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1.
Int J Womens Health ; 16: 1517-1531, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309199

RESUMEN

Background: Although there are many benign tumors in the ovarian adnexal area, the four most common types are still luteal cyst, ovarian mature cystic teratoma (OMCT), ovarian endometriosis, and benign epithelial tumors of the ovary. Purpose: This study aimed to examine the correlation between six tumor markers (CEA, AFP, CA125, CA19-9, SCC, HE4) in the differential diagnosis of female adnexal benign masses and assess their diagnostic value. Patients and Methods: In this study, 135 patients with adnexal benign masses were treated in Zhengzhou first people's Hospital from January 2018 to January 2023. 135 patients were divided into four groups: luteal cyst (13.3%), OMCT (42.2%), ovarian endometriosis (23.7%) and benign epithelial tumors of the ovary (including mucinous cystadenoma and serous cystadenoma) in group D. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection. Results: The diameter of luteal cysts was significantly smaller than that of benign ovarian tumors (p < 0.001). ROC analysis showed that the combination of AFP, CA125, CA19-9, and SCC had a higher diagnostic rate for luteal cysts (AUC=0.871; sensitivity: 71.8%; specificity: 88.9). The SCC level in OMCT was significantly higher than in other benign ovarian tumors (p=0.007). ROC analysis indicated that the combination of AFP, HE4, and SCC had a higher diagnostic rate for OMCT (AUC=0.753; sensitivity: 65.4%; specificity: 75.4%). The CA125 level in ovarian endometriosis was significantly higher than in other accessory benign tumors (p < 0.001). ROC analysis demonstrated that the combination of AFP, CA125, and CA19-9 had a higher diagnostic rate for ovarian endometriosis (AUC=0.935; sensitivity: 76.7%; specificity: 96.9%). The tumor diameter of benign epithelial tumors of the ovary was significantly larger than that of other benign ovarian tumors (p < 0.001). ROC analysis revealed that the combination of CA125 and CA19-9 had a higher diagnostic rate for benign epithelial tumors of the ovary (AUC=0.792; sensitivity: 64.5%; specificity: 85.7%). Conclusion: The findings of this study demonstrate that the combined use of tumor markers (CEA, AFP, CA125, CA19-9, SCC, and HE4) has value in diagnosing benign ovarian tumors, including luteal cysts, OMCT, ovarian endometriosis, and benign epithelial tumors of the ovary. However, it is important to acknowledge the limitations of this study, which include its single-center nature and the small sample size. Despite these limitations, the results highlight the potential utility of these markers in clinical practice.

2.
Sci Rep ; 14(1): 18956, 2024 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147837

RESUMEN

This study aims to assess the global prevalence of kinesiophobia and the potential influencing factors among patients with heart disease. A comprehensive search was conducted in PubMed, Embase, Web of Science, PsycINFO, and Scopus databases to identify studies reporting on the prevalence of kinesiophobia and its influencing factors in heart disease patients up to January 2024. A random-effects model was employed to aggregate prevalence rates. Heterogeneity sources were investigated through subgroup analysis, while differences in the prevalence of kinesiophobia across regions, types of heart disease, and gender were evaluated. Additionally, a qualitative analysis of the factors influencing kinesiophobia was performed. This research incorporated 15 studies from six countries, with 14 providing data on the prevalence of kinesiophobia and nine exploring its potential influencing factors. The findings indicated that the overall prevalence of kinesiophobia among heart disease patients was 61.0% (95% CI 49.4-72.6%). Subgroup analysis revealed that the prevalence in upper-middle-income countries was 71.8% (95% CI 66.2-77.4%), while it stands at 49.9% (95% CI 30.2-69.5%) in high-income countries. The prevalence rates among patients with coronary artery disease, heart failure, and atrial fibrillation were 63.2% (95% CI 45.2-81.3%), 69.2% (95% CI 57.6-80.8%), and 71.6% (95% CI 67.1-76.1%), respectively. Gender-wise, no significant difference was observed in the prevalence of kinesiophobia between men and women (52.2% vs. 51.8%). A total of 24 potential influencing factors of kinesiophobia were identified, with education level, monthly income, anxiety, and exercise self-efficacy being the most recognized. The prevalence of kinesiophobia in patients with heart disease is notably high and is influenced by a multitude of factors. Early implementation of targeted preventive measures is imperative to mitigate the incidence of kinesiophobia in this population.


Asunto(s)
Cardiopatías , Kinesiofobia , Femenino , Humanos , Masculino , Ejercicio Físico , Cardiopatías/psicología , Kinesiofobia/epidemiología , Kinesiofobia/psicología , Prevalencia
3.
Proc Natl Acad Sci U S A ; 121(35): e2408843121, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39163329

RESUMEN

The topological physics has sparked intensive investigations into topological lattices in photonic, acoustic, and mechanical systems, powering counterintuitive effects otherwise inaccessible with usual settings. Following the success of these endeavors in classical wave dynamics, there has been a growing interest in establishing their topological counterparts in diffusion. Here, we propose an additional real-space dimension in diffusion, and the system eigenvalues are transformed from "imaginary" to "real." By judiciously tailoring the effective Hamiltonian with coupling networks, localized and delocalized topological modes are realized in heat transfer. Simulations and experiments in active thermal lattices validate the effectiveness of the proposed theoretical strategy. This approach can be applied to establish various topological lattices in diffusion systems, offering insights into engineering topologically protected edge states in dynamic diffusive scenarios.

4.
Cell Death Dis ; 15(7): 473, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956064

RESUMEN

Damage to renal tubular epithelial cells (RTECs) signaled the onset and progression of sepsis-associated acute kidney injury (SA-AKI). Recent research on mitochondria has revealed that mitophagy plays a crucial physiological role in alleviating injury to RTECs and it is suppressed progressively by the inflammation response in SA-AKI. However, the mechanism by which inflammation influences mitophagy remains poorly understood. We examined how macrophage migration inhibitory factor (MIF), a pro-inflammatory protein, influences the PINK1-Parkin pathway of mitophagy by studying protein-protein interactions when MIF was inhibited or overexpressed. Surprisingly, elevated levels of MIF were found to directly bind to PINK1, disrupting its interaction with Parkin. This interference hindered the recruitment of Parkin to mitochondria and impeded the initiation of mitophagy. Furthermore, this outcome led to significant apoptosis of RTECs, which could, however, be reversed by an MIF inhibitor ISO-1 and/or a new mitophagy activator T0467. These findings highlight the detrimental impact of MIF on renal damage through its disruption of the interaction between PINK1 and Parkin, and the therapeutic potential of ISO-1 and T0467 in mitigating SA-AKI. This study offers a fresh perspective on treating SA-AKI by targeting MIF and mitophagy.


Asunto(s)
Lesión Renal Aguda , Factores Inhibidores de la Migración de Macrófagos , Mitofagia , Proteínas Quinasas , Sepsis , Ubiquitina-Proteína Ligasas , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas Quinasas/metabolismo , Sepsis/complicaciones , Sepsis/metabolismo , Animales , Humanos , Mitocondrias/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Apoptosis , Unión Proteica , Masculino , Oxidorreductasas Intramoleculares/metabolismo
6.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39000589

RESUMEN

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.


Asunto(s)
Alanina , MAP Quinasa Quinasa 1 , Simulación de Dinámica Molecular , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 1/química , Alanina/análogos & derivados , Alanina/química , Alanina/farmacología , Alanina/metabolismo , Humanos , Dominio Catalítico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Activación Enzimática/efectos de los fármacos , Bencimidazoles/farmacología , Bencimidazoles/química
7.
MedComm (2020) ; 5(5): e546, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38706740

RESUMEN

Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, pulmonary fibrosis, asthma, pulmonary infections due to pathogen invasion, and fatal lung cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These modifications not only shape cell fates but also finely modulate the expression of genes linked to disease progression, suggesting their utility as biomarkers and targets for therapeutic strategies. The critical RNA modifications implicated in PDs are summarized in this review, including N6-methylation of adenosine, N1-methylation of adenosine, 5-methylcytosine, pseudouridine (5-ribosyl uracil), 7-methylguanosine, and adenosine to inosine editing, along with relevant regulatory mechanisms. By shedding light on the pathology of PDs, these summaries could spur the identification of new biomarkers and therapeutic strategies, ultimately paving the way for early PD diagnosis and treatment innovation.

8.
Nano Lett ; 24(20): 5958-5967, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38738749

RESUMEN

Micro/nanorobots hold the potential to revolutionize biomedicine by executing diverse tasks in hard-to-reach biological environments. Nevertheless, achieving precise drug delivery to unknown disease sites using swarming micro/nanorobots remains a significant challenge. Here we develop a heterogeneous swarm comprising sensing microrobots (sensor-bots) and drug-carrying microrobots (carrier-bots) with collaborative tasking capabilities for precise drug delivery toward unknown sites. Leveraging robust interspecific hydrodynamic interactions, the sensor-bots and carrier-bots spontaneously synchronize and self-organize into stable heterogeneous microswarms. Given that the sensor-bots can create real-time pH maps employing pH-responsive structural-color changes and the doxorubicin-loaded carrier-bots exhibit selective adhesion to acidic targets via pH-responsive charge reversal, the sensor-carrier microswarm, when exploring unknown environments, can detect and localize uncharted acidic targets, guide itself to cover the area, and finally deploy therapeutic carrier-bots precisely there. This versatile platform holds promise for treating diseases with localized acidosis and inspires future theranostic microsystems with expandability, task flexibility, and high efficiency.


Asunto(s)
Doxorrubicina , Sistemas de Liberación de Medicamentos , Doxorrubicina/química , Doxorrubicina/farmacología , Concentración de Iones de Hidrógeno , Acidosis , Humanos , Portadores de Fármacos/química , Robótica
9.
Front Cardiovasc Med ; 11: 1334457, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606383

RESUMEN

Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.

10.
Mol Nutr Food Res ; 68(5): e2300784, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38314939

RESUMEN

SCOPE: Premature ovarian insufficiency (POI) is a common female infertility problem, with its pathogenesis remains unknown. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of α-ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms. METHODS AND RESULTS: POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate-limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, Interleukin-18 (IL-18), and Interleukin-1 beta (IL-1ß). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect. CONCLUSION: AKG ameliorates CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.


Asunto(s)
Reserva Ovárica , Insuficiencia Ovárica Primaria , Humanos , Ratas , Femenino , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácidos Cetoglutáricos/farmacología , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Piroptosis , Células de la Granulosa/metabolismo , Inflamasomas/metabolismo
11.
Postgrad Med J ; 100(1182): 219-227, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38244550

RESUMEN

BACKGROUND: The lack of transparency is a prevalent issue among the current machine-learning (ML) algorithms utilized for predicting mortality risk. Herein, we aimed to improve transparency by utilizing the latest ML explicable technology, SHapley Additive exPlanation (SHAP), to develop a predictive model for critically ill patients. METHODS: We extracted data from the Medical Information Mart for Intensive Care IV database, encompassing all intensive care unit admissions. We employed nine different methods to develop the models. The most accurate model, with the highest area under the receiver operating characteristic curve, was selected as the optimal model. Additionally, we used SHAP to explain the workings of the ML model. RESULTS: The study included 21 395 critically ill patients, with a median age of 68 years (interquartile range, 56-79 years), and most patients were male (56.9%). The cohort was randomly split into a training set (N = 16 046) and a validation set (N = 5349). Among the nine models developed, the Random Forest model had the highest accuracy (87.62%) and the best area under the receiver operating characteristic curve value (0.89). The SHAP summary analysis showed that Glasgow Coma Scale, urine output, and blood urea nitrogen were the top three risk factors for outcome prediction. Furthermore, SHAP dependency analysis and SHAP force analysis were used to interpret the Random Forest model at the factor level and individual level, respectively. CONCLUSION: A transparent ML model for predicting outcomes in critically ill patients using SHAP methodology is feasible and effective. SHAP values significantly improve the explainability of ML models.


Asunto(s)
Inteligencia Artificial , Enfermedad Crítica , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos , Algoritmos , Cuidados Críticos
12.
Ultrason Sonochem ; 102: 106714, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113586

RESUMEN

A growing interest in the development of efficient strategies for the removal of organic pollutants from polluted water is emerging. As such, artificial micro/nano machines performing excellent water purification tasks have recently attracted more research attention of scientists. Hereby a spinous Fe3O4@PPy microrobot is presented that towards an efficient organic pollutant removal by enhancing Fenton-like reaction. The microrobot is fabricated by wrapping polypyrrole (PPy) on a spiny magnetic template prepared from sunflowers pollen. Modulating the sound pressure and frequency of the ultrasonic field enables the Fe3O4@PPy microrobot to present multimode motion, such as violent eruption-like motion caused by local cavitation (ELM), march-like unific motion (MLM), and typhoon-like rotation toward the center gathered motion (TLM). This multimode motion achieves the sufficient locomotion of microrobots in three-dimensional space and effective contact with organic pollutants in polluted water. Furthermore, a 5.2-fold increase in the degradation rate of methylene blue has been realized using Fe3O4@PPy microrobots under low-concentration hydrogen peroxide conditions. Also, the magnetically controlled recovery of microrobots from water after the completion of the degradation task has been demonstrated. The magnetic-acoustic actuated spinous microrobot can be extrapolated to other catalytic microrobot, developing a new strategy for an easier implementation and recovery of microrobot in real applications of water purification.

13.
Cell Death Dis ; 14(11): 723, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37935689

RESUMEN

Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs' pyroptosis in obese men.


Asunto(s)
Proteína con Dominio Pirina 3 de la Familia NLR , Proproteína Convertasa 9 , Humanos , Ratones , Animales , Masculino , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Cofactor PQQ/farmacología , Ratones Obesos , Células Intersticiales del Testículo/metabolismo , Piroptosis , Obesidad/metabolismo , Inflamación
14.
iScience ; 26(11): 108320, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38026188

RESUMEN

Swimming microrobot energized by magnetic fields exhibits remotely propulsion and modulation in complex biological experiment with high precision. However, achieving high environment adaptability and multiple tasking capability in one configuration is still challenging. Here, we present a strategy that use oriented magnetized Janus spheres to assemble the microdimer robots with two magnetic distribution configurations of head-to-side configuration (HTS-config) and head-to-head configuration (HTH-config), achieving performance of multiple tasks through multimode transformation and locomotion. Modulating the magnetic frequency enables multimode motion transformation between tumbling, rolling, and swing motion with different velocities. The dual-asynchronization mechanisms of HTS-config and HTH-config robot dependent on magnetic dipole-dipole angle are investigated by molecular dynamic simulation. In addition, the microdimer robot can transport cell crossing morphological rugae or complete drug delivery on tissues by switching motion modes. This microdimer robot can provide versatile motion modes to address environmental variations or multitasking requirements.

15.
Front Immunol ; 14: 1271919, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37809079

RESUMEN

Background: Post-operative etiological studies are critical for infection prevention in lung transplant recipients within the first year. In this study, mNGS combined with microbial culture was applied to reveal the etiological characteristics within one week (ultra-early) and one month (early) in lung transplant recipients, and the epidemiology of infection occurred within one month. Methods: In 38 lung transplant recipients, deep airway secretions were collected through bronchofiberscope within two hours after the operation and were subjected to microbial identification by mNGS and microbial culture. The etiologic characteristics of lung transplant recipients were explored. Within one month, the infection status of recipients was monitored. The microbial species detected by mNGS were compared with the etiological agents causing infection within one month. Results: The detection rate of mNGS in the 38 airway secretions specimens was significantly higher than that of the microbial culture (P<0.0001). MNGS identified 143 kinds of pathogenic microorganisms; bacterial pathogens account for more than half (72.73%), with gram-positive and -negative bacteria occupying large proportions. Fungi such as Candida are also frequently detected. 5 (50%) microbial species identified by microbial culture had multiple drug resistance (MDR). Within one month, 26 (68.42%) recipients got infected (with a median time of 9 days), among which 10 (38.46%) cases were infected within one week. In the infected recipients, causative agents were detected in advance by mNGS in 9 (34.62%) cases, and most of them (6, 66.67%) were infected within one week (ultra-early). In the infection that occurred after one week, the consistency between mNGS results and the etiological agents was decreased. Conclusion: Based on the mNGS-reported pathogens in airway secretions samples collected within two hours, the initial empirical anti-infection regimes covering the bacteria and fungi are reasonable. The existence of bacteria with MDR forecasts the high risk of infection within 48 hours after transplant, reminding us of the necessity to adjust the antimicrobial strategy. The predictive role of mNGS performed within two hours in etiological agents is time-limited, suggesting continuous pathogenic identification is needed after lung transplant.


Asunto(s)
Trasplante de Pulmón , Receptores de Trasplantes , Humanos , Causalidad , Trasplante de Pulmón/efectos adversos , Tórax , Pulmón
16.
J Am Chem Soc ; 145(38): 20761-20766, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37699413

RESUMEN

Signal transduction processes in living organisms are mainly transmitted through conformational changes in transmembrane protein receptors. So far, the development of signal transduction models induced by artificial simulation of conformational changes remains limited. We herein report a new artificial receptor that achieves controllable "ON/OFF" signal transduction through conformational changes between the folding and unfolding of a transmembrane foldamer moiety. The receptor contains three functional modules: a lipid-anchored cholic acid headgroup, a foldamer transmembrane moiety, and a precatalyst tailgroup. After inserting in the lipid membrane, the addition of Zn2+ induces unfolding of the foldamer, which changes the molecular conformation and activates the tailgroup to enter the cavity to perform its catalytic task, resulting in signal transduction in an "ON" state. By further adding a competitive ligand to bind Zn2+, the transduction can be turned "OFF". External signals can be used to reversibly switch intravesicular catalysis on and off, which provides a new model for constructing artificial signal transduction systems.


Asunto(s)
Receptores Artificiales , Transducción de Señal , Conformación Molecular , Proteínas de la Membrana , Lípidos , Conformación Proteica
17.
Biomed Pharmacother ; 163: 114401, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37167721

RESUMEN

PF-543 is a sphingosine kinase 1(SPHK1)inhibitor developed by Pfizer and is currently considered the most potent selective SPHK1 inhibitor. SPHK1 catalyses the production of sphingosine 1-phosphate (S1P) from sphingosine. It is the rate-limiting enzyme of S1P production, and there is substantial evidence to support a very important role for sphingosine kinase in health and disease. This review is the first to summarize the role and mechanisms of PF-543 as an SPHK1 inhibitor in anticancer, antifibrotic, and anti-inflammatory processes, providing new therapeutic leads and ideas for future research and clinical trials.


Asunto(s)
Fosfotransferasas (Aceptor de Grupo Alcohol) , Esfingosina
18.
Sci Adv ; 9(18): eadg4501, 2023 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-37146139

RESUMEN

Swimming microrobots guided in the circulation system offer considerable promise in precision medicine but currently suffer from problems such as limited adhesion to blood vessels, intensive blood flow, and immune system clearance-all reducing the targeted interaction. A swimming microrobot design with clawed geometry, a red blood cell (RBC) membrane-camouflaged surface, and magnetically actuated retention is discussed, allowing better navigation and inspired by the tardigrade's mechanical claw engagement, coupled to an RBC membrane coating, to minimize blood flow impact. Using clinical intravascular optical coherence tomography in vivo, the microrobots' activity and dynamics in a rabbit jugular vein was monitored, illustrating very effective magnetic propulsion, even against a flow of ~2.1 cm/s, comparable with rabbit blood flow characteristics. The equivalent friction coefficient with magnetically actuated retention is elevated ~24-fold, compared to magnetic microspheres, achieving active retention at 3.2 cm/s, for >36 hours, showing considerable promise across biomedical applications.


Asunto(s)
Sistema Cardiovascular , Natación , Animales , Conejos , Natación/fisiología , Magnetismo
19.
Front Cell Infect Microbiol ; 13: 1064760, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37091672

RESUMEN

Background: Human Parvovirus B19 (PB19) is a single-stranded DNA virus. Septic shock from viremia is rare with PB19; however, this infection can progress to life-threatening conditions. We report the first case of severe septic shock associated with a PB19 infection after cardiac surgery. Case Presentation: A 50-year-old Chinese woman received elective double metal valve replacement, including the aortic valve and the mitral valve, under cardiopulmonary bypass (CPB) and suffered severe septic shock on postoperative day (PD) 30. Through the detection of PB19-specific nucleic acids in blister fluid and serum samples via metagenomic next-generation sequencing (mNGS), positive serum PB19 IgM and no other proven infection, acute PB19 infection was confirmed. After five days of combined treatment, no further fever or abdominal discomfort was noted, and the patient's circulation gradually became stable without vasoactive medications. Conclusion: PB19 may be an unrecognized cause of septic shock, rash, fever of unknown origin or multiple systemic signs and symptoms, especially in immunosuppressed and immunocompetent critically ill patients. Investigations for viral aetiology are needed.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Eritema Infeccioso , Parvovirus B19 Humano , Choque Séptico , Femenino , Humanos , Persona de Mediana Edad , Eritema Infeccioso/complicaciones , Choque Séptico/etiología , Choque Séptico/complicaciones , Parvovirus B19 Humano/genética , Anticuerpos Antivirales
20.
Reprod Biomed Online ; 46(4): 673-685, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36894359

RESUMEN

RESEARCH QUESTION: What are the effects of alpha-ketoglutarate (α-KG) treatment on the ovarian morphology and ovarian reserve function of rats with cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI)? DESIGN: Thirty female Sprague Dawley rats were randomly allocated to a control group (n = 10) and a POI group (n = 20). Cyclophosphamide was administered for 2 weeks to induce POI. The POI group was then divided into two groups: a CTX-POI group (n = 10), administered normal saline, and a CTX-POI + α-KG group (n = 10), administered α-KG 250 mg/kg per day for 21 days. Body mass and fertility was assessed at the end of the study. Serum samples were collected for hormone concentration measurement, and biochemical, histopathological, TUNEL, immunohistochemical and glycolytic pathway analyses were conducted for each group. RESULTS: The α-KG treatment increased body mass and ovarian index of rats, partially normalized their disrupted estrous cycles, prevented follicular loss, restored ovarian reserve, and increased pregnancy rate and litter sizes of rats with POI. It significantly reduced serum concentration of FSH (P < 0.001), increased that of oestradiol (P<0.001) and reduced apoptosis of granulosa cells (P = 0.0003). Moreover, α-KG increased concentrations of lactate (P = 0.015) and ATP (P = 0.025), reduced that of pyruvate (P<0.001) and increased expression of rate-limiting enzymes of glycolysis in the ovary. CONCLUSIONS: α-KG treatment ameliorates the deleterious effects of CTX on the fertility of female rats, possibly by reducing the apoptosis of ovarian granulosa cells and restoring glycolysis.


Asunto(s)
Menopausia Prematura , Insuficiencia Ovárica Primaria , Embarazo , Humanos , Ratas , Femenino , Animales , Ácidos Cetoglutáricos/efectos adversos , Ratas Sprague-Dawley , Insuficiencia Ovárica Primaria/terapia , Ciclofosfamida/efectos adversos , Apoptosis
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