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1.
Biomaterials ; 313: 122766, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39180916

RESUMEN

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Proteínas de la Membrana , Mitoxantrona , Nucleotidiltransferasas , Factor de Transcripción STAT3 , Mitoxantrona/farmacología , Mitoxantrona/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Animales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Humanos , Nucleotidiltransferasas/metabolismo , Proteínas de la Membrana/metabolismo , Factor de Transcripción STAT3/metabolismo , Ratones , Inmunoterapia/métodos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Benzofuranos , Naftoquinonas
2.
Angew Chem Int Ed Engl ; : e202415940, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39314126

RESUMEN

Single-molecule diode was the first proposed device in molecular electronics. Despite the great efforts and advances over 50 years, the reported rectification ratios, the most critical parameter of a diode, remain moderate for the single-molecule diode. Herein, we report an approach to achieve a larger rectification ratio by adopting the combined strategies of p-type boron doping, the single-layer graphene nodes, and the van der Waals layer-by-layer architecture. Measured current-voltage curves showed one of the as-fabricated single-molecule diodes hit an unprecedented large rectification ratio of 457 at ±1 V. Break junction operations and spectroscopic measurements revealed the three-atom-thick configuration of the single-molecule diodes. With the experimental and theoretical calculation results, we demonstrated the doped boron atoms induced holes to redistribute the electron density, making the asymmetric coupling at positive and negative biases, and the van der Waals interaction promoted asymmetric coupling and significantly boosted diode performance.

3.
Front Nutr ; 11: 1378853, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39279900

RESUMEN

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength. Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively. Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (ß = 0.05747, p = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 µg/d (P nonlinear = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements. Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range.

4.
Toxins (Basel) ; 16(9)2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39330849

RESUMEN

(1) Background: With the increasing aesthetic pursuit of facial features, the clinical use of Botulinum Toxin Type A (BoNT-A) injections for masseter hypertrophy has been on the rise. However, due to variations in masseter muscle structure and differences in clinicians' injection techniques, blind injections may lack precision, potentially compromising treatment accuracy and increasing the risk of complications. (2) Objectives: The study aims to use ultrasonography to detail the deep inferior tendon (DIT) within the masseter muscle in a young Chinese cohort, refine its classification, analyze muscle belly thickness and variations across groups, and propose a customized ultrasound-guided BoNT-A injection protocol. (3) Methods: Ultrasound imaging was used to observe the bilateral masseter muscles at rest and during clenching. The features of the DIT were classified from these images, and the thickness of the masseter's distinct bellies associated with the DIT types was measured in both states. (4) Results: The study cohort included 103 participants (27 male, 76 female), with 30 muscles in the normal masseter group and 176 muscles in the hypertrophy group. The DIT was categorized as Type A, B (subtypes B1, B2), and C. The distribution of these types was consistent across normal, hypertrophic, and gender groups, all following the same trend (B > A > C). In hypertrophy, Type B1 showed uniform thickness across masseter bellies, B2 presented with a thinner intermediate belly, and Type C had mainly superficial muscle enlargement. Changes in muscle thickness during clenching were noted but not statistically significant among different bellies. (5) Conclusions: The study evidences individual variation in the DIT, highlighting the importance of precise DIT classification for effective BoNT-A injections. A tailored ultrasound-guided BoNT-A injection strategy based on this classification may enhance safety and efficacy of the therapy.


Asunto(s)
Toxinas Botulínicas Tipo A , Hipertrofia , Músculo Masetero , Tendones , Ultrasonografía , Músculo Masetero/diagnóstico por imagen , Músculo Masetero/efectos de los fármacos , Músculo Masetero/anomalías , Humanos , Masculino , Femenino , Toxinas Botulínicas Tipo A/administración & dosificación , Hipertrofia/diagnóstico por imagen , Adulto Joven , Tendones/diagnóstico por imagen , Tendones/efectos de los fármacos , Inyecciones Intramusculares , Fármacos Neuromusculares/administración & dosificación , Adulto , Adolescente
5.
ACS Sens ; 9(9): 4578-4590, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39223701

RESUMEN

The real-time and room-temperature detection of nitrogen dioxide (NO2) holds significant importance for environmental monitoring. However, the performance of NO2 sensors has been hampered by the trade-off between the high sensitivity and stability of conventional sensitive materials. Here, we present a novel fully flexible paper-based gas sensing structure by combining a homogeneous screen-printed titanium carbide (Ti3C2Tx) MXene-based nonmetallic electrode with a MoS2 quantum dots/Ti3C2Tx (MoS2 QDs/Ti3C2Tx) gas-sensing film. These precisely designed gas sensors demonstrate an improved response value (16.3% at 5 ppm) and a low theoretical detection limit of 12.1 ppb toward NO2, which exhibit a remarkable 3.5-fold increase in sensitivity compared to conventional Au interdigital electrodes. The outstanding performance can be attributed to the integration of the quantum confinement effect of MoS2 QDs and the conductivity of Ti3C2Tx, establishing the main active adsorption sites and enhanced charge transport pathways. Furthermore, an end-sealing effect strategy was applied to decorate the defect sites with naturally oxygen-rich tannic acid and conductive polymer, and the formed hydrogen bonding network at the interface effectively mitigated the oxidative degradation of the Ti3C2Tx-based gas sensors. The exceptional stability has been achieved with only a 1.8% decrease in response over 4 weeks. This work highlights the innovative design of high-performance gas sensing materials and homogeneous gas sensor techniques.


Asunto(s)
Electrodos , Dióxido de Nitrógeno , Puntos Cuánticos , Titanio , Dióxido de Nitrógeno/análisis , Titanio/química , Puntos Cuánticos/química , Molibdeno/química , Límite de Detección , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Gases/química , Gases/análisis , Disulfuros
6.
Nitric Oxide ; 152: 58-68, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39313019

RESUMEN

Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1-4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l-valine) and characterized by 1H NMR, 13C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1-4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.

8.
BMJ Open ; 14(9): e088079, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39231550

RESUMEN

OBJECTIVES: We aimed to explore the lived experiences and needs of women after a recent stillbirth event. DESIGN: Qualitative phenomenological study. SETTING: The current study was conducted in a tertiary obstetric hospital in East China between 25 January 2024 and 29 March 2024. PARTICIPANTS: 14 women having experienced a stillbirth within the last 6 months. RESULTS: Researchers agreed on four key themes including individual variations in emotional reaction and recovery, physical recovery and concerns about future pregnancies, the critical role of social support systems and variations in perceptions of stillbirth as the death of a fetus versus a human being, along with related mourning rituals. These themes collectively highlight the multifaceted nature of the stillbirth experience, underscoring the complex interplay between personal, cultural and medical factors that shape women's emotional and physical responses. CONCLUSIONS: Post-stillbirth experiences among Chinese women are deeply individualised and influenced by a complex interplay of personal emotions, cultural contexts and medical interactions. It is imperative for healthcare systems to implement tailored care strategies beyond standard protocols to proactively address their varied emotional landscapes and physical concerns with an enhanced awareness of cultural sensitivities. Specialised training for healthcare providers should be devised to recognise and respond to the unique grief processes. Comprehensive support systems should be established to significantly enhance the recovery journey by providing essential resources and community connections.


Asunto(s)
Pesar , Investigación Cualitativa , Apoyo Social , Mortinato , Humanos , Femenino , Mortinato/psicología , Adulto , China , Embarazo , Emociones , Adulto Joven , Pueblos del Este de Asia
9.
EMBO J ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261664

RESUMEN

In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural killer (dNK) cells were found to inhibit DSC senescence by interacting with its ligand TNFRSF14. As in mice fed high-leucine diets, both mice with NK cell depletion and Tnfrsf14-deficient mice with excessive uterine senescence experienced adverse pregnancy outcomes. Further, we found excessive uterine senescence, SLC3A2-mediated BCAA intake, and insufficient TNFRSF14 expression in the decidua of patients with recurrent spontaneous abortion. In summary, this study suggests that dNK cells maintain senescence homeostasis of DSCs via TNFSF14/TNFRSF14, providing a potential therapeutic strategy to prevent DSC senescence-associated spontaneous abortion.

10.
J Inflamm Res ; 17: 5711-5721, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219814

RESUMEN

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

11.
Br J Pharmacol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39228119

RESUMEN

BACKGROUND AND PURPOSE: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). EXPERIMENTAL APPROACH: The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE-/- mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2-/- macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2-/- mice treated with high-fat diet (HFD) and AAV-PCSK9. KEY RESULTS: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. CONCLUSION AND IMPLICATIONS: PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS.

12.
Cardiology ; : 1-16, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284297

RESUMEN

INTRODUCTION: We sought to comprehensively explore the potential linear and nonlinear relationship between preoperative iron metabolism and perioperative myocardial injury (PMI) following cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected. The measurements of iron metabolism included serum iron (SI), serum ferritin (SF), transferrin (TRF), transferrin saturation (TS), and total iron binding capacity (TIBC). Logistic regression and restricted cubic spline (RCS) models were used for linear and nonlinear analysis. The primary outcome was PMI with a 100x upper reference limit (URL). RESULTS: Of 2420 patients screened,744 eligible patients were enrolled for the final analysis. The incidence of PMI was 25.7%. No significant linear relationship was observed. In the RCS models adjusted with age (median:56), female, and history of diabetes, a statistically significant difference was detected between TRF (p for nonlinear 0.0152) or TIBC (p for nonlinear 0.0477) and PMI. The gentle U-shaped relationship observed between TRF, TIBC, and PMI suggests that when TRF and TIBC increase, the risk decreases, reaching its lowest point when TRF=2.4 and TIBC=54. Nevertheless, as TRF and TIBC continue to increase, the risk starts to rise again. Subgroup analyses yielded consistent findings, with a notable emphasis on older patients who were more susceptible to variations in iron metabolism. CONCLUSION: Iron metabolism, including TRF, and TIBC, exhibited a nonlinear relationship with PMI by the RCS model adjusted by age, gender, and history of diabetes.

13.
Neuroscience ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293730

RESUMEN

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

14.
Mol Biol Rep ; 51(1): 976, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259343

RESUMEN

OBJECTIVE: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). DESIGN: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related ß-galactosidase (SA-ß-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. RESULTS: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-ß-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). CONCLUSIONS: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.


Asunto(s)
Senescencia Celular , Fibroblastos , Encía , Factor 2 Relacionado con NF-E2 , Porphyromonas gingivalis , Especies Reactivas de Oxígeno , Sirtuinas , Humanos , Porphyromonas gingivalis/patogenicidad , Encía/microbiología , Encía/metabolismo , Fibroblastos/metabolismo , Sirtuinas/metabolismo , Sirtuinas/genética , Masculino , Femenino , Adulto , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos/farmacología , Periodontitis/microbiología , Periodontitis/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Persona de Mediana Edad , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética
15.
Int J Mol Sci ; 25(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39273657

RESUMEN

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.


Asunto(s)
Aborto Espontáneo , Decidua , Hipoxia , Macrófagos , Femenino , Humanos , Embarazo , Macrófagos/metabolismo , Macrófagos/inmunología , Aborto Espontáneo/metabolismo , Decidua/metabolismo , Hipoxia/metabolismo , Animales
16.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167469, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39153664

RESUMEN

Premature ovarian insufficiency (POI) critically affects female reproductive health, with obesity being a significant and recognized risk factor. Interleukin-27 (IL-27), known for its role in immune modulation and inflammation, has garnered attention in metabolic syndrome research. Nonetheless, the role of these immunometabolic factors on the initiation of POI remains to be unraveled. Our investigation delves into the influence of impaired IL-27 signaling on POI induction, particularly under the challenge of a high-fat diet (HFD). We analyzed patients' serum profiles and established a correlation of increased serum triglycerides with decreased IL-27 levels in POI cases. Experiments on C57BL/6 mice lacking the IL-27 receptor alpha (Il27ra-/-) revealed that when subjected to HFD, these mice developed hallmark POI symptoms. This includes escalated lipid deposition in both liver and ovarian tissues, increased ovarian macrophages cellular aging, and diminished follicle count, all pointing to compromised ovarian function. These findings unveil a novel pathway wherein impaired IL-27 signaling potentiates the onset of POI in the presence of HFD. Understanding the intricate interplay between IL-27, metabolic alterations, and immune dysregulation sheds light on potential therapeutic avenues for managing POI, offering hope for improved reproductive health outcomes.


Asunto(s)
Dieta Alta en Grasa , Macrófagos , Insuficiencia Ovárica Primaria , Receptores de Interleucina , Transducción de Señal , Adulto , Animales , Femenino , Humanos , Ratones , Senescencia Celular , Dieta Alta en Grasa/efectos adversos , Interleucinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Ovario/metabolismo , Ovario/patología , Insuficiencia Ovárica Primaria/patología , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/inmunología , Receptores de Interleucina/metabolismo , Receptores de Interleucina/genética
17.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167480, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39209235

RESUMEN

Electroacupuncture has been demonstrated to mitigate endotoxin-induced acute lung injury by enhancing mitochondrial function. This study investigates whether electroacupuncture confers lung protection through the regulation of mitochondrial quality control mediated by heme oxygenase-1 (HO-1) and the mitochondrial inner membrane protein MIC60. HO-1, an inducible stress protein, is crucial for maintaining mitochondrial homeostasis and protecting against lung injury. MIC60, a key component of the mitochondrial contact site and cristae organizing system, supports mitochondrial integrity. We employed genetic knockout/silencing and cell transfection techniques to model lipopolysaccharide (LPS)-induced lung injury, assessing changes in mitochondrial structure, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and the expression of proteins essential for mitochondrial quality control. Our findings reveal that electroacupuncture alleviates endotoxin-induced acute lung injury and associated mitochondrial dysfunction, as evidenced by reductions in lung injury scores, decreased ROS production, and suppressed expression of proteins involved in mitochondrial fission and mitophagy. Additionally, electroacupuncture enhanced MMP and upregulated proteins that facilitate mitochondrial fusion and biogenesis. Importantly, the protective effects of electroacupuncture were reduced in models with Hmox1 knockout or Mic60 silencing, and in macrophages transfected with Hmox1-siRNA or Mic60-siRNA. Moreover, HO-1 was found to influence MIC60 expression during electroacupuncture preconditioning and LPS challenge, demonstrating that these proteins not only co-localize but also interact directly. In conclusion, electroacupuncture effectively modulates mitochondrial quality control through the HO-1/MIC60 signaling pathway, offering an adjunctive therapeutic strategy to ameliorate endotoxin-induced acute lung injury in both in vivo and in vitro settings.


Asunto(s)
Lesión Pulmonar Aguda , Electroacupuntura , Hemo-Oxigenasa 1 , Mitocondrias , Transducción de Señal , Electroacupuntura/métodos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/prevención & control , Lesión Pulmonar Aguda/terapia , Animales , Mitocondrias/metabolismo , Ratones , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Masculino , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Lipopolisacáridos/toxicidad , Potencial de la Membrana Mitocondrial , Endotoxinas , Humanos , Dinámicas Mitocondriales , Proteínas de la Membrana
18.
Naturwissenschaften ; 111(5): 45, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141101

RESUMEN

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.


Asunto(s)
Reproducción , Animales , Reproducción/efectos de los fármacos , Reproducción/fisiología , Humanos , Benzoxazoles
19.
Medicine (Baltimore) ; 103(32): e39277, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121268

RESUMEN

RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.


Asunto(s)
Coma , Medicamentos Herbarios Chinos , Humanos , Masculino , Coma/etiología , Coma/tratamiento farmacológico , Coma/terapia , Medicamentos Herbarios Chinos/uso terapéutico , Adolescente , Electroencefalografía , Terapias Complementarias/métodos , Lesiones Traumáticas del Encéfalo/complicaciones , Medicina Tradicional China/métodos
20.
Nat Commun ; 15(1): 6741, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39112466

RESUMEN

The development of highly efficient and durable alkaline hydrogen evolution reaction (HER) catalysts is crucial for achieving high-performance practical anion exchange membrane water electrolyzer (AEMWE) at ampere-level current density. Herein, we report a design concept by employing Ga single atoms as an electronic bridge to stabilize the Ru clusters for boosting alkaline HER performance in practical AEMWE. Experimental and theoretical results collectively reveal that the bridged Ga sites trigger strong metal-support interaction for the homogeneous distribution of Ru clusters with high density, as well as optimize the Ru-H bond strength due to the electron transfer between Ru and Ga for enhanced intrinsic HER activity. Moreover, the oxophilic Ga sites near the Ru clusters tend to adsorb the hydroxyl species and accelerate the water dissociation for sufficient proton supplement in an alkaline medium. The Ru-GaSA/N-C catalyst exhibits a low overpotential of 4 ± 1 mV (10 mA cm-2) and high mass activity of 9.3 ± 0.5 A mg-1Ru at -0.05 V vs RHE. In particular, the Ru-GaSA/N-C-based AEMWE in 1 M KOH delivers a voltage of only 1.74 V to reach an industrial current density of 1 A cm-2, and can steadily operate at 1 A cm-2 for more than 170 h.

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