertebral bone structures at both ages. In vitro, osteoblast differentiation and activity were impaired by Mct10 and Mct8/Mct10-deficiency. These data demonstrate that MCT10, but not OATP1C1, is a site- and age-dependent regulator of bone mass and turnover in male mice.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Osso e Ossos/metabolismo , Animais , Transporte Biológico , Fenômenos Biomecânicos , Osso Esponjoso/metabolismo , Diferenciação Celular , Fêmur/fisiologia , Homeostase , Masculino , Camundongos , Camundongos Knockout , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteócitos/citologia , Fenótipo , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Tri-Iodotironina/metabolismo , Microtomografia por Raio-X
15.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718498

RESUMO

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations that actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system's role in lipid trafficking and mediating inflammation makes it a natural partner in regulating adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, whereas altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose crosstalk.


Assuntos
Tecido Adiposo/fisiologia , Sistema Linfático/fisiologia , Vasos Linfáticos/fisiologia , Adipócitos/citologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Diferenciação Celular , Células Endoteliais/metabolismo , Homeostase , Humanos , Inflamação , Lipídeos/química , Vasos Linfáticos/metabolismo , Camundongos , Obesidade/metabolismo
16.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791151

RESUMO

Cancer immunology is the most rapidly expanding field in cancer research, with the importance of immunity in cancer pathogenesis now well accepted including in the endocrine-related cancers. The immune system plays an essential role in the development of ductal and luminal epithelial differentiation in the mammary gland. Originally identified as evolutionarily conserved antipathogen cytokines, interferons (IFNs) have shown important immune-modulatory and antineoplastic properties when administered to patients with various types of cancer, including breast cancer. Recent studies have drawn attention to the role of tumor- and stromal-infiltrating lymphocytes in dictating therapy response and outcome of breast cancer patients, which, however, is highly dependent on the breast cancer subtype. The emerging role of tumor cell-inherent IFN signaling in the subtype-defined tumor microenvironment could influence therapy response with protumor activities in breast cancer. Here we review evidence with new insights into tumor cell-intrinsic and tumor microenvironment-derived IFN signaling, and the crosstalk of IFN signaling with key signaling pathways in estrogen receptor-positive (ER+) breast cancer. We also discuss clinical implications and opportunities exploiting IFN signaling to treat advanced ER+ breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/biossíntese , Interferons/metabolismo , Animais , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Diferenciação Celular , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Fibroblastos/metabolismo , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Linfócitos do Interstício Tumoral/citologia , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismo
17.
Mol Carcinog ; 61(1): 99-110, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34727382

RESUMO

E-cadherin plays a central role in the stability of epithelial tissues by facilitating cell-cell adhesion. Loss of E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT), a major event in the pathogenesis of several lung diseases. Our earlier studies showed that nickel, a ubiquitous environmental toxicant, induced EMT by persistently downregulating E-cadherin expression in human lung epithelial cells and that the EMT remained irreversible postexposure. However, the molecular basis of persistent E-cadherin downregulation by nickel exposure is not understood. Here, our studies show that the binding of transcription factor Sp1 to the promoter of E-cadherin encoding gene, CDH1, is essential for its expression. Nickel exposure caused a loss of Sp1 binding at the CDH1 promoter, resulting in its downregulation and EMT induction. Loss of Sp1 binding at the CDH1 promoter was associated with an increase in the binding of ZEB1 adjacent to the Sp1 binding site. ZEB1, an EMT master regulator persistently upregulated by nickel exposure, is a negative regulator of CDH1. CRISPR-Cas9-mediated knockout of ZEB1 restored Sp1 binding at the CDH1 promoter. Furthermore, ZEB1 knockout rescued E-cadherin expression and re-established the epithelial phenotype. Since EMT is associated with a number of nickel-exposure-associated chronic inflammatory lung diseases including asthma, fibrosis and cancer and metastasis, our findings provide new insights into the mechanisms associated with nickel pathogenesis.


Assuntos
Antígenos CD/genética , Caderinas/genética , Pulmão/citologia , Níquel/toxicidade , Fator de Transcrição Sp1/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular , Regulação para Baixo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Técnicas de Inativação de Genes , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Células MCF-7 , Regiões Promotoras Genéticas
18.
Parasitol Int ; 86: 102470, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34560288

RESUMO

During an investigation of parasitic ciliates in northern China, two Trichodina species, T. acuta Lom, 1970 and T. nigra Lom, 1960, were isolated from the freshwater fish Cyprinus carpio Linnaeus, 1758. The morphology of each species was investigated based on dry silver nitrate-stained specimens. In addition, the molecular phylogeny of each was analyzed based on small subunit ribosomal DNA (SSU rDNA) sequence data. Trichodina acuta can be distinguished from its congeners by the undefined periphery of the central circle, the distinct gap between the rays and the central circle, and the distinctly sickle-shaped blades. Trichodina nigra is a cosmopolitan ciliate and is characterized by its densely linked denticles, broad, rounded spatula-shaped blades, robust central parts, and well developed rays. Phylogenetic analyses revealed that T. acuta and T. nigra nest within different clades, supporting the assertion that the GC content of SSU rDNA sequences could reflect evolutionary relationships among Trichodina species.


Assuntos
Carpas , Infecções por Cilióforos/veterinária , Doenças dos Peixes/epidemiologia , Oligoimenóforos/classificação , Animais , China/epidemiologia , Infecções por Cilióforos/epidemiologia , Infecções por Cilióforos/parasitologia , Doenças dos Peixes/parasitologia , Oligoimenóforos/citologia , Oligoimenóforos/genética , Oligoimenóforos/isolamento & purificação , Filogenia , Prevalência
19.
Exp Cell Res ; 410(2): 112970, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34896076

RESUMO

Islet integrity plays a major role in maintaining glucose homeostasis and thus replenishment of damaged islets by differentiation of resident endocrine progenitors into neo islets regulates the islet functionality. Islet differentiation is affected by many factors including crosstalk with various organs by secretome. Adipose derived stem cells (ADSC) secrete a large array of factors in the extracellular milieu that exhibit regulatory effects on other tissues including pancreatic islets. The microenvironment of metabolically compromised human ADSCs (hADSCs) has a detrimental impact on islet functionality. In the present study, the role of secretome was studied on the differentiation of islets. Expression of key transcription factors like HNF-3B, NGN-3, NeuroD, PDX- 1, Maf-A, and GLUT-2 involved in development were differentially regulated in obese hADSC secretome as compared to control hADSC secretome. Islet like cell clusters (ILCCs) functionality and viability were critically hampered under obese hADSC secretome with compromised yield, morphometry, lower expression of C-peptide and Glucagon as well as higher ROS activity and cell death parameters. This study provides considerable insights on two major findings which are (i) exploring the use of hADSC secretome in islet differentiation and (ii) understanding the regulating effect of altered hADSC secretome under a metabolically compromised condition.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular , Ilhotas Pancreáticas/citologia , Células-Tronco/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Humanos , Camundongos , Obesidade/patologia , Fenótipo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Fatores de Tempo
20.
Exp Neurol ; 347: 113905, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34699790

RESUMO

Circular RNAs (circRNAs) are important for the development and regeneration of the nervous system. We investigated the differential expression profiles of circRNA induced by spinal cord injury and reported that circRNA_01477 facilitates spinal astrocyte proliferation and migration after injury in rats. In this study, we further clarified the function and possible mechanism of action of circRNA_01477 in neurons. Fluorescence in situ hybridization assay revealed that circRNA_01477 is mainly localized in the neuronal cytoplasm. Knockdown of circRNA_01477 significantly increased axonal length. The circRNA_01477/microRNAs (miRNA)/messenger RNA (mRNA) interaction network was investigated using RNA sequencing. miRNA-3075 showed a remarkable increase after circRNA_01477 depletion, and either overexpression of miRNA-3075 or downregulation of its target gene FosB significantly promoted axonal growth. Luciferase reporter assay showed that miRNA-3075 could directly bind to the 3'UTR of FosB and negatively regulated FosB transcription. Dual silencing of circRNA_01477 and miR-3075 revealed that miR-3075 inhibition rescued the increased axon length caused by siCircRNA_01477. Finally, we verified that the Stat3 pathway was activated after FosB protein depletion in rat spinal neurons, while the NF-κB pathway was not altered. In summary, our study is the first to report that circRNA_01477 contributes to axon growth by functioning as miRNA sponge by regulating the miRNA-3075/FosB/Stat3 axis.


Assuntos
Axônios/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Circular/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Células Cultivadas , Feminino , Gravidez , Ligação Proteica/fisiologia , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/citologia , Nervos Espinhais/metabolismo
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