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1.
Nanomicro Lett ; 16(1): 194, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743294

RESUMEN

Aqueous zinc-ion batteries (AZIBs) are one of the most compelling alternatives of lithium-ion batteries due to their inherent safety and economics viability. In response to the growing demand for green and sustainable energy storage solutions, organic electrodes with the scalability from inexpensive starting materials and potential for biodegradation after use have become a prominent choice for AZIBs. Despite gratifying progresses of organic molecules with electrochemical performance in AZIBs, the research is still in infancy and hampered by certain issues due to the underlying complex electrochemistry. Strategies for designing organic electrode materials for AZIBs with high specific capacity and long cycling life are discussed in detail in this review. Specifically, we put emphasis on the unique electrochemistry of different redox-active structures to provide in-depth understanding of their working mechanisms. In addition, we highlight the importance of molecular size/dimension regarding their profound impact on electrochemical performances. Finally, challenges and perspectives are discussed from the developing point of view for future AZIBs. We hope to provide a valuable evaluation on organic electrode materials for AZIBs in our context and give inspiration for the rational design of high-performance AZIBs.

2.
Adv Sci (Weinh) ; : e2310239, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582519

RESUMEN

Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor-Acceptor (D-A) bipolar polymer with n-type pyrene-4,5,9,10-tetraone unit storing Li cations and p-type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium-ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D-A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g-1 at 200 mA g-1, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g-1 at 10 A g-1 and a noteworthy energy density up to 554 Wh kg-1. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.

3.
Curr Protoc ; 4(4): e1025, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38600839

RESUMEN

Cardiac fibroblasts (CF) are an essential cell type in cardiac physiology, playing diverse roles in maintaining structural integrity, extracellular matrix (ECM) synthesis, and tissue repair. Under normal conditions, these cells reside in the interstitium in a quiescent state poised to sense and respond to injury by synthesizing and secreting collagen, vimentin, hyaluronan, and other ECM components. In response to mechanical and chemical stimuli, these "resident" fibroblasts can undergo a transformation through a continuum of activation states into what is commonly known as a "myofibroblast," in a process critical for injury response. Despite progress in understanding the contribution of fibroblasts to cardiac health and disease, much remains unknown about the signaling mediating this activation, in part owing to technical challenges in evaluating CF function and activation status in vitro. Given their role in monitoring the ECM, CFs are acutely sensitive to stiffness and pressure. High basal activation of isolated CFs is common due to the super-physiologic stiffness of traditional cell culture substrates, making assays dependent on quiescent cells challenging. To overcome this problem, cell culture parameters must be tightly controlled, and the use of dishes coated with biocompatible reduced-stiffness substrates, such as 8-kPa polydimethylsiloxane (PDMS), has shown promise in reducing basal activation of fibroblasts. Here, we describe cell culture protocol for maintaining CF quiescence in vitro to enable a dynamic range for the assessment of activation status in response to fibrogenic stimuli using PDMS-coated coverslips. Our protocol provides a cost-effective tool to study fibroblast signaling and activity, allowing researchers to better understand the underlying mechanisms involved in cardiac fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of 8-kPa polydimethylsiloxane (PDMS)/gelatin-coated coverslips for cardiac fibroblast cell culture Basic Protocol 2: Isolation of adult cardiac fibroblasts and plating onto PDMS coverslips Basic Protocol 3: Assessment of cardiac fibroblast activation by α smooth muscle actin (αSMA) immunocytochemistry.


Asunto(s)
Fibroblastos , Corazón , Fibroblastos/metabolismo , Miofibroblastos/metabolismo , Transducción de Señal , Dimetilpolisiloxanos/metabolismo , Dimetilpolisiloxanos/farmacología
4.
J Biomed Sci ; 31(1): 42, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38650023

RESUMEN

BACKGROUND: Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear. METHODS: Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs. RESULTS: The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+-Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups. CONCLUSION: Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.


Asunto(s)
Arritmias Cardíacas , Miocarditis , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Animales , Ratas , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Furanos/farmacología , Indenos , Miocarditis/metabolismo , Miocarditis/fisiopatología , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Sulfonamidas/farmacología , Remodelación Ventricular/efectos de los fármacos , Remodelación Ventricular/fisiología
5.
Toxics ; 12(4)2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38668527

RESUMEN

The sweet potato weevil Cylas formicarius is a notorious underground pest in sweet potato (Ipomoea batatas L.). However, little is known about the effects of cadmium (Cd) stress on weevil biology and resistance to pesticides and biotic agents. Therefore, we fed sweet potato weevils with Cd-contaminated sweet potato and assessed adult food intake and survival and larval developmental duration and mortality rates, as well as resistance to the insecticide spinetoram and susceptibility to the entomopathogenic fungus Beauveria bassiana. With increasing Cd concentration, the number of adult weevil feeding holes, adult survival and life span, and larval developmental duration decreased significantly, whereas larval mortality rates increased significantly. However, at the lowest Cd concentration (30 mg/L), adult feeding was stimulated. Resistance of adult sweet potato weevils to spinetoram increased at low Cd concentration, whereas Cd contamination did not affect sensitivity to B. bassiana. Thus, Cd contamination affected sweet potato weevil biology and resistance, and further studies will investigate weevil Cd accumulation and detoxification mechanisms.

6.
J Reconstr Microsurg ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38593991

RESUMEN

BACKGROUND: Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. METHODS: We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. RESULTS: In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p < 0.001) compared to those without AF or new-onset AF. CONCLUSION: Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

7.
Injury ; 55(6): 111568, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38669890

RESUMEN

IMPORTANCE: Most patients use a traditional socket prosthesis (TSP) to ambulate independently following transtibial amputation. However, these patients generally require prosthesis repairs more than twice annually and an entirely new prosthesis every two years. Furthermore, transtibial amputation patients have four times the skin ulceration rate of transfemoral patients, prompting more frequent prosthesis refitting and diminished use. Trans-Tibial osseointegration (TTOI) is a promising technique to address the limitations of TSP, but remains understudied with only four cohorts totaling 41 total procedures reported previously. Continued concerns regarding the risk of infection and questions as to functional capacity postoperatively have slowed adoption of TTOI worldwide. OBJECTIVE: This study reports the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TTOI following traumatic amputation. DESIGN: Retrospective observational cohort study. The cohort consisted of patients with data outcomes collected before and after osseointegration intervention. SETTING: A large, tertiary referral, major metropolitan center. PARTICIPANTS: Twenty-one skeletally mature adults who had failed socket prosthesis rehabilitation, with at least two years of post-osseointegration follow-up. MAIN OUTCOMES AND MEASURES: Mobility was evaluated by K-level, Timed Up and Go (TUG), and Six Minute Walk Test (6MWT). QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and Short Form 36 (SF36). Adverse events included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure. RESULTS: All patients demonstrated statistically significant improvement post osseointegration surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF36 Physical Component Score (p < 0.01 for all). Three patients had four unplanned surgeries: two soft tissue refashionings, and one soft tissue debridement followed eventually by implant removal. No deaths, postoperative systemic complications, more proximal amputations, or periprosthetic fractures occurred. CONCLUSIONS AND RELEVANCE: TTOI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic transtibial amputation. Adverse events are relatively infrequent and not further disabling. Judicious use of TTOI seems reasonable for properly selected patients. LEVEL OF EVIDENCE: 2 (Therapeutic investigation, Observational study with dramatic effect).


Asunto(s)
Amputación Traumática , Miembros Artificiales , Oseointegración , Calidad de Vida , Tibia , Humanos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Amputación Traumática/cirugía , Amputación Traumática/rehabilitación , Estudios de Seguimiento , Tibia/cirugía , Resultado del Tratamiento , Diseño de Prótesis , Implantación de Prótesis
8.
Materials (Basel) ; 17(6)2024 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-38541530

RESUMEN

In order to examine the mechanical properties and rotational bending fatigue performance of 40CrNi2MoE steel subsequent to tempering at varying temperatures, the steel specimen was subjected to tempering within the range of 400~460 °C. SEM, EBSD, and TEM were used to analyze the microstructure as well as precipitates. The strain hardening law was studied using the modified Crussard-Jaoult method. Investigations were undertaken to reveal the rotational bending fatigue life with respect to the tempering temperature. The findings indicate that the strength and fatigue life of the examined steels exhibit a decline as the tempering temperature increases, with the primary factor affecting this trend being the alteration in dislocation density. No notable impact on the fatigue fracture morphology exerted by tempering temperature was found within the range of the experiment. The C-J model analysis reveals that the work-hardening behavior of the trial steels is influenced by dislocations and the second phase.

9.
Int J Biol Sci ; 20(3): 1093-1109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38322119

RESUMEN

Background: As lung cancer is the leading cause of cancer death worldwide, the development of new medicines is a crucial endeavor. Naringenin, a flavanone derivative, possesses anti-cancer and anti-inflammatory properties and has been reported to have cytotoxic effects on various cancer cells. The current study investigated the underlying molecular mechanism by which naringenin induces cell death in lung cancer. Methods: The expression of apoptosis, cell cycle arrest, and autophagy markers in H1299 and A459 lung cancer cells was evaluated using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL), Western blot, Annexin V/PI stain, PI stain, acridine orange staining, and transmission electron microscopy (TEM). Using fluorescence microscopy, DALGreen was used to observe the degradation of p62, a GFP-LC3 plasmid was used to evaluate puncta formation, and a pcDNA3-GFP-LC3-RFP-LC3ΔG plasmid was used to evaluate autophagy flux. Furthermore, the anti-cancer effect of naringenin was evaluated in a subcutaneous H1299 cell xenograft model. Results: Naringenin treatment of lung cancer cells (H1299 and A459) reduced cell viability and induced cell cycle arrest. Pretreatment of cells with ROS scavengers (N-acetylcysteine or catalase) suppressed the naringenin-induced cleavage of apoptotic protein and restored cyclin-dependent kinase activity. Naringenin also triggered autophagy by mediating ROS generation, thereby activating AMP-activated protein kinase (AMPK) signaling. ROS inhibition not only inhibited naringenin-induced autophagic puncta formation but also decreased the ratio of microtubule-associated proteins 1A/1B light chain 3 II (LC3II)/LC3I and activity of the AMPK signaling pathway. Furthermore, naringenin suppressed tumor growth and promoted apoptosis in the xenograft mouse model. Conclusion: This study demonstrated the potent anti-cancer effects of naringenin on lung cancer cells, thereby providing valuable insights for developing small-molecule drugs that can induce cell cycle arrest, apoptosis, and autophagic cell death.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Flavanonas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Apoptosis , Neoplasias Pulmonares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular , Autofagia , Flavanonas/farmacología
10.
J Nat Prod ; 87(2): 252-265, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38294199

RESUMEN

Eleven new steroidal alkaloids, along with nine known related compounds, were isolated from the bulbs of Fritillaria sinica. Seven pairs of diastereomers were identified, including six and four 20-deoxy cevanine-type steroidal alkaloid diastereomers with molecular weights of 413 and 415, respectively. Structures were elucidated based on spectroscopic data analysis, chemical derivatization, and single-crystal X-ray diffraction analysis. Compounds 5, 9, 11, 12, 16, and 20 exhibited significant in vitro cytotoxic activity against non-small-cell lung cancer with CC50 values from 6.8 ± 3.9 to 12 ± 5 µM.


Asunto(s)
Alcaloides , Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Fritillaria , Neoplasias Pulmonares , Humanos , Fritillaria/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estructura Molecular , Neoplasias Pulmonares/tratamiento farmacológico , Alcaloides/química , Esteroides/química
11.
ChemSusChem ; 17(4): e202301809, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38230562

RESUMEN

Dual-ion batteries based on organic electrodes show great potential to break through the bottlenecks existed in conventional LIBs due to their high specific capacity, lifted working voltage, and environmental benignity. Herein, two innovative viologen-based bipolar copolymers poly(viologen-pyrene-4,5,9,10-tetrone dichloride) (PVPTOCl2 ) and poly(viologen-anthraquinone dichloride) (PVAQCl2 ) were synthesized and applied as high performance cathodes for lithium-dual-ion battery. Bearing the dual-ion storage capability of viologen and carbonyls, as well as the conjugated structure of pyrene-4,5,9,10-tetrone, the synthesized copolymers show remarkable electrochemical performances for LIBs. Compared to PVAQCl2 , PVPTOCl2 shows superior electrochemical performance with high initial specific capacity (235.0 mAh g-1 at 200 mA g-1 ), high reversibility (coulombic efficiency up to 99.96 % at 1 A g-1 ), excellent rate performance (150.3 mAh g-1 at 5 A g-1 ) and outstanding cycling stability (a reversible capacity of 197.5 mAh g-1 at a current density of 1 A g-1 and a low capacity loss per cycle of 0.11‰ during 3000 cycles). Moreover, the charge storage mechanism was systematically investigated by ex-situ FT-IR, ex-situ XPS and DFT calculations. The results clearly reveal the structure-property relationship of the bipolar-molecules, providing a new platform to develop efficient bipolar materials for dual-ion batteries.

12.
Asian J Surg ; 47(4): 1763-1768, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38212227

RESUMEN

OBJECTIVE: To identify risk factors associated with adverse airway events (AAEs) in primary oral cancer patients undergoing tumor ablation followed by free tissue transfer without prophylactic tracheostomy. METHODS: We retrospectively collected primary oral cancer patients who underwent tumor ablation surgery following free-tissue transfer without prophylactic tracheostomy during February 2017 to June 2019 in Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan. 379 patients were included. Data were analysed from 2020 to 2021. Demographics, comorbidities, intraoperative variables and postoperative respiration profile were obtained from the medical record. Main outcome was postoperative AAEs, including requirement of endotracheal intubation after extubation and tracheostomy after prolonged intubation. RESULTS: Of the 379 patients, postoperative AAEs happened in 29 patients (7.6 %). In reintubation group, patients were older with more diabetes mellitus, hypertension and cerebrovascular disease. These patients had lower preoperative hemoglobin, creatinine, and albumin level with more intraoperative blood transfusion. In postoperative respiration profile, rapid shallow breathing index (RSBI) and PaO2/FiO2 (PF) ratio were poorer. On multivariate analysis, patient's age, tumor location, and cross-midline segmental mandibulectomy and a lower PF ratio were independent risk factors for postoperative AAEs. CONCLUSIONS: In head and neck cancer patients that underwent tumor ablation followed by free tissue transfer without prophylactic tracheostomy, patient's age, tumor location, cross-midline segmental mandibulectomy and P/F ratio are associated with postoperative AAEs.


Asunto(s)
Neoplasias de la Boca , Traqueostomía , Humanos , Estudios Retrospectivos , Factores de Riesgo , Intubación Intratraqueal , Neoplasias de la Boca/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control
13.
Transl Res ; 268: 1-12, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38244770

RESUMEN

Interleukin (IL)-33, a cytokine involved in immune responses, can activate its receptor, suppression of tumorigenicity 2 (ST2), is elevated during atrial fibrillation (AF). However, the role of IL-33/ST2 signaling in atrial arrhythmia is unclear. This study explored the pathological effects of the IL-33/ST2 axis on atrial remodeling and arrhythmogenesis. Patch clamping, confocal microscopy, and Western blotting were used to analyze the electrical characteristics of and protein activity in atrial myocytes (HL-1) treated with recombinant IL-33 protein and/or ST2-neutralizing antibodies for 48 hrs. Telemetric electrocardiographic recordings, Masson's trichrome staining, and immunohistochemistry staining of the atrium were performed in mice receiving tail vein injections with nonspecific immunoglobulin (control), IL-33, and IL-33 combined with anti-ST2 antibody for 2 weeks. IL-33-treated HL-1 cells had a reduced action potential duration, lower L-type Ca2+ current, greater sarcoplasmic reticulum (SR) Ca2+ content, increased Na+/Ca2+ exchanger (NCX) current, elevation of K+ currents, and increased intracellular calcium transient. IL-33-treated HL-1 myocytes had greater activation of the calcium-calmodulin-dependent protein kinase II (CaMKII)/ryanodine receptor 2 (RyR2) axis and nuclear factor kappa B (NF-κB) / NLR family pyrin domain containing 3 (NLRP3) signaling than did control cells. IL-33 treated cells also had greater expression of Nav1.5, Kv1.5, NCX, and NLRP3 than did control cells. Pretreatment with neutralizing anti-ST2 antibody attenuated IL-33-mediated activation of CaMKII/RyR2 and NF-κB/NLRP3 signaling. IL-33-injected mice had more atrial ectopic beats and increased AF episodes, greater atrial fibrosis, and elevation of NF-κB/NLRP3 signaling than did controls or mice treated with IL-33 combined with anti-ST2 antibody. Thus, IL-33 recombinant protein treatment promotes atrial remodeling through ST2 signaling. Blocking the IL-33/ST2 axis might be an innovative therapeutic approach for patients with atrial arrhythmia and elevated serum IL-33.


Asunto(s)
Remodelación Atrial , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Miocitos Cardíacos , Interleucina-33/metabolismo , Animales , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Remodelación Atrial/efectos de los fármacos , Ratones , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Transducción de Señal , Masculino , Ratones Endogámicos C57BL , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/metabolismo , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/patología , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/metabolismo , Línea Celular , Potenciales de Acción/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo
14.
J Cancer ; 15(4): 1041-1052, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38230224

RESUMEN

Background: Dopamine receptors have been reported to be involved in pain, while the exact effects and mechanism in bone cancer pain have not been fully explored. Methods: Bone cancer pain model was created by implanting walker 256 mammary gland carcinoma into right tibia bone cavity. Primary cultured spinal neurons were used for in vitro evaluation. FLIPR, western-blot, immunofluorescence, and Co-IP were used to detect cell signaling pathway. Results: Our results indicated that spinal dopamine D1 receptor (D1DR) and spinal dopamine D2 receptor (D2DR) could form heteromers in TCI rats, and antagonizing spinal D1DR and D2DR reduced heteromers formation and alleviated TCI-induced bone cancer pain. Further results indicated that D1DR or D2DR antagonist induced antinociception in TCI rats could be reversed by D1DR, D2DR, and D1/D2DR heteromer agonists. And Gq, IP3, and PLC inhibitors also attenuated TCI-induced bone cancer pain. In vitro results indicated that D1DR or D2DR antagonist decreased the Ca2+ oscillations upregulated by D1DR, D2DR, and D1/D2DR heteromer agonists in activated primary cultured spinal neurons. Moreover, inhibition of D1/D2DR heteromers induced antinociception in TCI rats was partially mediated by the CaMKII and MAPKs pathway. In addition, a natural compound levo-Corydalmine (l-CDL), could inhibit D1/D2DR heteromers and attenuate bone cancer pain. Results: Inhibition of spinal D1/D2DR heteromers via l-CDL decreases excitability in spinal neurons, which might present new therapeutic strategy for bone cancer pain.

15.
Small ; : e2308748, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282458

RESUMEN

The upconversion luminescence (UCL) in the second near-infrared window (NIR-II) is highly attractive due to its excellent performance in high-resolution bioimaging, anticounterfeiting, and temperature sensing. However, upconvertion nanoparticles (UCNPs) are normally emitted in visible light, potentially impacting the imaging quality. Here, a monochromatic Er3+ -rich (NaErF4 :x%Yb@NaYF4 ) nanoparticles with excitation at 1532 nm and emission at 978 nm is proposed, both situated in the NIR-II region. The proper proportion of Yb3+ ions doping has a positive effect on the NIR-II emission, by enhancing the cross relaxation efficiency and accelerating the energy transfer rate. Owing to the interaction between the Er3+ and Yb3+ is inhibited at low temperatures, the UCL emission intensities at visible and NIR-II regions show opposite trend with temperature changing, which establishes a fitting formula to derive temperature from the luminous intensity ratio, promoting the potential application of UCL in NIR-II regions for the temperature sensing.

16.
Fundam Clin Pharmacol ; 38(2): 262-275, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37664898

RESUMEN

BACKGROUND: Metabolic stress predisposes to ventricular arrhythmias and sudden cardiac death. Right ventricular outflow tract (RVOT) is the common origin of ventricular arrhythmias. Adenosine monophosphate-regulated protein kinase (AMPK) activation is an important compensatory mechanism for cardiac remodeling during metabolic stress. OBJECTIVES: The purpose of this study was to access whether AMPK inhibition would modulate RVOT electrophysiology, calcium (Ca2+ ) regulation, and RVOT arrhythmogenesis or not. METHODS: Conventional microelectrodes were used to record electrical activity before and after compound C (10 µM, an AMPK inhibitor) in isoproterenol (1 µM)-treated rabbit RVOT tissue preparations under electrical pacing. Whole-cell patch-clamp and confocal microscopic examinations were performed in baseline and compound C-treated rabbit RVOT cardiomyocytes to investigate ionic currents and intracellular Ca2+ transients in isolated rabbit RVOT cardiomyocytes. RESULTS: Compound C decreased RVOT contractility, and reversed isoproterenol increased RVOT contractility. Compound C decreased the incidence, rate, and duration of isoproterenol-induced RVOT burst firing under rapid pacing. Compared to baseline, compound C-treated RVOT cardiomyocytes had a longer action potential duration, smaller intracellular Ca2+ transients, late sodium (Na+ ), peak L-type Ca2+ current density, Na+ -Ca2+ exchanger, transient outward potassium (K+ ) current, and rapid and slow delayed rectifier K+ currents. CONCLUSION: AMPK inhibition modulates RVOT electrophysiological characteristics and Ca2+ homeostasis, contributing to lower RVOT arrhythmogenic activity. Accordingly, AMPK inhibition might potentially reduce ventricular tachyarrhythmias.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Calcio , Animales , Conejos , Calcio/metabolismo , Adenosina Monofosfato , Isoproterenol/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Arritmias Cardíacas/tratamiento farmacológico , Miocitos Cardíacos/metabolismo , Homeostasis , Potenciales de Acción
17.
Phytomedicine ; 123: 155228, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38006808

RESUMEN

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.


Asunto(s)
Fritillaria , Plantas Medicinales , Fritillaria/química , Cromatografía en Capa Delgada , Plantas Medicinales/química , Control de Calidad , Análisis Espectral , Metabolómica
19.
J Chromatogr A ; 1714: 464544, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38142618

RESUMEN

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.


Asunto(s)
Bupleurum , Medicamentos Herbarios Chinos , Ácido Oleanólico , Saponinas , Medicamentos Herbarios Chinos/química , Bupleurum/química , Extractos Vegetales , Saponinas/análisis , Ácido Oleanólico/análisis , Cromatografía Liquida , Espectrometría de Masas , Iones , Cromatografía Líquida de Alta Presión/métodos
20.
Small ; : e2307180, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38054789

RESUMEN

Despite the unique advantages of single-atom catalysts, molecular dual-active sites facilitate the C-C coupling reaction for C2 products toward the CO2 reduction reaction (CO2 RR). The Ni/Cu proximal dual-active site catalyst (Ni/Cu-PASC) is developed, which is a harmonic catalyst with dual-active sites, by simply mixing commercial Ni-phthalocyanine (Ni-Pc) and Cu-phthalocyanine (Cu-Pc) molecules physically. According to scanning transmission electron microscopy (STEM) and transmission electron microscopy (TEM) energy dispersive spectroscopy (EDS) data, Ni and Cu atoms are separated, creating dual-active sites for the CO2 RR. The Ni/Cu-PASC generates ethanol with an FE of 55%. Conversely, Ni-Pc and Cu-Pc have only detected single-carbon products like CO and HCOO- . In situ X-ray absorption spectroscopy (XAS) indicates that CO generation is caused by the stable Ni active site's balanced electronic state. The CO production from Ni-Pc consistently increased the CO concentration over Cu sites attributed to subsequent reduction reaction through a C-C coupling on nearby Cu. The CO bound (HCOO- ) peak, which can be found on Cu-Pc, vanishes on Ni/Cu-PASC, as shown by in situ fourier transformation infrared (FTIR). The characteristic intermediate of *CHO instead of HCOO- proves to be the prerequisite for multi-carbon products by electrochemical CO2 RR. The work demonstrates that the harmonic dual-active sites in Ni/Cu-PASC can be readily available by the cascading proximal active Ni- and Cu-Pc sites.

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