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1.
J Transl Med ; 22(1): 86, 2024 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-38246999

RESUMEN

BACKGROUND: Obesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied. METHOD: Network pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets. RESULTS: The network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation's Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity. CONCLUSION: Overall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.


Asunto(s)
Enfermedades Cardiovasculares , Ácido Oleanólico , Animales , Simulación del Acoplamiento Molecular , Farmacología en Red , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , PPAR gamma
2.
Neurochem Res ; 49(5): 1291-1305, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38424396

RESUMEN

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons, with ferroptosis playing a significant role. Salidroside (SAL) has shown neuroprotective potential, this study aims to explore its capacity to mitigate ferroptosis in PD, focusing on the modulation of the Nuclear Factor E2-Related Factor 2 (Nrf2)/ Glutathione Peroxidase 4 (GPX4) pathway. Male C57BL/6 mice were subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, followed by SAL and Nrf2 inhibitor administration. Then behavioral tests, immunohistochemical staining, transmission electron microscopy, and Western blot analysis were conducted to assess motor functions, pathological changes, ferroptosis, and related protein expressions. In vitro, SH-SY5Y cells were treated with erastin to induce ferroptosis to assess the protective effects of SAL. Additionally, A53T-α-synuclein (α-syn) was used to stimulate the PD model, SAL and a Nrf2 inhibitor (ML385) was utilized to elucidate the role of the Nrf2/GPX4 pathway in mitigating ferroptosis in PD. In vivo, SAL significantly improved motor functions and reduced the expression of α-syn, while increasing tyrosine hydroxylase (TH) expression of PD mice. Additionally, SAL treatment notably enhanced the levels of antioxidants and reduced MDA and iron content in the substantia nigra of PD mice. In vitro, SAL treatment increased the TH, GPX4, Nrf2 expression, and mitochondrial membrane potential whereas alleviated ferroptosis through the Nrf2/GPX4 pathway, as evidenced in erastin-induced and α-syn overexpressing SH-SY5Y cells. While these effects were reversed upon Nrf2 inhibition. SAL demonstrates significant potential in mitigating PD pathology and ferroptosis, positioning the Nrf2/GPX4 pathway as a promising therapeutic target. However, future studies should focus on the long-term effects of SAL, its pharmacokinetics, addressing the multifactorial nature of PD pathogenesis.


Asunto(s)
Ferroptosis , Glucósidos , Neuroblastoma , Enfermedad de Parkinson , Fenoles , Masculino , Humanos , Ratones , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Ratones Endogámicos C57BL
3.
J Environ Manage ; 368: 122134, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39151340

RESUMEN

At present, it is estimated that approximately 800 million hectares of arable land worldwide is saline-alkali soil, which has become one of the major limiting factors restricting global agricultural productivity. Meanwhile, the residual food and excreta of mariculture animals, accompanied by potential eutrophication pollution, remain an unresolved issue due to salinity. In this study, the ameliorative effects of biochar (BC700) prepared from maricultural-solid-waste on the biological properties and physicochemical of saline-alkali soil and Salicornia europaea L growth were investigated. Supplements of 1, 3 and 5% BC700 significantly increased the total nitrogen, available phosphorus, available potassium and organic carbon in soil by 2.00-68.30%, 26.74-64.96%, 7.74-52.53% and 3.43-64.96%, respectively. And BC700 significantly reduced soil pH. This occurred with enhanced soil urease, sucrase and alkaline phosphatase activities and alterations to the bacterial community structure, thus improving P and N cycling and the soil physicochemical properties. In addition, BC700 has weakened the competition between saline soil microorganisms and also changed the key species of microbial networks. Co-utilization of BC700 and S. europaea cultivation could increase the stability of the soil microbial community while the growth of the plant was significantly promoted by 19.8-25.4%. Supplements of 3% BC700 are recommended as an eco-friendly and effective treatment for the recycling of mariculture wastes for the improvement of saline-alkali soils.


Asunto(s)
Carbón Orgánico , Suelo , Residuos Sólidos , Carbón Orgánico/química , Suelo/química , Nitrógeno , Fósforo/análisis , Fósforo/química , Álcalis/química , Microbiología del Suelo , Salinidad
4.
Inflamm Res ; 71(5-6): 641-652, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35347345

RESUMEN

OBJECT: Phosphatidylserine-containing liposomes (PSLs) can mimic the immunomodulatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. Sodium butyrate, an antiinflammatory short-chain fatty acid, is known to facilitate the M2 polarization of macrophages. This study aimed to investigate the effect of sodium butyrate on PSLs-induced macrophage polarization. METHODS: PSLs physical properties and cellular uptake tests, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry analysis were performed to assess the polarization-related indicators of M1/M2 macrophages. RESULTS: The results showed that sodium butyrate did not affect the size and cellular uptake of PSLs. For M1 macrophage polarization, sodium butyrate significantly intensified the antiinflammatory function of PSLs, inhibiting LPS-induced proinflammatory genes expression, cytokines and enzyme release (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, and inducible nitric oxide synthase), as well as CD86 (M1 marker) expression. In addition to the enhancing effect of antiinflammation, sodium butyrate also promoted PSL-induced M2 macrophages polarization, especially elevated thymus and activation-regulated chemokine (TARC) and arginase-1 (Arg-1) enzyme levels which are involved in tissue repair. CONCLUSION: Sodium butyrate enhanced antiinflammatory properties and M2-polarization inducing effect of PSLs. Therefore, sodium butyrate may represent a novel approach to enhance PSL-induced macrophage polarization.


Asunto(s)
Liposomas , Fosfatidilserinas , Antiinflamatorios/farmacología , Ácido Butírico/metabolismo , Ácido Butírico/farmacología , Liposomas/metabolismo , Liposomas/farmacología , Activación de Macrófagos , Macrófagos , Fosfatidilserinas/metabolismo , Fosfatidilserinas/farmacología
5.
Microb Cell Fact ; 21(1): 88, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35578339

RESUMEN

BACKGROUND: The extracellular vesicles (EVs) traffic constitutes an essential pathway of cellular communication. And the molecules in EVs produced by procaryotes help in maintaining homeostasis, addressing microbial imbalance and infections, and regulating the immune system. Despite the fact that Clostridium butyricum (C. butyricum) is commonly used for treating ulcerative colitis (UC), the potential role of C. butyricum-secreted EVs in commensals-host crosstalk remains unclear. RESULTS: Here, we performed flow cytometry, western blot, immunohistochemistry and 16S rRNA analysis to explore the role of C. butyricum-derived EVs on macrophage polarization and gut microbiota composition in a dextran sulfate sodium (DSS)-induced UC mouse model. The antibiotic cocktail-induced microbiome depletion and faecal transplantations were used to further investigate the mechanisms by which EVs regulate macrophage balance. Our findings showed that C. butyricum-derived EVs improved the remission of murine colitis and polarized the transformation of macrophages to the M2 type. Furthermore, C. butyricum-derived EVs restored gut dysbiosis and altered the relative abundance of Helicobacter, Escherichia-Shigella, Lactobacillus, Akkermansia and Bacteroides, which, in turn, faecal transplantations from EVs-treated mice relieved the symptoms of UC and improved the impact of EVs on the reprogramming of the M2 macrophages. CONCLUSION: C. butyricum-derived EVs could protect against DSS-induced colitis by regulating the repolarization of M2 macrophages and remodelling the composition of gut microbiota, suggesting the potential efficacy of EVs from commensal and probiotic Clostridium species against UC.


Asunto(s)
Clostridium butyricum , Colitis Ulcerosa , Colitis , Vesículas Extracelulares , Microbioma Gastrointestinal , Animales , Clostridium butyricum/genética , Colitis/inducido químicamente , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/terapia , Colon , Citocinas , Sulfato de Dextran/efectos adversos , Sulfato de Dextran/metabolismo , Modelos Animales de Enfermedad , Macrófagos , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genética
6.
Gut ; 70(10): 1857-1871, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33239342

RESUMEN

OBJECTIVE: NFκB is the key modulator in inflammatory disorders. However, the key regulators that activate, fine-tune or shut off NFκB activity in inflammatory conditions are poorly understood. In this study, we aim to investigate the roles that NFκB-specific long non-coding RNAs (lncRNAs) play in regulating inflammatory networks. DESIGN: Using the first genetic-screen to identify NFκB-specific lncRNAs, we performed RNA-seq from the p65-/- and Ikkß-/- mouse embryonic fibroblasts and report the identification of an evolutionary conserved lncRNA designated mNAIL (mice) or hNAIL (human). hNAIL is upregulated in human inflammatory disorders, including UC. We generated mNAILΔNFκB mice, wherein deletion of two NFκB sites in the proximal promoter of mNAIL abolishes its induction, to study its function in colitis. RESULTS: NAIL regulates inflammation via sequestering and inactivating Wip1, a known negative regulator of proinflammatory p38 kinase and NFκB subunit p65. Wip1 inactivation leads to coordinated activation of p38 and covalent modifications of NFκB, essential for its genome-wide occupancy on specific targets. NAIL enables an orchestrated response for p38 and NFκB coactivation that leads to differentiation of precursor cells into immature myeloid cells in bone marrow, recruitment of macrophages to inflamed area and expression of inflammatory genes in colitis. CONCLUSION: NAIL directly regulates initiation and progression of colitis and its expression is highly correlated with NFκB activity which makes it a perfect candidate to serve as a biomarker and a therapeutic target for IBD and other inflammation-associated diseases.


Asunto(s)
Colitis/genética , Colitis/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción ReIA/metabolismo , Animales , Biomarcadores/metabolismo , Progresión de la Enfermedad , Fibroblastos/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Ratones , Proteína Fosfatasa 2C/metabolismo
7.
Ecotoxicol Environ Saf ; 207: 111287, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32931967

RESUMEN

Coming along with high water reuse in sustainable and intensive recirculating aquaculture systems (RASs), the waste products of fish in rearing water is continuously accumulated. Nitrate, the final product of biological nitrification processes, which may cause aquatic toxicity to fish in different degrees when exposed for a long time. Therefore, the present study was conducted to evaluate the impact of chronic nitrate exposure on intestinal morphology, immune status, barrier function, and microbiota of juvenile turbot. For that, groups of juvenile turbot were exposed to 0 (control check, CK), 50 (low nitrate, L), 200 (medium nitrate, M), and 400 (high nitrate, H) mg L-1 nitrate-N in small-sized recirculating aquaculture systems. After the 60-day experiment period, we found that exposure to a high concentration of nitrate-N caused obvious pathological damages to the intestine; for instance, atrophy of intestinal microvilli and necrosis in the lamina propria. Quantitative real-time PCR analysis revealed a significant downregulation of the barrier forming tight junction genes like occludin, claudin-like etc. under H treatment (P < 0.05). Intestinal MUC-2 expression also decreased significantly in the nitrate treatment groups compared to that in the control (P < 0.05). Additionally, the expression of HSP70 and HSP90 heat-shock proteins, toll-like receptor-3 (TLR-3), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) significantly increased (P < 0.05), whereas that of transforming growth factor-ß (TGF-ß), lysozyme (LYS), and insulin-like growth factor-I (IGF-I) significantly decreased with H treatment (P < 0.05). The results also revealed that intestinal microbial community was changed following nitrate exposure and could alter the α-diversity and ß-diversity. Specifically, the proportion of intrinsic flora decreased, whereas that of the potential pathogens significantly increased with M and H treatments (P < 0.05). In conclusion, chronic nitrate exposure could weaken the barrier function and disturb the composition of intestinal microbiota in marine teleosts, thereby harming their health condition.


Asunto(s)
Peces Planos/crecimiento & desarrollo , Microbioma Gastrointestinal/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Nitratos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , ADN Bacteriano/genética , Relación Dosis-Respuesta a Droga , Peces Planos/microbiología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Intestinos/microbiología
8.
Pharmacol Res ; 155: 104726, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32109579

RESUMEN

The telomerase holoenzyme, which has a highly conserved role in maintaining telomere length, has long been regarded as a high-profile target in cancer therapy due to the high dependency of the majority of cancer cells on constitutive and elevated telomerase activity for sustained proliferation and immortality. In this review, we present the salient findings in the telomerase field with special focus on the association of telomerase with inflammation and cancer. The elucidation of extra-telomeric roles of telomerase in inflammation, reactive oxygen species (ROS) generation, and cancer development further complicated the design of anti-telomerase therapy. Of note, the discovery of the unique mechanism that underlies reactivation of the dormant telomerase reverse transcriptase TERT promoter in somatic cells not only enhanced our understanding of the critical role of TERT in carcinogenesis but also opens up new intervention ideas that enable the differential targeting of cancer cells only. Despite significant effort invested in developing telomerase-targeted therapeutics, devising efficacious cancer-specific telomerase/TERT inhibitors remains an uphill task. The latest discoveries of the telomere-independent functionalities of telomerase in inflammation and cancer can help illuminate the path of developing specific anti-telomerase/TERT therapeutics against cancer cells.


Asunto(s)
Inflamación/enzimología , Neoplasias/enzimología , Telomerasa/metabolismo , Animales , Humanos , Estrés Oxidativo
9.
Molecules ; 25(11)2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32532146

RESUMEN

Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the discs. The coated discs were hydrated before cell culture was added. The shape of the hydrated phospholipids varied with the concentration of loaded phospholipids: a perforated layer (0.1 mM), tubules and spheres (1 mM), and spheres (10 mM). RAW 264.7 cells exhibited different morphologies, depending on the concentration of phospholipids. On the coated discs, the gene expression and protein release of TGF-ß1, VEGF, Arg-1, and TNF-α were downregulated, especially with 10 mM phospholipids. The stimulation of mRNA expression and the protein release of those genes by IL-4 and LPS were also disturbed on the phospholipid-coated discs. In conclusion, the polarization of RAW 264.7 cells was prevented by hydrated phospholipids on Ti discs.


Asunto(s)
Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Fosfolípidos/farmacología , Titanio/química , Animales , Adhesión Celular , Proliferación Celular , Células Cultivadas , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Fosfolípidos/química , Propiedades de Superficie , Factor de Crecimiento Transformador beta1/metabolismo
10.
J Biol Chem ; 293(48): 18646-18654, 2018 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-30315105

RESUMEN

Cancer stem cells (CSCs) have been reported in a variety of cancers. SRY-box 2 (SOX2) is a member of the SOX family of transcription factors and has been shown to play a critical role in maintaining the functions of CSCs and promoting tumor initiation. However, the underlying mechanisms for the transcriptional regulation of the SOX2 gene in CSCs are unclear. In this study, using in silico and experimental approaches, we identified transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA-type transcription factor, as a critical transcriptional regulator that represses SOX2 expression and thereby suppresses cancer stemness and tumorigenesis. Mechanistically, TRPS1 repressed SOX2 expression by directly targeting the consensus GATA-binding element in the SOX2 promoter as elucidated by ChIP and luciferase reporter assays. Of note, in vitro mammosphere formation assays in culture and in vivo xenograft tumor initiation experiments in mouse models revealed that TRPS1-mediated repression of SOX2 expression suppresses CSC functions and tumor initiation. Taken together, our study provides detailed mechanistic insights into CSC functions and tumor initiation by the TRPS1-SOX2 axis.


Asunto(s)
Carcinogénesis , Proteínas de Unión al ADN/metabolismo , Células Madre Neoplásicas/patología , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Línea Celular , Inmunoprecipitación de Cromatina , Proteínas de Unión al ADN/genética , Silenciador del Gen , Xenoinjertos , Humanos , Ratones , Células Madre Neoplásicas/metabolismo , Regiones Promotoras Genéticas , Proteínas Represoras , Factores de Transcripción SOXB1/genética , Factores de Transcripción/genética
11.
Fish Shellfish Immunol ; 86: 1169-1176, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30599254

RESUMEN

Land-based recirculating aquaculture systems (RAS) are widely utilized for turbot (Scophthalmus maximus) culture. Flow velocity in the tank is essential to maintain water quality, conservation of energy and fish welfare. However, little is known about how turbot respond to different velocities in the long term. In this study, water quality was kept constant, allowing the effect of flow velocity on the feeding intake, growth, plasma biochemical indexes, innate (non-specific) immunity and immune-related stress gene expressions in the skin to be examined in isolation in RAS. Turbot (average body length 20.10 cm) were reared for 60 days in RAS under three velocities, 0.06 m s-1, 0.18 m s-1, and 0.36 m s-1, corresponding to approximately 0.3 body length per second (bl s-1), 0.9 bl s-1 and 1.8 bl s-1, respectively. The results showed that at velocities of 0.36 m s-1 (1.8 bl s-1), juvenile turbot were subject to stress accompanied by a reduced growth rate. A velocity of 0.36 m s-1 was also found to significantly reduce SOD and GSH activity, and the concentration of total protein in plasma, while concentrations of urea nitrogen (BUN) and total bilirubin (TBIL) increased. There was an up-regulation of cathepsin D and lysozyme (LZM) in the skin at the highest velocity, implying the activation of stress and immune responses. At the medium velocity of 0.18 m s-1 (0.9 bl s-1), turbot increased their feed intake, obtained an elevated special growth rate (SGR), and exhibited significantly higher AKP and ACP activity in plasma. Overall, the results suggest that excessively high velocities are a stressor for turbot inducing an immune response in the skin, which is sensitive to environmental changes. A velocity of approximately 0.9 bl s-1 is suggested to promote growth and obtain better innate immunity of cultured turbot.


Asunto(s)
Acuicultura/métodos , Peces Planos/crecimiento & desarrollo , Peces Planos/inmunología , Movimientos del Agua , Animales , Inmunidad Innata , Piel/inmunología , Estrés Fisiológico/fisiología
12.
Fish Shellfish Immunol ; 90: 328-337, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31071463

RESUMEN

Light is a key environmental factor that synchronizes various life stages from embryo development to sexual maturation in fish. For turbot, light spectra have the most influence at the larval and juvenile stages. In the current study, differences in the development of embryos and the performance of newly hatched turbot larvae exposed to five different spectra: full spectrum (LDF), blue (LDB, peak at 450 nm), green (LDG, peak at 533 nm), orange (LDO, peak at 595 nm) and red (LDR, peak at 629 nm), were examined. At 62.8 h post fertilization, a higher number of embryos exposed to short-wavelengths (LDG and LDB) had developed a heartbeat in comparison with embryos exposed to other wavelengths. Larvae exposed to the green spectrum had higher malformation rates than larvae exposed to the other spectra, indicating that larvae exposed to green light may have significantly reduced survival rates. The results of non-specific immunity parameters showed that the mRNA expression levels of cathepsin D (CTSD), cathepsin F (CTSF), catalase (CAT) and metallothionein (MT) in larvae exposed to LDB were significantly higher than those exposed to other spectra, but CAT activity in larvae exposed to LDB was significantly lower than larvae exposed to the other spectra. There was no significant difference in MT activity in larvae exposed to the five different spectra. The mRNA expression level of lysozyme (LZM) in larvae exposed to LDR was significantly higher than other spectra, while there was no significant difference in LZM activity observed in larvae exposed to LDR, LDG, LDB and LDF. The difference of the enzyme activity of total superoxide dismutase (T-SOD) was not significant among larvae exposed to the five spectra. mRNA expression of the heat shock protein 70 (HSP70) was significantly higher in newly hatched larvae exposed to LDB, LDR and LDG, indicating that larvae exposed to LDB, LDG and LDR exhibited a stress response. The mRNA expression level of the insulin-like growth factor-1 (IGF-1) and growth parameters in the newly hatched larvae exposed to the different spectra were not significantly different. The results of the present study indicate that LDO and LDF should be used for embryo incubation and newly hatched larvae when rearing turbot. This study provides a theoretical basis for optimizing the incubation light environment for fertilized turbot eggs, promoting immunity and reducing stress responses in newly hatched larvae.


Asunto(s)
Embrión no Mamífero/efectos de la radiación , Desarrollo Embrionario/efectos de la radiación , Peces Planos/crecimiento & desarrollo , Luz , Animales , Antioxidantes/metabolismo , Antioxidantes/efectos de la radiación , Peces Planos/genética , Peces Planos/metabolismo , Expresión Génica/efectos de la radiación , Inmunidad Innata/efectos de la radiación
13.
J Cell Physiol ; 233(5): 3892-3900, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28796300

RESUMEN

Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease.


Asunto(s)
Apelina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Enfermedades Renales/terapia , Daño por Reperfusión/terapia , Animales , Humanos , Receptores Acoplados a Proteínas G/efectos de los fármacos , Calcificación Vascular/prevención & control
14.
J Cell Physiol ; 233(10): 6839-6850, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29691838

RESUMEN

Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI. Autophagy flux induced by apelin-13 was inhibited by NAC and catalase but not hydroxychloroquine (HCQ). NAC, catalase, and DPI prevented apelin-13 induced ICAM-1 expression in HUVECs. Rapamycin enhanced MCs-HUVECs adhesion that was reversed by NAC, catalase, and DPI. Down-regulation of beclin1 and LC3 by siRNA blocked MCs-HUVECs adhesion. Apelin-13 induced atherosclerotic plaque and increased NOX4, LC3-II/I expression in ApoE-/-(HFD) mouse model. Our results demonstrated that apelin-13 induced MCs-HUVECs adhesion via a ROS-autophagy pathway.


Asunto(s)
Autofagia/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Monocitos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Autofagia/fisiología , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ratones Noqueados , Monocitos/metabolismo , NADPH Oxidasas/efectos de los fármacos , NADPH Oxidasas/metabolismo , Transducción de Señal/efectos de los fármacos , Venas Umbilicales/efectos de los fármacos , Venas Umbilicales/metabolismo
15.
Breast Cancer Res ; 20(1): 83, 2018 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-30071870

RESUMEN

BACKGROUND: Although numerous studies have reported that tricho-rhino-phalangeal syndrome type I (TRPS1) protein, the only reported atypical GATA transcription factor, is overexpressed in various carcinomas, the underlying mechanism(s) by which it contributes to cancer remain unknown. METHODS: Both overexpression and knockdown of TRPS1 assays were performed to examine the effect of TRPS1 on histone deacetylase 2 (HDAC2) protein level and luminal breast cancer cell proliferation. Also, RT-qRCR, luciferase reporter assay and RNA-sequencing were used for transcription detection. Chromatin immunoprecipitation (ChIP) using H4K16ac antibody in conjunction with qPCR was used for determining H4K16ac levels in targeted genes. Furthermore, in vitro cell proliferation assay and in vivo tumor xenografts were used to detect the effect of TRPS1 on tumor growth. RESULTS: We found that TRPS1 scaffolding recruits and enhances interaction between USP4 and HDAC2 leading to HDAC2 de-ubiquitination and H4K16 deacetylation. We detected repression of a set of cellular growth-related genes by the TRPS1-USP4-HDAC2 axis indicating it is essential in tumor growth. In vitro and in vivo experiments confirmed that silencing TRPS1 reduced tumor growth, whereas overexpression of HDAC2 restored tumor growth. CONCLUSION: Our study deciphered the TRPS1-USP4-HDAC2 axis as a novel mechanism that contributes to tumor growth. Significantly, our results revealed the scaffolding function of TPRS1 in USP4-directed HDAC2 de-ubiquitination and provided new mechanistic insights into the crosstalk between TRPS1, ubiquitin, and histone modification systems leading to tumor growth.


Asunto(s)
Neoplasias de la Mama/patología , Carcinogénesis/patología , Proteínas de Unión al ADN/metabolismo , Histona Desacetilasa 2/metabolismo , Factores de Transcripción/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Animales , Neoplasias de la Mama/genética , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HEK293 , Histona Desacetilasa 2/genética , Histonas/metabolismo , Humanos , Ratones , Ratones Desnudos , Unión Proteica , Dominios y Motivos de Interacción de Proteínas/genética , Proteínas Represoras , Factores de Transcripción/genética , Ubiquitinación , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Clin Lab ; 63(9): 1447-1456, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28879720

RESUMEN

BACKGROUND: The long non-coding RNAs (lncRNAs) are significantly altered in an expanding list of malignant neoplasms, suggesting that they might be popularized as potential biomarkers for cancer detection. This study sought to validate the diagnostic efficacy of lncRNA expression signature(s) as potential biomarker(s) for non-small cell lung cancer (NSCLC) diagnosis. METHODS: We conducted the online databases search for all eligible studies. A quantitative meta-analysis was performed using Stata 12.0 and Meta-Disc 1.4 statistical programs. Sensitivity analysis and a meta-regression test were applied to deeply trace the underlying heterogeneity sources. RESULTS: Eight cohorts comprised 775 NSCLC patients and 630 matched controls were included. Our data manifested that lncRNA expression profiling harbored a pooled sensitivity of 0.77 (95% CI: 0.71 - 0.82) and specificity of 0.86 (95% CI: 0.80 - 0.90) in discriminating NSCLC cases from cancer-free individuals, along with an AUC (area under the curve) value of 0.88. Further subgroup analysis revealed that paralleled testing of lncRNAs (sensitivity, specificity, and AUC of 0.90, 0.80 and 0.96, respectively) substantially strengthened the diagnostic efficacy as compared with the single testing pattern (sensitivity, specificity, and AUC of 0.71, 0.77 and 0.82, respectively). Other stratified analysis of ethnicity, histology type, and test matrix also presented robust results. CONCLUSIONS: Altogether, our results indicate that lncRNA expression signature(s) might be applicable as complementary biomarker(s) for the identification of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor , Estudios de Casos y Controles , Humanos , Curva ROC
17.
Food Chem Toxicol ; 183: 114307, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052408

RESUMEN

Uric acid (UA) is the final metabolite of purines in the liver that can cause hyperuricemia at high levels. The kidneys are the main excretory organs for UA. The excessive accumulation of UA in the kidneys causes the development of hyperuricemia that often leads to renal injury. Eupatilin (Eup) is a flavonoid natural product that possesses various pharmacological properties such as antioxidant, anti-cancer, and anti-inflammatory. We were interested in exploring the potential role of Eup in lowering UA and nephroprotective. We initially investigated the effects of Eup on xanthin oxidase (XOD) activity in vitro, followed by investigating its ability to lower UA levels, anti-inflammatory effects, nephroprotective effects, and the underlying mechanisms using hyperuricemia rats sustained at high UA level. The results showed that Eup had an inhibitory effect on XOD activity in vitro and significantly reduced serum UA, creatinine, BUN, IL-1ß and IL-6 levels in hyperuricemic rats, ameliorating inflammation, renal oxidative stress and pathological injury. Furthermore, Eup inhibited ADA and XOD enzyme activities in the liver and serum and modulated GLUT9, URAT1 and ABCG2 protein expression in the kidneys and ileum. Our findings provide a scientific basis for suggesting Eup as an option for a potential treatment for hyperuricemia.


Asunto(s)
Hiperuricemia , Ratas , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Xantina Oxidasa , Riñón , Flavonoides/farmacología , Flavonoides/uso terapéutico , Ácido Úrico/metabolismo , Antiinflamatorios/farmacología
18.
Artículo en Inglés | MEDLINE | ID: mdl-38007980

RESUMEN

Fish body color changes play vital roles in adapting to ecological light environment and influencing market value. However, the initial mechanisms governing the changes remain unknown. Here, we scrutinized the impact of light spectrum on turbot (Scophthalmus maximus) body coloration, exposing them to red, blue, and full light spectra from embryo to 90 days post hatch. Transcriptome and quantitative real-time PCR (qRT-PCR) analyses were employed to elucidate underlying biological processes. The results showed that red light induced dimorphism in turbot juvenile skin pigmentation: some exhibited black coloration (Red_Black_Surface, R_B_S), while others displayed lighter skin (Red_White_Bottom, R_W_B), with red light leading to reduced skin lightness (L*) and body weight, particularly in R_B_S group. Transcriptomic and qRT-PCR analyses showcased upregulated gene expressions related to melanin synthesis in R_B_S individuals, notably tyrosinase (tyr), tyrosinase-related protein 1 (tyrp1), and dopachrome tautomerase (dct), alongside solute carrier family 24 member 5 (slc24a5) and oculocutaneous albinism type II (oca2) as pivotal regulators. Nervous system emerged as a critical mediator in spectral environment-driven color regulation. N-methyl d-aspartate (NMDA) glutamate receptor, and calcium signaling pathway emerged as pivotal links intertwining spectral conditions, neural signal transduction, and color regulation. The individual differences in NMDA glutamate receptor expression and subsequent neural excitability seemed responsible for dichromatic body coloration in red light-expose juveniles. This study provides new insights into the comprehending of fish adaptation to environment and methods for fish body color regulation and could potentially help enhance the economic benefit of fish farming industry.


Asunto(s)
Albinismo Oculocutáneo , Peces Planos , Transcriptoma , Animales , Monofenol Monooxigenasa/genética , N-Metilaspartato/genética , Perfilación de la Expresión Génica , Pigmentación de la Piel/genética , Receptores de Glutamato/genética
19.
Heliyon ; 10(16): e35424, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220963

RESUMEN

Background and aims: In all age, FoShou as a Chinese medicinal herb has been active in various kinds of Traditional Chinese medicine formula to treating diabetes. Hesperidin (HES), the main monomeric component of FoShou, has been extensively investigated for interventions with pathogenic mechanism of diabetes as well as subsequent treatment of associated complications. Islet ß-cells have an essential effect on dynamically regulating blood sugar. Functional abnormalities in these cells and their death are strongly associated with the onset of diabetes. Therefore, induction of islet endocrine cell lineage re-editing for damaged ßcell replenishment would be a promising therapeutic tool. Previously, it has been found that HES can protect islet ß-cells in vivo, But, the regenerative function of HES in islet ß cells and its role in promoting differential non-ß cells transdifferentiation into ß cells and cell fate rewriting associated mechanisms remain unclear.This work focused on investigating whether HES can induce islet α cells transdifferentiation into ß cells for achieving damaged ß cell regeneration and the causes and possible mechanisms involved in the process. Materials and methods: In brief, 60 mg/kg/d streptozotocin (STZ) was administered intraperitoneally in each male C57bL/6J mouse raised by the high-sugar and high-fat diet (HFD) to create a diabetic mouse model with severe ß-cell damage. After 28 consecutive days of HES treatment (160 mg/kg; 320 mg/kg; once daily, as appropriate). Tracing the dynamics of α as well as ß cell transformation, together with ß cells growth and apoptosis levels during treatment by cell lineage tracing. The self-enforcing transcriptional network on which the cell lineage is based is used as a clue to explore the underlying mechanisms. Guangdong Pharmaceutical University's Animal Experiment Ethics Committee (GDPulac2019180) approved all animal experiments. Results: Localization by cell lineage we find that transdifferentiated newborn ß-cells derived from α cells appeared in the islet endocrine cell mass of DM mice under HES'action. Compared to the model group, expressed by Tunel staining and CXCL10 levels the overall apoptosis rate of ß-cells of the pancreas were reduced,the inflammatory infiltration feedback from HE staining were lower.Ki-67 positive cells showed enhanced ß-cell proliferation. Decreased HbA1c and blood glucose contents, elevated C-Peptide and insulin contents which respond to ability of nascent beta cells. Also upregulated the mRNA levels of MafA, Ngn3, PDX-1, Pax4 and Arx. Moreover, increased the expression of TGR5/cAMP-CREB/GLP-1 in mouse intestinal tissues and GLP-1/GLP-1R and cAMP-CREB/IRS2/PDX-1 in pancreatic tissues. Conclusions: HES directly affects ß-cells, apart from being anti-apoptotic and reducing inflammatory infiltration. HES promotes GLP-1 release by intestinal L cells by activating the TGR5 receptor in DM mouse and regulating its response element CREB signaling. GLP-1 then uses the GLP-1/GLP-1R system to act on IRS2, IRS2 as a port to influence α precursor cells to express PDX-1, with the mobilization of Pax4 strong expression than Arx so that α cell lineage is finally reversed for achieving ß cell endogenous proliferation.

20.
Front Microbiol ; 15: 1433910, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234549

RESUMEN

The gut microbiota is widely regarded as a "metabolic organ" that could generate myriad metabolites to regulate human metabolism. As the microbiota metabolites, bile acids (BAs) have recently been identified as the critical endocrine molecules that mediate the cross-talk between the host and intestinal microbiota. This study provided a comprehensive insight into the gut microbiota and BA research through bibliometric analysis from 2003 to 2022. The publications on this subject showed a dramatic upward trend. Although the USA and China have produced the most publications, the USA plays a dominant role in this expanding field. Specifically, the University of Copenhagen was the most productive institution. Key research hotspots are the gut-liver axis, short-chain fatty acids (SCFAs), cardiovascular disease (CVD), colorectal cancer (CRC), and the farnesoid x receptor (FXR). The molecular mechanisms and potential applications of the gut microbiota and BAs in cardiometabolic disorders and gastrointestinal cancers have significant potential for further research.

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