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1.
Proc Natl Acad Sci U S A ; 121(37): e2403038121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226359

RESUMEN

Proteostasis and genomic integrity are respectively regulated by the endoplasmic reticulum-associated protein degradation (ERAD) and DNA damage repair signaling pathways, with both pathways essential for carcinogenesis and drug resistance. How these signaling pathways coordinate with each other remains unexplored. We found that ER stress specifically induces the DNA-PKcs-regulated nonhomologous end joining (NHEJ) pathway to amend DNA damage and impede cell death. Intriguingly, sustained ER stress rapidly decreased the activity of DNA-PKcs and DNA damage accumulated, facilitating a switch from adaptation to cell death. This DNA-PKcs inactivation was caused by increased KU70/KU80 protein degradation. Unexpectedly, the ERAD ligase HRD1 was found to efficiently destabilize the classic nuclear protein HDAC1 in the cytoplasm, by catalyzing HDAC1's polyubiquitination at lysine 74, at a late stage of ER stress. By abolishing HDAC1-mediated KU70/KU80 deacetylation, HRD1 transmits ER signals to the nucleus. The resulting enhanced KU70/KU80 acetylation provides binding sites for the nuclear E3 ligase TRIM25, resulting in the promotion of polyubiquitination and the degradation of KU70/KU80 proteins. Both in vitro and in vivo cancer models showed that genetic or pharmacological inhibition of HADC1 or DNA-PKcs sensitizes colon cancer cells to ER stress inducers, including the Food and Drug Administration-approved drug celecoxib. The antitumor effects of the combined approach were also observed in patient-derived xenograft models. These findings identify a mechanistic link between ER stress (ERAD) in the cytoplasm and DNA damage (NHEJ) pathways in the nucleus, indicating that combined anticancer strategies may be developed that induce severe ER stress while simultaneously inhibiting KU70/KU80/DNA-PKcs-mediated NHEJ signaling.


Asunto(s)
Daño del ADN , Proteína Quinasa Activada por ADN , Estrés del Retículo Endoplásmico , Ubiquitina-Proteína Ligasas , Animales , Humanos , Ratones , Línea Celular Tumoral , Reparación del ADN por Unión de Extremidades , Reparación del ADN , Proteína Quinasa Activada por ADN/metabolismo , Proteína Quinasa Activada por ADN/genética , Retículo Endoplásmico/metabolismo , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 1/genética , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Proteolisis , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación
2.
Plants (Basel) ; 13(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39273892

RESUMEN

Cryopreservation, storing biological material in liquid nitrogen (LN, -196 °C), offers a valuable option for the long-term conservation of non-orthodox seeds and vegetatively propagated species in the sector of agrobiodiversity and wild flora. Although the large-scale cryobanking of germplasm collections has been increasing worldwide, the wide application of cryopreservation protocols in wild flora is hampered by difficulties in vitro propagation and a lack of universal cryopreservation protocols, among others. This study established a systematic approach to developing an in vitro culture and droplet-vitrification cryopreservation procedure for shoot tips of Scrophularia kakudensis. The standard procedure includes a two-step preculture with 10% sucrose for 31 h and with 17.5% sucrose for 16 h, osmoprotection with loading solution C4-35% (17.5% glycerol + 17.5% sucrose, w/v) for 30 min, cryoprotection with A3-80% (33.3% glycerol + 13.3% dimethyl sulfoxide + 13.3% ethylene glycol + 20.1% sucrose, w/v) at 0 °C for 60 min, and cooling and rewarming using aluminum foil strips. After unloading, a three-step regrowth procedure starting with an ammonium-free medium with growth regulators was essential for developing normal plantlets from cryopreserved shoot tips. Liquid overlay on the gelled medium two weeks after inoculation resulted in vigorous growth during subcultures. Moreover, liquid overlay increased LN regeneration by up to 80%, i.e., 23% higher than no liquid overlay.

3.
Materials (Basel) ; 17(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39274795

RESUMEN

This study employs a hybrid numerical-experimental calibration method based on phenomena to determine the fracture parameters of the Modified Mohr-Coulomb (MMC) model. Using a self-developed VUMAT subroutine and the element deletion technique, the fracture process of a wide plate pipeline is thoroughly analyzed. This study investigates the impact of various crack shapes on the fracture response under tensile loading and the influence of surface crack size on the initiation location of a wide plate. These results demonstrate the calibrated MMC fracture model's accurate prediction of the toughness fracture behavior of X80 pipeline steel. Under equal area conditions of the dangerous section, circular cracks exhibit lower bearing capacity compared to elliptical cracks. Elliptical cracks predominantly propagate in the thickness direction, whereas circular cracks show nearly uniform growth in all directions. Furthermore, when the crack depth is less than half of the wall thickness, the damage accumulation value at the midpoint of the crack front is maximized; conversely, when the crack front is closer to the internal measurement point of the wide plate, the damage accumulation value is maximized.

4.
J Oral Implantol ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39231395

RESUMEN

With the population aging, the proportion of elderly individuals is expected to increase, and the proportion of individuals over 80 is also likely to increase. Given that the population is aging and life expectancy is increasing, elderly patients who have lost thei teeth will also increase. Impaired masticatory function caused by tooth loss is a risk factor for cognitive decline and frailty, and neglecting to treat tooth loss is a critical issue. In this report, five patients over 80 requested dental implants for new missing teeth and underwent immediate implant placement. All patients were treated by the same surgeon using the same technique, materials, and dental implants. Five elements were measured for the peri-implant bone from the cone-beam computed tomography images. All patients were followed for three or more years and exhibited good progress without any abnormal findings in their oral cavities or notable radiographic abnormalities such as bone absorption or peri-implantitis. Compared to conventional treatment with delayed placement, combining immediate implant placement and regenerative medicine for fixed superstructures may be the better option for missing tooth replacement if the conditions are suitable. Thus, this treatment modality may improve the quality of life in elderly patients, especially super elderly patients.

5.
Curr Genet ; 70(1): 15, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235627

RESUMEN

Chromatin remodelling complexes (CRC) are ATP-dependent molecular machines important for the dynamic organization of nucleosomes along eukaryotic DNA. CRCs SWI/SNF, RSC and INO80 can move positioned nucleosomes in promoter DNA, leading to nucleosome-depleted regions which facilitate access of general transcription factors. This function is strongly supported by transcriptional activators being able to interact with subunits of various CRCs. In this work we show that SWI/SNF subunits Swi1, Swi2, Snf5 and Snf6 can bind to activation domains of Ino2 required for expression of phospholipid biosynthetic genes in yeast. We identify an activator binding domain (ABD) of ATPase Swi2 and show that this ABD is functionally dispensable, presumably because ABDs of other SWI/SNF subunits can compensate for the loss. In contrast, mutational characterization of the ABD of the Swi2-related ATPase Sth1 revealed that some conserved basic and hydrophobic amino acids within this domain are essential for the function of Sth1. While ABDs of Swi2 and Sth1 define separate functional protein domains, mapping of an ABD within ATPase Ino80 showed co-localization with its HSA domain also required for binding actin-related proteins. Comparative interaction studies finally demonstrated that several unrelated activators each exhibit a specific binding pattern with ABDs of Swi2, Sth1 and Ino80.


Asunto(s)
Adenosina Trifosfatasas , Ensamble y Desensamble de Cromatina , Proteínas de Unión al ADN , Unión Proteica , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Factores de Transcripción , Activación Transcripcional , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ensamble y Desensamble de Cromatina/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Regulación Fúngica de la Expresión Génica , Dominios Proteicos , Proteínas Nucleares , Proteínas de Ciclo Celular , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
6.
Biotechnol Lett ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235648

RESUMEN

Rotifers are small, ubiquitous invertebrate animals found throughout the world and have emerged as a promising model system for studying molecular mechanisms in the fields of experimental ecology, aquatic toxicology, and geroscience. However, the lack of efficient gene expression manipulation techniques has hindered the study of rotifers. In this study, we used the L4440 plasmid with two reverse-oriented T7 promoters, along with RNase-deficient E. coli HT115, to efficiently produce dsRNA and thereby present an efficient feeding-based RNAi method in Brachionus plicatilis. We targeted Bp-Ku70 & Ku80, key proteins in the DNA double-strand breaks repair pathway, and then subjected rotifers to UV radiation. We found that the mRNA expression, fecundity, as well as survival rate diminished significantly as a result of RNAi. Overall, our results demonstrate that the feeding-based RNAi method is a simple and efficient tool for gene knockdown in B. plicatilis, advancing their use as a model organism for biological research.

7.
Eur J Surg Oncol ; 50(12): 108650, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39244977

RESUMEN

BACKGROUND: The suitability of radical surgery for very elderly pancreatic cancer (PC) patients remains controversial due to concerns about postoperative functional reserve. Inflammatory-nutritional status may help identify elderly patients at risk of compromised postoperative treatment tolerance. METHODS: This retrospective analysis included 121 patients over eighty who were diagnosed with PC in 2010-2019, 40 of whom underwent radical surgery. Surgical outcomes were compared with those of 205 younger patients (under 80 years-old) who underwent radical surgery. K-means cluster analysis was conducted with four inflammatory-nutritional indices (NLR, PLR, PNI, and mGPS) to define, and the indices using ordinal logistic analysis were evaluated in each cluster to create a formula named 'nutritional index (NTI)', which was then used to redefine the clusters. The predictive ability of the NTI was validated in other octogenarians who underwent pancreatectomy for PC between 2020 and 2023. RESULTS: Patients older than eighty exhibited comparable overall survival to younger patients (median survival time, 30.7/37.1 months, p = 0.20). However, octogenarian-plus patients had lower rates of adjuvant chemotherapy (AC) initiation (45/80 %) and treatment upon recurrence (52/84 %), resulting in shorter survival after recurrence (7.4/11.1 months, p = 0.06). Inflammatory-nutritional status was significantly associated with overall survival, with poor nutritional status being linked to lower rates of AC initiation and/or treatment upon recurrence. NTI effectively predicted AC feasibility. CONCLUSIONS: Radical surgery for octogenarian-plus PC patients meeting the current criteria was safe, but lower rates of postoperative treatment initiation may lead to poorer outcomes after recurrence. Inflammatory-nutritional status assessment could enhance surgical eligibility in octogenarian-plus PC patients.

8.
Front Cell Dev Biol ; 12: 1394531, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39228401

RESUMEN

DNA-protein crosslinks pose a significant challenge to genome stability and cell viability. Efficient repair of DPCs is crucial for preserving genomic integrity and preventing the accumulation of DNA damage. Despite recent advances in our understanding of DPC repair, many aspects of this process, especially at the organismal level, remain elusive. In this study, we used zebrafish as a model organism to investigate the role of TDP2 (Tyrosyl-DNA phosphodiesterase 2) in DPC repair. We characterized the two tdp2 orthologs in zebrafish using phylogenetic, syntenic and expression analysis and investigated the phenotypic consequences of tdp2 silencing in zebrafish embryos. We then quantified the effects of tdp2a and tdp2b silencing on cellular DPC levels and DSB accumulation in zebrafish embryos. Our findings revealed that tdp2b is the main ortholog during embryonic development, while both orthologs are ubiquitously present in adult tissues. Notably, the tdp2b ortholog is phylogenetically closer to human TDP2. Silencing of tdp2b, but not tdp2a, resulted in the loss of Tdp2 activity in zebrafish embryos, accompanied by the accumulation of DPCs and DSBs. Our findings contribute to a more comprehensive understanding of DPC repair at the organismal level and underscore the significance of TDP2 in maintaining genome stability.

9.
Geriatr Nurs ; 60: 42-51, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217841

RESUMEN

Prior to this cross-sectional study, the intrinsic capacity (IC) loss rates and protective factors in nursing homes for individuals aged 80 and older remained unexplored. Analysing 434 participants, this study found 86.9 % of individuals experienced the loss of at least one IC domain, with detailed losses in locomotion, vision, vitality, hearing, psychological, and cognitive capacities at rates of 83.2 %, 52.8 %, 50.9 %, 46.5 %, 44.9 %, and 44.0 %, respectively. Following latent class analysis (LCA), five distinct IC impairment patterns were noted, with locomotor impairment emerging as a central component across most classes. IC protective factors for persons aged 80 years and older included financial stability, being male or younger within the cohort, junior high school or higher education, being married, no smoking history, manageable comorbidity levels, minimal medication use, good sleep, and not using assistive devices. Based on these five classes, this study provides a potential practical framework alongside recommendations for IC care strategies in the oldest-old, emphasising the importance of locomotor function in maintaining the overall IC.

10.
EFSA J ; 22(8): e8952, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39099619

RESUMEN

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL-no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL-no: 10.057] was evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL-no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL-no: 10.057]. However, for the flavouring substance [FL-no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL-no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.

11.
Heliyon ; 10(14): e34095, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39113962

RESUMEN

This research presents a new group of mathematical functions connected to Bernoulli's Lemniscate, using the q-derivative. Expanding on previous studies, the research concentrates on determining coefficient approximations, the Fekete-Szego functional, Zalcman inequality, Krushkal inequality, along with the second and third Hankel determinants for this recently established collection of functions. Additionally, the study derives the Fekete-Szego inequality for the function ξ f ( ξ ) and obtains the inverse function f - 1 ( ξ ) for this specific class. This research advances our understanding in this area and suggests for further exploration.

12.
EFSA J ; 22(8): e8960, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39104808

RESUMEN

The EFSA Panel on Food Contact Materials (FCM) assessed the safety of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt', used as additives up to 0.3% in polyethylene terephthalate (PET), polyamide (PA), thermoplastic polyurethane (TPU), polylactic acid (PLA) and poly(vinyl chloride) (PVC) in contact with all food types for long-term storage at room temperature and below, after hot-fill and/or heating. The substances consist of the chemical classes wax esters, carboxylic acids, alcohols and calcium salts of acids, along with an unidentified organic fraction up to ■■■■■ w/w. Migration into 10% ethanol and 4% acetic acid was below 0.012 mg/kg for each chemical class, and about 0.001 mg/kg for the unidentified fraction. In isooctane, migration was up to 0.297 mg/kg food for wax esters, below 0.01 mg/kg food for the other chemical classes and about 0.02 mg/kg food for the unidentified fraction. The contact with dry food and food simulated by 20% ethanol were considered covered by the migration tests with aqueous simulants. Based on genotoxicity assays and compositional analyses, the constituents of the chemical classes did not raise a concern for genotoxicity. The potential migration of individual constituents or groups of chemically-related compounds of the unidentified fraction would result in exposures below (for aqueous food) and above (for fatty food) the threshold of toxicological concern for genotoxic carcinogens. Therefore, the FCM Panel concluded that the substances are not of safety concern for the consumer, if used as additives up to 0.3% w/w in PET, PLA and rigid PVC materials and articles intended for contact with all food types except for fatty foods, for long-term storage at room temperature and below, including hot-fill and/or heating up to 100°C for up to 2 h.

13.
Sci Rep ; 14(1): 18142, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103411

RESUMEN

The impact of adding ethylene vinyl acetate copolymer (EVA 80) and 1 wt% TiO2 nanoparticles on the morphology and crystallization behavior of poly(lactic acid) blends was investigated using DSC, SEM, and POM. Thermal analysis revealed the enhancement of crystallinity of PLA in the presence of TiO2 and higher EVA 80 content in the blend. The PLA and EVA 80 components showed compatibility, as evidenced by the shift of the glass transition temperatures of the PLA phase in the blend to lower values compared to neat PLA. The lower temperature shift of the cold crystallization of the PLA and the formation of the small spherulites of the PLA in the blends indicated that the EVA 80 and TiO2 act as a nucleating agent for crystallization. The non-isothermal crystallization parameters of the composites were evaluated using Avrami's modified model, the MO approach, and Friedman's isoconversional method. The Avrami's modified rate constant (K) and the effective activation energy values significantly increased with the incorporation of EVA 80 and TiO2 nanoparticles. Furthermore, the thermogravimetric analysis (TGA) showed improved thermal stability of PLA by adding EVA 80 and TiO2.

14.
J Xenobiot ; 14(3): 1093-1108, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39189177

RESUMEN

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39174496

RESUMEN

BACKGROUND: Peutz-Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development. OBJECTIVE: This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps. METHODS: Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes. RESULTS: Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid-derived suppressor cells (MDSCs). CONCLUSION: The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

16.
Macromol Biosci ; : e2400196, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177156

RESUMEN

Electrospinning is a technique used to create nano/micro-fibrous materials from various polymers for biomedical uses. Polymers like polycaprolactone (PCL) are commonly used, but their hydrophobic properties can limit their applications. To enhance hydrophilicity, nonionic surfactants such as sorbitane monooleate (Span80) and poloxamer (P188) can be added to the PCL electrospinning solution without altering its net charge density. These additions enable the successful production of PCL/P188 and PCL/Span80 fibrous substrates. In this study, P188 and Span80 are incorporated into the PCL solutions; they are successfully electrospun into PCL/P188 and PCL/Span80 substrates, respectively. PCL/P188 substrates show that until a specific P188 concentration, fiber and pore sizes are similar to PCL substrates. However, exceeding 0.30% P188 concentration enlarges fibers, impacting fiber uniformity at higher concentrations. Conversely, higher concentrations of Span80 result in thicker, less uniform fibers, indicating potential disruptions in the electrospinning process. Notably, both surfactants significantly improve substrate hydrophilicity, enhancing the adhesion and proliferation of fibroblasts, endothelial cells, and smooth muscle cells. P188, in particular, shows superior efficacy in promoting cell adhesion and growth at concentrations optimized for different cell types. Therefore, precise surfactant concentrations in the electrospinning solution can lead to the optimization of electrospun substrates for tissue engineering applications.

17.
Biomed Pharmacother ; 178: 117287, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39137652

RESUMEN

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.


Asunto(s)
Suplementos Dietéticos , Inositol , Ratones Endogámicos C57BL , Animales , Masculino , Ratones , Administración Oral , Inositol/farmacología , Inositol/administración & dosificación , Litio/administración & dosificación , Litio/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/prevención & control , Arritmias Cardíacas/tratamiento farmacológico , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Cardiopatías/patología , Cardiopatías/tratamiento farmacológico
18.
J Pharm Pract ; : 8971900241273241, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137364

RESUMEN

Background: Amiodarone-induced anaphylaxis is seldom reported. The mechanism of this anaphylaxis is unknown. Methods: A literature search was carried out with keywords "Amiodarone" and "Anaphylaxis" and "polysorbate 80" or "hypotension." A search using "amiodarone" in the FDA Adverse Event Reporting System (FAERS) from 1969 to 2024 was also conducted. Results: There are a total of 10 cases of amiodarone-induced anaphylaxis in the literature. Six patients were male. Ages ranged from 15 to 86 years old. Nine cases were triggered by intravenous injection (IV) and one by oral administration. Eight patients did not have previous exposure to amiodarone. The trigger times for IV amiodarone were immediate to 90 minutes. All nine cases of IV amiodarone resulted in hypotension (90%), with an immeasurable blood pressure (70%). Presentations included bronchospasm or a skin rash (60%), angioedema (40%), and unconsciousness (20%). Only one patient had a history of allergy to penicillin and sulfonamide. An amiodarone skin test was positive on one patient. Increased blood tryptase (4 cases), positive basophil activation test to amiodarone (2 cases), increased eosinophil count (1 case), and increased serum IgE (1 case) were reported. Amiodarone was terminated in 80% of the patients. Epinephrine, norepinephrine, antihistamine-1, or steroids were used to rescue patients. Four patients were intubated. All patients fully recovered. In the FAERS database, 89 cases of amiodarone-associated anaphylaxis were reported, resulting in 14 deaths. Conclusions: Solvent polysorbate 80, amiodarone, and iodide may contribute to amiodarone-induced anaphylaxis. Prompt treatment is the key to saving patients.

19.
Artículo en Inglés | MEDLINE | ID: mdl-39138905

RESUMEN

BACKGROUND: Selenium is a trace element crucial for thyroid function, and has potential therapeutic benefits in Graves' orbitopathy (GO). Therefore, we aim to evaluate its efficacy and safety in GO patients to provide valuable insights into its role as a therapeutic option for this condition. DESIGN: Systematic review and meta-analysis. PATIENTS: GO Patients treated with selenium compared to placebo. MEASUREMENTS: Clinical activity score (CAS), Graves' orbitopathy quality of life (GO-QOL), eye symptoms and signs, and adverse events. RESULTS: Out of 1684 records screened, four randomised controlled trials were included. Selenium was superior at 6 months in lowering the CAS (MD = -1.27, 95% confidence interval [CI] [-1.68, -0.85], p < .0001]), improving total GO-QOL (RR = 2.54, 95% CI [1.69-3.81], p < .00001), and improving the visual and the psychological functioning scores (MD = 10.84, 95% CI [4.94-16.73], p = .003), (MD = 12.76, 95% CI [8.51-17.00], p < .00001) respectively. Similarly, it significantly improved these outcomes at 12 months. It also showed a significant decrease in the palpebral aperture at 6 months (MD = -1.49, 95% CI [-2.90, -0.08], p = .04). However, no significant differences were observed in proptosis, soft tissue involvement, ocular motility, and adverse effects. CONCLUSIONS: Selenium is effective in reducing CAS and improving the palpebral aperture and GO-QOL in patients with GO. Additionally, it is safe and has promising therapeutic implications. However, further research is needed to validate its long-term efficacy and safety.

20.
J Colloid Interface Sci ; 677(Pt A): 885-894, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39126807

RESUMEN

Zinc metal anodes encounter significant challenges, including dendrite growth, hydrogen evolution, and corrosion, all of which impede the rate capability and longevity of aqueous zinc-ion batteries (AZIBs). To effectively tackle these issues, we introduced Tween-80 into the traditional ZnSO4 electrolyte as an additive. Tween-80 possesses electronegative oxygen atoms that enable it to adsorb onto the zinc (Zn) anode surface, facilitating the directional deposition of Zn metal along the (002) orientation. The hydroxyl and ether groups within Tween-80 can displace some of the coordinated water molecules in the Zn2+ inner solvation shell. This disruption of the hydrogen bond network regulates the solvation structure of Zn2+ ions and suppresses the possibility of hydrogen evolution. Moreover, the long hydrocarbon chain present in Tween-80 exhibits excellent hydrophobic properties, aiding in the resistance against corrosion of the Zn anode by water molecules and reducing hydrogen evolution. Consequently, a symmetric cell equipped with the Tween-80 additive can cycle stably for over 4000 h at 1 mA cm-2 and 1 mA h cm-2. When paired with the V2O5 cathode, the full cell demonstrates a high-capacity retention rate exceeding 80 % over 1000 cycles at a current density of 2 A g-1. This study underscores the advantages of utilizing non-ionic surfactants for achieving high-performance aqueous zinc-ion batteries.

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