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Short cervix is a risk factor for preterm birth. Currently, both international and domestic studies about progesterone's effectiveness are limited to pregnant women at 18-24 weeks gestation. However, multiple studies indicated that cervical length was associated with preterm birth even before 32 weeks of gestation. Therefore, this study expanded the gestational week range to investigate whether progesterone can reduce the rate of preterm birth in singleton pregnant women with a short cervix at 18-32 weeks gestation.Pregnant women who underwent prenatal examination at Peking University First Hospital from January 2016 to August 2020 were prospectively followed. A total of 132 asymptomatic singleton pregnant women at 18-32 weeks gestation with a cervical length <25 mm were ultimately enrolled. According to the method of treatment, the participants were divided into progesterone group (80 patients) and control group (52 patients). The rate of preterm birth (PTB) at different stages was compared between two groups.(1) There was no significant difference in the total preterm birth rate (18.8% vs. 21.2%, RR 0.886[0.442-1.777], p = 0.734). (2) Stratified analysis found that, for pregnant women at <24 weeks gestation, there was a significant difference in the rate of PTB at <32 weeks (2.8% vs. 33.3%, p = 0.021). For women at 24-28weeks gestation, significant difference was not found in the rate of PTB at <37 weeks gestation (25% vs. 42.9%, RR = 0.583[0.186-1.831], p = 0.682), neither for women at after 28 weeks(12.5% vs. 11.1%,1.12[0.27-4.59], p = 1). (3) Vaginal progesterone was not associated with low birth weight (13.8% vs. 19.2%, p = 0.4), or preterm birth-related complications such as respiratory distress syndrome (3.8% vs. 7.7%, p = 0.555), aspiration pneumonia (22.5% vs. 19.2%, p = 0.653) and sepsis (2.5% vs. 7.7%, p = 0.331).For pregnant women with a short cervix at 18-24 weeks gestation, the rate of preterm birth before 32 weeks could be significantly reduced. For women with a short cervix at 24-28 weeks gestation, the rate of preterm birth could be reduced, while there was no significant effect for pregnant women. Further studies with a larger sample size and randomized controlled researches are needed.
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Cuello del Útero , Nacimiento Prematuro , Progesterona , Humanos , Femenino , Embarazo , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/epidemiología , Progesterona/administración & dosificación , Adulto , Administración Intravaginal , Cuello del Útero/efectos de los fármacos , Cuello del Útero/diagnóstico por imagen , Progestinas/administración & dosificación , Estudios Prospectivos , Medición de Longitud Cervical , Edad Gestacional , Estudios de Casos y ControlesRESUMEN
Intermittent hypoxia (IH), a major pathophysiologic alteration in obstructive sleep apnea syndrome (OSAS), is an important contributor to cognitive impairment. Increasing research suggests that melatonin has anti-inflammatory properties and improves functions related to synaptic plasticity. However, it is unclear whether melatonin has a protective effect against OSAS-induced cognitive dysfunction in aged individuals and the involved mechanisms are also unclear. Therefore, in the study, the effects of exposure to IH alone and IH in combination with daily melatonin treatment were investigated in C57BL/6â¯J mice aged 18 months. Assessment of the cognitive ability of mice in a Morris water maze showed that melatonin attenuated IH-induced impairment of learning and memory in aged mice. Enzyme-linked immunosorbent assay, polymerase chain reaction, and western blotting molecular techniques showed that melatonin treatment reduced the levels of the proinflammatory cytokines, interleukin-1ß, interleukin-6, and tumor necrosis factor-α, decreased the levels of NOD-like receptor thermal protein domain associated protein 3 and nuclear factor kappa-B, lowered the levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and increased the levels of the synaptic proteins, activity-regulated cytoskeleton-associated protein, growth-associated protein-43, postsynaptic density protein 95, and synaptophysin in IH-exposed mice. Moreover, electrophysiological results showed that melatonin ameliorated the decline in long-term potentiation induced by IH. The results suggest that melatonin can ameliorate IH-induced cognitive deficits by inhibiting neuroinflammation and improving synaptic plasticity in aged mice.
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Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Enfermedad Injerto contra Huésped/terapia , Investigación Biomédica Traslacional , Esclerosis Amiotrófica Lateral/terapiaRESUMEN
In this study, based on the principle of grating interferometer-based acoustic sensors, design guidelines for the grating interferometric module were obtained and analyzed considering various factors in order to obtain high sensitivity, and a glass-based grating interference component and its acoustic sensor device were developed. The key parameters of the grating interference structure were extracted, and their effects on the acoustic response sensitivity were quantified for multiple mechanisms. For the development of the acoustic sensor, the grating-on-convex-platform structure and the micromachining processes of the glass-based components were designed and developed. The developed acoustic sensor samples achieved high sensitivity. In particular, the sample suitable for low-frequency application obtained a sensitivity of 0.776 V/Pa @ 1 kHz, and the spectrum of its sensitivity was flat from 50 Hz to 8 Hz with a deviation less than 1.5 dB and a sensitivity of 0.408 V/Pa @ 20 Hz.
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Microporous carbon confined nano silicon composites (Si/m-C) are considered to be the best anode materials for high-energy-density lithium-ion batteries compared with the other Si-based materials such as SiO, due to high initial Coulombic efficiency (ICE) and capacity, as well as good cycling stability. However, there is a lack of multilevel comprehensive evaluation of Si/m-C, which poses potential risks to the commercial application. Herein, combined with quantitative titration, mechanical characterization, and bulk/interface evolution analysis, a systematic evolution of commercialized Si/m-C from the particle level to the cylindrical cell level is conducted, revealing the decay mechanism and proposing corresponding solutions. Among them, it is well demonstrated that the Si/m-C still withstands huge volume expansion of over 200% with poor mechanical strength, causing the electrical contact loss of active LixSi and severe interfacial side reactions. Moreover, even blending more than 90% graphite cannot completely suppress its volumetric strain, and the combination of highly flexible single-walled carbon nanotubes (SWCNT) is necessary. In response to this, the 32700-type cylindrical cell with a designed capacity of 9.5 Ah is assembled by mixing Si/m-C with 90% graphite and SWCNT as anode, achieving a long-term cycling stability over 300 cycles at 0.5 C with a capacity retention of 94.8%.
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Anemia is the most common symptom in patients with myelodysplastic syndromes (MDS). Programmed cell death of erythrocytes is one of the contributing factors to anemia. Ferroptosis is a newly identified form of iron-dependent cell death. The aim of this study is to investigate whether anemia in MDS patients is associated with ferroptosis of nucleated erythrocytes(NEs).We detected lipid peroxidation levels, Fe2+ contents, cell death rates, glutathione (GSH) and malondialdehyde (MDA) levels in bone marrow CD235a+ NEs of MDS patients. Expression levels of ferroptosis-related molecules (ACSL4, GPX4, and SLC7A11) were evaluated through qRT-PCR and Western Blotting. Correlation between these markers and clinical parameters were analyzed. To further substantiate that the mode of cell death with CD235a+ NEs of MDS patients was attributed to the ferroptosis pathway, we applied Fer-1 to inhibit ferroptosis. Cell viability was assessed using CCK8, and changes in ferroptosis-related indicators were simultaneously evaluated. We discover that the ferroptosis level of bone marrow NEs in MDS patients was increased, which is related to anemia and iron overload. Ferroptosis might be one of the causes of anemia in MDS patients.
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Ferroptosis , Síndromes Mielodisplásicos , Humanos , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Anciano , Eritrocitos/metabolismo , Eritrocitos/patología , Peroxidación de Lípido , Anemia/patología , Anemia/etiología , Anemia/sangre , Adulto , Anciano de 80 o más Años , Hierro/metabolismo , Hierro/sangreRESUMEN
Spider venom is a natural source of diverse biomolecules, but due to technical limitations, only a small fraction has been studied. With the advancement of omics technologies, research on spider venom has broadened, greatly promoting systematic studies of spider venom. Agelena limbata is a common spider found in vegetation, known for constructing funnel-shaped webs, and feeding on insects such as Diptera and Homoptera. However, due to its small size and the difficulty in obtaining venom, the composition of Agelena limbata venom has never been studied. In this study, a transcriptomics approach was used to analyze the toxin components in the venom of Agelena limbata, resulting in the identification of 28 novel toxin-like sequences and 24 peptidases. Based on sequence similarity and differences in cysteine motifs, the 28-novel toxin-like sequences were classified into 10 superfamilies. According to the results annotated in the database, the 24 peptidases were divided into six distinct families, with the serine protease family being the most common. A phylogenetic tree was constructed using the toxin-like sequences of Agelena limbata along with Psechrus triangulus and Hippasa lycosina. An analysis of the structural domains and motifs of Agelena limbata was also conducted. The results indicated that Agelena limbata is more distantly related to the other two species of funnel-web spiders, and that the toxin superfamily IX has a unique function compared to the other superfamilies. This study reveals the components of the Agelena limbata venom, deepening our understanding of it, and through bioinformatics analysis, has identified unique functions of the toxin superfamilies, providing a scientific basis for the development of bioactive drugs in the future.
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Micro-sensors, such as pressure and flow sensors, are usually adopted to attain actual fluid information around swimming biomimetic robotic fish for hydrodynamic analysis and control. However, most of the reported micro-sensors are mounted discretely on body surfaces of robotic fish and it is impossible to analyzed the hydrodynamics between the caudal fin and the fluid. In this work, a biomimetic caudal fin integrated with a resistive pressure sensor is designed and fabricated by laser machined conductive carbon fibre composites. To analyze the pressure exerted on the caudal fin during underwater oscillation, the pressure on the caudal fin is measured under different oscillating frequencies and angles. Then a model developed from Bernoulli equation indicates that the maximum pressure difference is linear to the quadratic power of the oscillating frequency and the maximum oscillating angle. The fluid disturbance generated by caudal fin oscillating increases with an increase of oscillating frequency, resulting in the decrease of the efficiency of converting the kinetic energy of the caudal fin oscillation into the pressure difference on both sides of the caudal fin. However, perhaps due to the longer stability time of the disturbed fluid, this conversion efficiency increases with the increase of the maximum oscillating angle. Additionally, the pressure variation of the caudal fin oscillating with continuous different oscillating angles is also demonstrated to be detected effectively. It is suggested that the caudal fin integrated with the pressure sensor could be used for sensing thein situflow field in real time and analyzing the hydrodynamics of biomimetic robotic fish.
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Aletas de Animales , Biomimética , Diseño de Equipo , Peces , Robótica , Natación , Animales , Robótica/instrumentación , Aletas de Animales/fisiología , Biomimética/instrumentación , Biomimética/métodos , Peces/fisiología , Natación/fisiología , Hidrodinámica , Análisis de Falla de Equipo , Transductores de Presión , Presión , Materiales Biomiméticos , TransductoresRESUMEN
Methyl farnesoate epoxidase (MFE) is a gene encoding an enzyme related to the last step of juvenile hormone biosynthesis. Mn-MFE cDNA has a total length of 1695 bp and an open reading frame (ORF) length of 1482 bp, encoding 493 amino acids. Sequence analysis showed that its amino acid sequence has a PPGP hinge, an FGCG structural domain, and other structural domains specific to the P450 family of enzymes. Mn-MFE was most highly expressed in the hepatopancreas, followed by the ovary and gill, weakly expressed in heart and muscle tissue, and barely expressed in the eyestalk and cranial ganglion. Mn-MFE expression remained stable during the larval period, during which it mainly played a critical role in gonadal differentiation. Expression in the ovary was positively correlated and expression in the hepatopancreas was negatively correlated with ovarian development. In situ hybridization (ISH) showed that the signal was expressed in the oocyte, nucleus, cell membrane and follicular cells, and the intensity of expression was strongest at stage O-IV. The knockdown of Mn-MFE resulted in a significantly lower gonadosomatic index and percentage of ovaries past stage O-III compared to the control group. However, no differences were found in the cumulative frequency of molting between the experimental and control groups. Moreover, the analysis of ovarian tissue sections at the end of the experiment showed differences between groups in development speed but not in subcellular structure. These results demonstrate that Mn-MFE promotes the ovarian development of Macrobrachium nipponense adults but has no effect on molting.
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Ovario , Palaemonidae , Animales , Ovario/metabolismo , Ovario/crecimiento & desarrollo , Femenino , Palaemonidae/genética , Palaemonidae/crecimiento & desarrollo , Palaemonidae/enzimología , Palaemonidae/metabolismo , Regulación del Desarrollo de la Expresión Génica , Secuencia de Aminoácidos , Filogenia , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Hepatopáncreas/metabolismo , Hepatopáncreas/crecimiento & desarrollo , Ácidos Grasos InsaturadosRESUMEN
The integrated satellite-terrestrial network (ISTN) provides a promising solution to achieve high-data-rate and ubiquitous connectivity in next-generation communication networks. Considering the scarce spectrum resources and unevenly distributed traffic demands, we investigate the resource allocation algorithms for ISTNs, where the beam-hopping (BH)-based satellite system and terrestrial systems share the same frequency band. Taking advantage of the scheduling flexibility of BH technology, the dynamical protection zones are constructed to avoid co-channel interference and improve the spectrum efficiency. Since both spectrum efficiency and user fairness are the key optimization indexes in practical systems, two resource allocation problems are formulated to maximize the weighted sum of capacity (MWSC) and maximize the minimum capacity-to-demand ratio (MMCDR) of ISTNs, respectively. By reformulating the problems as mixed-integer linear programming problems, optimal solutions are obtained. To reduce the computational complexity, two greedy suboptimal algorithms are proposed for the MWSC and MMCDR, respectively. The simulation results show that the proposed algorithms achieve higher spectrum efficiency and guarantee fairness between the satellite and terrestrial systems. It is also shown that both the greedy algorithms perform similarly to the optimal algorithms while having much lower complexity.
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NPC intracellular cholesterol transporter 1 (NPC1) plays an important role in sterol metabolism and transport processes and has been studied in many vertebrates and some insects, but rarely in crustaceans. In this study, we characterized NPC1 from Macrobrachium nipponense (Mn-NPC1) and evaluated its functions. Its total cDNA length was 4283 bp, encoding for 1344 amino acids. It contained three conserved domains typical of the NPC family (NPC1_N, SSD, and PTC). In contrast to its role in insects, Mn-NPC1 was mainly expressed in the adult female hepatopancreas, with moderate expression in the ovary and heart. No expression was found in the embryo (stages CS-ZS) and only weak expression in the larval stages from hatching to the post-larval stage (L1-PL15). Mn-NPC1 expression was positively correlated with ovarian maturation. In situ hybridization showed that it was mainly located in the cytoplasmic membrane and nucleus of oocytes. A 25-day RNA interference experiment was employed to illustrate the Mn-NPC1 function in ovary maturation. Experimental knockdown of Mn-NPC1 using dsRNA resulted in a marked reduction in the gonadosomatic index and ecdysone content of M. nipponense females. The experimental group showed a significant delay in ovarian maturation and a reduction in the frequency of molting. These results expand our understanding of NPC1 in crustaceans and of the regulatory mechanism of ovarian maturation in M. nipponense.
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Proteínas de Artrópodos , Muda , Palaemonidae , Animales , Femenino , Secuencia de Aminoácidos , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Ovario/metabolismo , Ovario/crecimiento & desarrollo , Palaemonidae/genética , Palaemonidae/crecimiento & desarrollo , Palaemonidae/metabolismo , Filogenia , Interferencia de ARNRESUMEN
INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.
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Anestésicos por Inhalación , Disfunción Cognitiva , Hipocampo , Isoflurano , Enfermedades Neuroinflamatorias , Efectos Tardíos de la Exposición Prenatal , Privación de Sueño , Animales , Isoflurano/efectos adversos , Isoflurano/farmacología , Isoflurano/administración & dosificación , Femenino , Disfunción Cognitiva/etiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/fisiopatología , Embarazo , Privación de Sueño/complicaciones , Privación de Sueño/fisiopatología , Ratones , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/farmacología , Anestésicos por Inhalación/administración & dosificación , Sinapsis/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Privación Materna , Factor Neurotrófico Derivado del Encéfalo/metabolismoRESUMEN
Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.
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Resistencia a Antineoplásicos , Ferroptosis , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Transporte de Electrón/efectos de los fármacos , Simulación del Acoplamiento Molecular , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Animales , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , RatonesRESUMEN
Flexible actuation materials play a crucial role in biomimetic robots. Seeking methods to enhance actuation and functionality is one of the directions in which actuators strive to meet the high-performance and diverse requirements of environmental conditions. Herein, by utilizing the method of adsorbing N-doped carbon dots (NCDs) onto SiO2 to form clusters of functional particles, a NCDs@SiO2/PDMS elastomer was prepared and its combined optical and electrical co-stimulation properties were effectively harnessed to develop a biomimetic crawling robot resembling Rhagophthalmus (firefly). The introduction of NCDs@SiO2 cluster particles not only effectively improves the mechanical and dielectric properties of the elastomer but also exhibits fluorescence response and actuation response under the co-stimulation of UV and electricity, respectively. Additionally, a hybrid dielectric elastomer actuator (DEA) with a transparent SWCNT mesh electrode exhibits two notable advancements: an 826% increase in out-of-plane displacement under low electric field stimulation compared to the pure matrix and the ability of NCDs to maintain a stable excited state within the polymer for an extended duration under UV-excitation. Simultaneously, the transparent biomimetic crawling robot can stealthily move in specific environments and fluoresce under UV light.
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BACKGROUND: Vascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported. PURPOSE: We investigated the effects of CDDP on vascular calcification in ApoE-/- mice and in vitro and elucidated its mechanism of action. STUDY DESIGN: Firstly, we found that CDDP has the potential to improve calcification based on network pharmacology analysis. Then, we performed the following experiments: in vivo, ApoE-/- mice were fed a high-fat diet randomly supplemented with CDDP for 16 weeks. Atherosclerosis and vascular calcification were determined. In vitro, human aortic smooth muscle cells (HASMCs), human umbilical vein endothelial cells (HUVECs), and human aortic endothelial cells (HAECs) were used to determine the mechanisms for CDDP-inhibited vascular calcification. RESULTS: In this study, we observed that CDDP reduced intimal calcification in atherosclerotic lesions of ApoE-deficient mice fed a high-fat diet, as well as the calcification in cultured SMCs and ECs. Mechanistically, CDDP inhibited the Wnt/ß-catenin pathway by up-regulating the expression of DKK1 and LRP6, which are upstream inhibitors of Wnt, leading to a reduction in the expression of osteoblastic transition markers (ALP, OPN, BMP2, and RUNX2). Furthermore, CDDP enhanced the secretion of DKK1, which plays a role in mediating EC-SMC crosstalk in calcification. Additionally, VC contributes to vascular aging by inhibiting Sirt1 and increasing senescence parameters (SA-ß-gal, p21, and p16). However, CDDP reversed these changes by activating Sirt1. CDDP also reduced the levels of pro-inflammatory cytokines and the senescence-associated secretory phenotype in vivo and in vitro. CONCLUSIONS: Our study suggests that CDDP reduces vascular calcification by regulating the DKK1/LRP6/ß-catenin signaling pathway in ECs/SMCs and interactions with the crosstalk of ECs and SMCs. It also reduces the senescence of ECs/SMCs, contributing to the Sirt1 activation, indicating CDDP's novel role in ameliorating vascular calcification.
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Aterosclerosis , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Células Endoteliales de la Vena Umbilical Humana , Salvia miltiorrhiza , Calcificación Vascular , Animales , Calcificación Vascular/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/farmacología , Salvia miltiorrhiza/química , Masculino , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/tratamiento farmacológico , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Sirtuina 1/metabolismo , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/efectos de los fármacos , Apolipoproteínas E/genética , Farmacología en Red , Vía de Señalización Wnt/efectos de los fármacos , Aorta/efectos de los fármacos , Canfanos , Péptidos y Proteínas de Señalización Intercelular , Panax notoginsengRESUMEN
Transforming growth factor ß1 (TGFB1) refers to a pleiotropic cytokine exerting contrasting roles in hematopoietic stem cells (HSCs) functions in vitro and in vivo. However, the understanding of hematopoiesis in vivo, when TGFB1 is constantly deactivated, is still unclear, mainly due to significant embryonic lethality and the emergence of a fatal inflammatory condition, which makes doing these investigations challenging. Our study aims to find the specific role of TGFB1 in regulating hematopoiesis in vivo. We engineered mice strains (Vav1 or Mx1 promoter-driven TGFB1 knockout) with conditional knockout of TGFB1 to study its role in hematopoiesis in vivo. In fetal and adult hematopoiesis, TGFB1 KO mice displayed deficiency and decreased self-renewal capacity of HSCs with myeloid-biased differentiation. The results were different from the regulating role of TGFB1 in vitro. Additionally, our results showed that TGFB1 deficiency from fetal hematopoiesis stage caused more severe defect of HSCs than in the adult stage. Mechanistically, our findings identified TGFB1-SOX9-FOS/JUNB/TWIST1 signal axis as an essential regulating pathway in HSCs homeostasis. Our study may provide a scientific basis for clinical HSC transplantation and expansion.
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Hematopoyesis , Células Madre Hematopoyéticas , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Diferenciación Celular , Citocinas/metabolismo , Hematopoyesis/genética , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a highly heterogeneous cancer. This heterogeneity has an impact on the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been found to play regulatory functions in cancer immunity. However, the global landscape of immune-derived lncRNA signatures has not yet been explored in colorectal cancer. METHODS: In this study, we applied DESeq2 to identify differentially expressed lncRNAs in colon cancer. Next, we performed an integrative analysis to globally identify immune-driven lncRNA markers in CRC, including immune-associated pathways, tumor immunogenomic features, tumor-infiltrating immune cells, immune checkpoints, microsatellite instability (MSI) and tumor mutation burden (TMB). RESULTS: We also identified dysregulated lncRNAs, such as LINC01354 and LINC02257, and their clinical relevance in CRC. Our findings revealed that the differentially expressed lncRNAs were closely associated with immune pathways. In addition, we found that RP11-354P11.3 and RP11-545G3.1 had the highest association with the immunogenomic signature. As a result, these signatures could serve as markers to assess immunogenomic activity in CRC. Among the immune cells, resting mast cells and M0 macrophages had the highest association with lncRNAs in CRC. The AC006129.2 gene was significantly associated with several immune checkpoints, for example, programmed cell death protein 1 (PD-1) and B and T lymphocyte attenuator (BTLA). Therefore, the AC006129.2 gene could be targeted to regulate the condition of immune cells or immune checkpoints to enhance the efficacy of immunotherapy in CRC patients. Finally, we identified 15 immune-related lncRNA-generated open reading frames (ORFs) corresponding to 15 cancer immune epitopes. CONCLUSION: In conclusion, we provided a genome-wide immune-driven lncRNA signature for CRC that might provide new insights into clinical applications and immunotherapy.