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1.
Nat Commun ; 15(1): 5985, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013850

RESUMO

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.


Assuntos
Envelhecimento , Aneurisma Aórtico , Dissecção Aórtica , Senescência Celular , MicroRNAs , Músculo Liso Vascular , Quinase de Cadeia Leve de Miosina , Transdução de Sinais , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Quinase de Cadeia Leve de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Masculino , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Dissecção Aórtica/metabolismo , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Miócitos de Músculo Liso/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Fator de Crescimento Transformador beta/metabolismo , Modelos Animais de Doenças , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Angiotensina II/metabolismo , Proteínas de Ligação ao Cálcio
2.
MedComm (2020) ; 5(7): e632, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988491

RESUMO

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

3.
Acta Pharm Sin B ; 14(7): 2977-2991, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027231

RESUMO

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

4.
Sci Rep ; 14(1): 16455, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014184

RESUMO

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.


Assuntos
Imagem de Tensor de Difusão , Humanos , Masculino , Recém-Nascido , Feminino , Imagem de Tensor de Difusão/métodos , Estudos Prospectivos , Hemorragia Cerebral/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/etiologia , Lactente , Hemorragia Cerebral Intraventricular/diagnóstico por imagem , Idade Gestacional , Desenvolvimento Infantil , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia
6.
BMC Oral Health ; 24(1): 629, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807098

RESUMO

BACKGROUND: In orthodontics, anterior open bite is a common malocclusion that recurs frequently. Because the causes of anterior open bite are so varied, medical professionals must create customized treatment programs for each patient based on their unique etiology. Through the lowering of the posterior teeth, closure of the anterior teeth gap, and cooperation with intermaxillary traction, the treatment plan outlined in this case study sought to achieve a stable occlusion. CASE PRESENTATION: This case report aims to describe an orthodontic camouflage treatment of a 15-year-old female patient with anterior open bite, arch width discrepancy and a history of temporomandibular joint disorder. The patient was treated with intermaxillary vertical elastics and the multiple edgewise arch wire (MEAW) approach. A satisfactory occlusion with a neutral molar relationship was attained after 29 months of orthodontic therapy. The condylography recording showed that this patient's occlusion tended to be more stable both before and after our treatment. The purpose of this case study is to provide an overview of an orthodontic camouflage treatment for a female patient, who had a history of temporomandibular joint disease, anterior open bite, and arch width disparity. CONCLUSIONS: Our results demonstrated that more attention should be paid to levelling the occlusal plane, intrusion of the molars, decompression of temporomandibular joints and the etiology factors of malocclusion during the orthodontic period for those patients with anterior open bite.


Assuntos
Mordida Aberta , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Adolescente , Mordida Aberta/terapia , Transtornos da Articulação Temporomandibular/terapia , Ortodontia Corretiva/métodos , Cefalometria , Planejamento de Assistência ao Paciente
7.
Animals (Basel) ; 14(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38731354

RESUMO

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (p < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (p < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5-7 years (p < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (p < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (p < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (p < 0.05). Interestingly, the skin's antioxidant capacity and oxidative damage exhibited significant positive and negative correlations with the population of active secondary hair follicles (p < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

8.
Front Immunol ; 15: 1402468, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799471

RESUMO

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.


Assuntos
Exossomos , Macrófagos , Isquemia Miocárdica , Exossomos/metabolismo , Exossomos/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/metabolismo , Animais
9.
Animals (Basel) ; 14(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612237

RESUMO

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

10.
Mediators Inflamm ; 2024: 9078794, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590775

RESUMO

Background: Acute pancreatitis (AP) is a clinically frequent acute abdominal condition, which refers to an inflammatory response syndrome of edema, bleeding, and even necrosis caused by abnormal activation of the pancreas's own digestive enzymes. Intestinal damage can occur early in the course of AP and is manifested by impaired intestinal mucosal barrier function, and inflammatory reactions of the intestinal mucosa, among other factors. It can cause translocation of intestinal bacteria and endotoxins, further aggravating the condition of AP. Therefore, actively protecting the intestinal mucosal barrier, controlling the progression of intestinal inflammation, and improving intestinal dynamics in the early stages of AP play an important role in enhancing the prognosis of AP. Methods: The viability and apoptosis of RAW264.7 cells treated with Esculentoside A (EsA) and/or lipopolysaccharide were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The expression of apoptosis-related proteins and NF-κB signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-α and IL-6 secretion. Results: In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-α and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-κB signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of IκBα. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of IκBα in the intestinal tissues of the rat AP model and promoting the apoptosis of inflammatory cells in the intestinal mucosa in vivo experiments, while improving the pathological outcome of the pancreatic and intestinal tissues. Conclusion: Our results suggest that EsA can reduce intestinal inflammation in the rat AP model and that EsA may be a candidate for treating intestinal inflammation in AP and further arresting AP progression.


Assuntos
NF-kappa B , Ácido Oleanólico/análogos & derivados , Pancreatite , Saponinas , Ratos , Animais , NF-kappa B/metabolismo , Pancreatite/metabolismo , Inibidor de NF-kappaB alfa , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Doença Aguda , Inflamação/tratamento farmacológico
11.
Cell Prolif ; : e13631, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453465

RESUMO

Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization and difficulty in formation of cardiac chamber were yet to be overcome. We established a new method for robust generation of COs, via combination of methodologies of hiPSC-derived vascular spheres and directly differentiated cardiomyocytes from hiPSCs, and investigated the potential application of human COs in cardiac injury modelling and drug evaluation. The human COs we built displayed a vascularized and chamber-like structure, and hence were named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single-cell transcriptomics identified a total of six cell types in the vcCOs, including cardiomyocytes, cardiac precursor cells, endothelial cells, fibroblasts, etc. We successfully recaptured the processes of cardiac injury and fibrosis in vivo on vcCOs, and showed that the FDA-approved medication captopril significantly attenuated cardiac injury-induced fibrosis and functional disorders. In addition, the human vcCOs exhibited an obvious drug toxicity reaction to doxorubicin in a dose-dependent manner. We developed a three-step method for robust generation of chamber-like and vascularized complex vcCOs, and our data suggested that vcCOs might become a useful model for understanding pathophysiological mechanisms of cardiovascular diseases, developing intervention strategies and screening drugs.

12.
Sci Rep ; 14(1): 5709, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459090

RESUMO

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.


Assuntos
Doenças do Prematuro , Recém-Nascido Prematuro , Lactente , Humanos , Recém-Nascido , Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética , Doenças do Prematuro/diagnóstico por imagem
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124064, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38428215

RESUMO

As two of important highly reactive species / nitrogen species, hypochloric acid (HClO) and peroxynitrite (ONOO-) are involved in various pathological and physiological processes, which are important factors that affect and reflect the functional state of lysosome. Nevertheless, many of their roles are still indefinite because of lack of suitable analytical methods for HClO and ONOO- detection in lysosome. Herein, we designed a lysosome-targeted probe to monitor HClO and ONOO-, which was a hydrid of the benzothiazole derivative, methyl thioether (HClO recognition site) and morpholino hydrazone (ONOO- recognition and lysosome target site). The probe exhibited high sensitivity, good selectivity and fast response toward HClO and ONOO- without spectral crosstalk, and can be employed for quantitative monitoring HClO and ONOO- with LOD of 63 and 83 nM, respectively. In addition, the dual-site probe was lysosome targetable and could be used for detection of HClO and ONOO- in living cells. Furthermore, the excellent behavior made it was suitable for imaging of HClO and ONOO- in zebrafish. Thus, the present probe provides a potent tool for distinguishing monitoring HClO and ONOO- and exploring the role of HClO and ONOO- in biological systems.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Humanos , Animais , Lisossomos , Ácido Peroxinitroso , Células HeLa , Ácido Hipocloroso
15.
Pediatr Radiol ; 54(5): 776-786, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38321237

RESUMO

BACKGROUND: Intraventricular haemorrhage (IVH) often arises as a cerebral complication directly related to preterm birth. The impaired autoregulation of cerebral blood flow is closely associated with IVH in preterm neonates. Three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) is a noninvasive magnetic resonance imaging (MRI) technique used for evaluating cerebral perfusion. OBJECTIVE: This study aimed to compare cerebral blood flow values among three distinct groups using 3D-pCASL: preterm neonates with and without IVH and preterm neonates at term-equivalent age. MATERIALS AND METHODS: A total of 101 preterm neonates who underwent conventional MRI and 3D-pCASL were included in this study. These neonates were categorised into three groups: 12 preterm neonates with IVH, 52 preterm neonates without IVH, and 37 healthy neonates at term-equivalent age. Cerebral blood flow measurements were obtained from six brain regions of interest (ROIs)-the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus-in the right and left hemispheres. RESULTS: The cerebral blood flow values measured in all ROIs of preterm neonates with IVH were significantly lower than those of neonates at term-equivalent age (all P<0.05). Additionally, the cerebral blood flow in the temporal lobe was lower in preterm neonates without IVH than in neonates at term-equivalent age (16.87±5.01 vs. 19.76±5.47 ml/100 g/min, P=0.012). Furthermore, a noteworthy positive correlation was observed between post-menstrual age and cerebral blood flow in the temporal lobe (P=0.037), basal ganglia (P=0.010), and thalamus (P=0.010). CONCLUSION: The quantitative cerebral blood flow values, as measured by 3D-pCASL, highlighted that preterm neonates with IVH had decreased cerebral perfusion. This finding underscores the potential of 3D-pCASL as a technique for evaluating the developmental aspects of the brain in preterm neonates.


Assuntos
Circulação Cerebrovascular , Imageamento Tridimensional , Recém-Nascido Prematuro , Marcadores de Spin , Humanos , Recém-Nascido , Masculino , Feminino , Circulação Cerebrovascular/fisiologia , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/fisiopatologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia
16.
Adv Sci (Weinh) ; 11(13): e2306685, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286660

RESUMO

Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition-induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet-induced insulin-resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF-κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Resistência à Insulina/genética , Macrófagos/metabolismo , Obesidade/metabolismo
18.
J Nanobiotechnology ; 21(1): 465, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049882

RESUMO

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Humanos , Feminino , Neoplasias da Mama/terapia , Verde de Indocianina/química , Fototerapia , Nanopartículas/química , Homeostase , Linhagem Celular Tumoral
19.
Opt Express ; 31(24): 40781-40791, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041370

RESUMO

We demonstrate the generation of both continuous-wave (CW) and Q-switched cylindrical vector beams (CVBs) from a mid-infrared Er3+-doped ZBLAN (Er:ZBLAN) fiber laser at ∼ 2.8 µm. A customized S-waveplate is incorporated as the intracavity mode converter to achieve the mid-infrared CVBs. Switchable modes of CVBs between the radially and azimuthally polarized beam can be realized easily by manipulating the cavity conditions. A maximum output power of ∼250 mW is achieved for the CW CVBs. In the short-pulsed CVBs operation regime, both the active and passive Q-switching modes are realized with a pulse duration of hundreds of nanoseconds. The proposed mid-infrared cylindrical vector lasers can have significant potential for applications in biomedicine, optical trapping, material processing and optical communication.

20.
Animals (Basel) ; 13(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38003137

RESUMO

The objective of this study was to investigate the effects of fasted live-weight gain during the cashmere non-growing period on cashmere production performance and secondary hair follicle activity, to provide a theoretical basis for appropriate supplementary feeding of cashmere goats. Fifty Inner Mongolian cashmere goats aged 2-4 years old were randomly selected and weighed in May and September 2019, respectively. Based on fasted live-weight gain between the two weights, the experimental ewe goats were divided into two groups: 0-5.0 kg group (n = 30) and 5.0-10.0 kg group (n = 20). Skin samples and cashmere samples were collected. Results of a Pearson correlation analysis showed that fasted live-weight gain during the cashmere non-growing period had a moderate and strong positive correlation with cashmere yield (p = 0.021) and cashmere staple length (p = 0.002), respectively, but did not correlate with cashmere diameter (p = 0.254). Compared with cashmere goats with a fasted live-weight gain of 0-5.0 kg, cashmere goats with a fasted live-weight gain of 5.0-10.0 kg had a 17.10% increase in cashmere yield (p = 0.037) and an 8.09% increase in cashmere staple length (p = 0.045), but had no significant difference in cashmere diameter (p = 0.324). Results of a Pearson correlation analysis showed that there was a strong positive correlation between fasted live-weight gain and the population of active secondary hair follicles in the skin of cashmere goats (p < 0.01). Compared with cashmere goats with a fasted live-weight gain of 0-5.0 kg, cashmere goats with a fasted live-weight gain of 5.0-10.0 kg had an increase in the population of active secondary hair follicles (p < 0.05). In conclusion, the fasted live-weight gain during the cashmere non-growing period had a significant effect on secondary hair follicle activity and cashmere production performance in cashmere goats. Since fasted live-weight gain reflects nutritional level to a certain extent, this study suggests that nutritional manipulations such as supplementary feeding during cashmere non-growing periods can increase cashmere production performance. However, specific nutritional manipulations during the cashmere non-growing period need further research to increase cashmere production performance.

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