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1.
J Transl Med ; 21(1): 225, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36978075

RESUMEN

BACKGROUND: Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. METHODS: In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. RESULTS: After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. CONCLUSIONS: We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Animales , Ratones , Receptores Quiméricos de Antígenos/metabolismo , Neoplasias/terapia , Inmunoterapia Adoptiva/métodos , Inmunoterapia , Citocinas/metabolismo , Macrófagos/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral
2.
BMC Health Serv Res ; 23(1): 460, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37161474

RESUMEN

BACKGROUND: Elderly patients with chronic diseases are very vulnerable during the transition from hospital to home and have a high need for transitional care. The quality of transitional care is closely related to patient health outcomes. Using appropriate scales to evaluate the quality of transitional care is important for efforts aimed at improving it. The study aimed to analyze the consistency between the Chinese version of the Partners at Care Transitions Measure (PACT-M) and the Care Transition Measure (CTM) in assessing the quality of transition care in elderly patients with chronic diseases. METHODS: This is a cross-sectional study, we used a convenience sampling method to investigate patients with chronic diseases aged ≧ 65 years who were about to be discharged from the three affiliated hospitals of Zhengzhou University in Henan Province, from August 2021 to May 2022. The sample consisted of 196 elderly patients with chronic diseases. Data were collected using a demographic survey, PACT-M, and CTM. We used EpiData 3.1 software for systematic logical error checking, SPSS 21.0 to analyze the data, and the Bland-Altman analysis to analyze the consistency of the two scales. RESULTS: The mean total scores for PACT-M and CTM were 65.52 ± 6.23 and 52.07 ± 7.26, respectively. The 95% confidence interval (CI) for the mean difference and ratios were (-31.52, 4.61) and (0.85, 1.72), with 3.57% and 5.10% of the points outside the 95% CI limits, separately. CONCLUSIONS: The difference analysis of Bland-Altman showed a good consistency of the two scales, while the rate analysis did not meet the a priori definition of good consistency, but it is very close to 5%. Therefore, the consistency of the two scales in assessing the quality of transitional care for elderly patients with chronic diseases needs to be further validated.


Asunto(s)
Pueblo Asiatico , Enfermedad Crónica , Cuidado de Transición , Anciano , Humanos , Estudios Transversales , Hospitales , Alta del Paciente
3.
Phys Chem Chem Phys ; 24(29): 17716-17722, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35838540

RESUMEN

Immigration to Mars, which is expected to be powered mainly by photovoltaics, is one of the greatest dreams of humanity. However, the extreme temperature difference and high-energy cosmic radiation on the surface of Mars make it difficult for conventional photovoltaics to operate steadily over time. With their advantages of being lightweight, having a high irradiation tolerance, and an outstanding power conversion efficiency (PCE), perovskite solar cells (PSCs) have shown themselves to be a promising candidate for Martian applications. In this study, we simulated the low-intensity-low-temperature (LILT) environment of the Mars surface, and monitored the in situ device performance of PSCs. Surprisingly, the device PCE was not only maintained at a high level but was even improved slightly. Further investigation revealed that the self-healing effect of perovskites under LILT conditions could be attributed to the light-induced decomposition of the perovskite film and the ß-phase perovskite recrystallization process at the perovskite/hole transport layer interface. Interfacial ß-phase perovskites are stable at low temperatures, which can facilitate charge extraction and protect the perovskite bulk from long-term light damage. This study demonstrated the feasibility of PSCs and provides a reference for Martian applications.

4.
BMC Health Serv Res ; 22(1): 1132, 2022 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-36071481

RESUMEN

BACKGROUND: Post-traumatic hydrocephalus (PTH) is a complication of traumatic brain injury (TBI) that requires treatment and postoperative care. The shunt is one of the main treatments for PTH, which presents with dysfunction and infection. Considering brain injury, hydrocephalus shunt malfunction, and infection, family caregivers need to be responsible for caring for PTH patients, recognizing shunt malfunction and infection, and managing those patients accordingly from hospital to home. Understanding the experiences and needs of caregivers is beneficial for knowing their competency and quality of health care, ameliorating and ensuring future transition care. The study aimed to explore the feelings, experiences, and needs of family caregivers when caring for patients with TBI, PTH and shunts. METHODS: This was exploratory research of a purposive sample of 12 family caregivers of adult patients with TBI, PTH and shunts in five neurosurgery departments at a general hospital in Zhengzhou, Henan Province, China, using a semi-structured interview method. Data were collected from October 2021 to March 2022 before being analyzed by content analysis methods. RESULTS: Caregivers required professional and social knowledge and support in the areas of TBI, PTH and shunts, caregiving interventions, psychological care needs, and health insurance, just as caregivers do, but unlike other general caregivers, care for patients with TBI, PTH, and shunt is fraught with uncertainty and the need to manage shunt setting, and caregivers often experience 'complex emotional reaction' during the transitional period, where care needs and complex emotions may lead to a lack of caregiver confidence, which in turn may affect caregiving behaviors, and experiences that affect care may be mediated through caregiving confidence. The perceived availability of resources, particularly those that are still available to them when they return home, has a significant impact on participants' emotional response and sense of confidence. CONCLUSIONS: The emotional response and the impact of stressor caregivers after TBI, PTH, and shunt was important, and sometimes confidence in care appeared to be an intermediate and useful factor that needed to be considered as health professionals prepared to develop care resources on how to manage and empower patients with TBI, PTH, and shunt. Meanwhile, there may be gaps and inequities in supportive care for patients diagnosed with TBI, PTH, and shunt in China.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Hidrocefalia , Adulto , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/psicología , Cuidadores/psicología , Transición del Hospital al Hogar , Humanos , Hidrocefalia/cirugía , Investigación Cualitativa
5.
BMC Health Serv Res ; 21(1): 1284, 2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34844597

RESUMEN

BACKGROUND: The Partners at Care Transitions Measure (PACT-M) is a measure that assesses the quality and safety of care during the transition from hospital to home from the patient's perspective. The aim of this study was to examine the psychometric properties of the Chinese version of the PACT-M in Mainland China. METHODS: This was a cross-sectional study. A convenience sample of patients was recruited from three tertiary hospitals affiliated with Zhengzhou University, China. A total of 402 participants were interviewed before discharge, and 306 participants were interviewed one month after discharge from hospital to home using the Chinese version of the PACT-M. The statistical methods used in this study include the critical ratio value, item total correlation, test-retest, Cronbach's alpha, confirmatory factor analysis and exploratory factor analysis. RESULTS: The Chinese version of the PACT-M consists of PACT-M1 and PACT-M2, both of which have two dimensions, the number of items in both parts are consistent with the original English language version. The Cronbach's alpha values of the PACT-M1 and PACT-M2 were 0.802 and 0.741, and the test-retest reliability values were 0.885 and 0.837. The item content validity index and scale content validity index values of the PACT-M1 and PACT-M2 were all 1.0. CONCLUSION: The Chinese version of the PACT-M shows acceptable validity and reliability and can be used to assess the quality and safety of transitional care from hospital to home from the patient's perspective in mainland China.


Asunto(s)
Lenguaje , Transferencia de Pacientes , China , Estudios Transversales , Análisis Factorial , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
6.
J Biol Chem ; 294(14): 5643-5656, 2019 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-30723163

RESUMEN

In all eukaryotes, a functional mitotic spindle is essential for distributing duplicated chromosomes into daughter cells. Mitotic spindle assembly involves highly ordered arrangement of microtubules (MTs). The Augmin protein complex recruits γ-tubulin ring complex (γ-TuRC) to MTs and thereby promotes MT-based MT nucleation and mitotic spindle assembly. However, several factors that may promote Augmin recruitment to MTs remain unknown. Here, we show that echinoderm microtubule-associated protein-like 3 (EML3), an MT-associated protein, facilitates binding between MTs and Augmin/γ-TuRC and recruiting the latter to MTs for proper mitotic spindle assembly and kinetochore-MT connections. Using immunofluorescence microscopy, live-cell imaging, and immunoprecipitation assays, we found that EML3 recruits Augmin/γ-TuRC to the MTs to enhance MT-based MT nucleation in both spindle and small acentrosomal asters. We also noted that the EML3-mediated recruitment is controlled by cyclin-dependent kinase 1 (CDK1), which phosphorylated EML3 at Thr-881 and promoted its binding to Augmin/γ-TuRC. RNAi-mediated EML3 knockdown in HeLa cells reduced spindle localization of Augmin/γ-TuRC, which resulted in abnormal spindle assembly and caused kinetochore-MT misconnection. The introduction of exogenous WT or a Thr-881 phosphorylation mimic EML3 variant into the EML3 knockdown cells restored normal Augmin/γ-TuRC localization and spindle assembly. The EML3 knockdown also affected the spindle assembly checkpoint, delaying chromosome congression and cell division. Taken together, our results indicate that EML3 regulates mitotic spindle assembly and the kinetochore-MT connection by regulating MT-based MT nucleation and recruiting Augmin/γ-TuRC to MTs.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Cinetocoros/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/metabolismo , Huso Acromático/metabolismo , Sustitución de Aminoácidos , Proteínas de Ciclo Celular/genética , Técnicas de Silenciamiento del Gen , Células HEK293 , Células HeLa , Humanos , Proteínas Asociadas a Microtúbulos/genética , Microtúbulos/genética , Mutación Missense , Huso Acromático/genética , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
7.
Biomacromolecules ; 21(4): 1351-1367, 2020 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-32202418

RESUMEN

Chitosan (CS), a natural biopolymer, has been extensively explored for multiple applications including tissue engineering, gene therapy, bioimaging, and sewage treatment due to its abundant availability, intrinsic biocompatibility, biodegradability, and tunable biological properties. Nevertheless, the actual use of CS is limited because of its water-insolubility in physiological circumstances, which could be optimized by chemical modifications via active side groups. Etherification is one of the most widely used reactions to obtain water-soluble CS derivatives, such as hydroxybutyl CS (HBC). HBC, synthesized by grafting hydroxybutyl groups to the functional hydroxyl and amino groups of CS skeleton, has been demonstrated to possess superior biological properties over those of CS, especially satisfactory water solubility in neutral condition and reversible stimulus-response against external heat. Meanwhile, the unique characteristics of thermally sensitive "sol-gel" and "sol-micelle" transition have gained tremendous attention, which differ in heterogeneously and homogeneously synthesized HBC. Herein, we discuss the synthesis (heterogeneously and homogeneously) of HBC, favorable physiochemical properties of HBC, and HBC-centered biocomposites in a range of formulations or dosage forms such as sponges, gels, nanoparticles, nanofibers, and films. Meanwhile, we summarize the potential bioapplications and trends of HBC and HBC centered biocomposites and offer our perspectives on the plausible advances in this field in the near future.


Asunto(s)
Quitosano , Nanofibras , Nanopartículas , Quitosano/análogos & derivados , Ingeniería de Tejidos
8.
Phys Chem Chem Phys ; 20(11): 7395-7400, 2018 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-29508866

RESUMEN

Planar perovskite solar cells (PSCs) have gained great interest due to their low-temperature solution preparation and simple process. In inverted planar PSCs, an additional buffer layer is usually needed on the top of the PCBM electron-transport layer (ETL) to enhance the device performance. In this work, we used a new buffer layer, zirconium acetate (Zr(Ac)4). The inclusion of the Zr(Ac)4 buffer layer leads to the increase of FF from ∼68% to ∼79% and PCE from ∼14% to ∼17% in the planar PSCs. The UPS measurement indicates that the Zr(Ac)4 layer has a low HOMO level of -8.2 eV, indicating that the buffer layer can act as a hole-blocking layer. Surface morphology and surface chemistry investigations reveal that the elements I, MA and Pb can diffuse across the PCBM ETL, damaging the device performance. The covering Zr(Ac)4 molecules fill in the pinholes of the PCBM layer and effectively block the ions/molecules of the perovskite from diffusion across the ETL. The resulting more robust PCBM/Zr(Ac)4 ETL leads to weaker ionic charge accumulation and lower diode leakage current. The double role of hole-and-ion blocking of the Zr(Ac)4 layer explains the improved FF and PCE in the PSCs.

9.
Phys Chem Chem Phys ; 20(31): 20732, 2018 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-30042987

RESUMEN

Correction for 'Improved fill factor in inverted planar perovskite solar cells with zirconium acetate as the hole-and-ion-blocking layer' by Xuewen Zhang et al., Phys. Chem. Chem. Phys., 2018, 20, 7395-7400.

10.
Biomed Chromatogr ; 32(10): e4302, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29809276

RESUMEN

Periplocin is a cardiac glycoside and has been used widely in the clinic for its cardiotonic, anti-inflammatory and anti-tumor effects. Although it is taken frequently by oral administration in the clinic, there have been no reports demonstrating that periplocin could be detected in vivo after an oral administration, so there is an urgen need to determine the characteristics of periplocin in vivo after oral administration. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated to identify and quantify periplocin and its two metabolites in rat tissue after a single dosage of perplocin at 50 mg/kg. The results demonstrated that periplocin and its two metabolites were detected in all of the selected tissues; periplocin could reach peak concentration quickly after administration, while periplocymarin and periplogenin reached maximum concentration > 4.83 h after administration. The tissue distribution of analytes tended to be mostly in the liver, and higher analyte concentrations were found in the heart, liver, spleen, lung and kidney, but a small amount of chemical constituents was distributed into the brain. The consequences obtained using this method might provide a meaningful insight for clinical investigations and applications.


Asunto(s)
Cromatografía Liquida/métodos , Saponinas/análisis , Saponinas/farmacocinética , Espectrometría de Masas en Tándem/métodos , Animales , Glicósidos Cardíacos/análisis , Glicósidos Cardíacos/química , Glicósidos Cardíacos/farmacocinética , Digitoxigenina/análogos & derivados , Digitoxigenina/análisis , Digitoxigenina/química , Digitoxigenina/farmacocinética , Modelos Lineales , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Saponinas/administración & dosificación , Saponinas/química , Sensibilidad y Especificidad , Distribución Tisular
11.
Molecules ; 23(7)2018 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-29986486

RESUMEN

Epimedium herb is one of the most vital traditional Chinese medicines (TCMs), which is used for "nourishing the kidney and reinforcing the Yang". In the guidance of TCM theory, Epimedium herb is usually processed with lamb oil to increase its efficacy. The contents of active ingredients in different Epimedium are significantly varied, which may derive from their different species, regions and processing methods. In this research, 13 batches of raw Epimedium collected from 6 provinces were identified. After optimization of the processing method of Epimedium, a liquid chromatography⁻mass spectrometry (LC⁻MS/MS) method for simultaneous determination of 16 compounds was established to evaluate the quality of raw and processed. Then the multivariate statistical technique was applied to compare different batches of Epimedium based on the LC⁻MS/MS data. As a conclusion, the herbs collected from 6 areas were ascribed to 5 species by microscopic and appearance features. Meanwhile, all of the raw and processed samples were classified by partial least squares discriminant analysis (PLS-DA) based on the 16 analyzed compounds. The comparison results indicate that processing and species both have important influences on Epimedium compositions contents.


Asunto(s)
Medicamentos Herbarios Chinos/análisis , Epimedium/química , Epimedium/clasificación , Cromatografía Líquida de Alta Presión , Análisis de los Mínimos Cuadrados , Extractos Vegetales/análisis , Análisis de Componente Principal , Espectrometría de Masas en Tándem
12.
Molecules ; 23(6)2018 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-29857519

RESUMEN

A rapid and reliable HPLC-MS/MS method has been developed and validated for the simultaneous quantification of twelve bioactive compounds (baohuoside II, baohuoside I, sagittatoside A, sagittatoside B, magnoflorine, epimedin A, epimedin B, epimedin C, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and icariin) in rat plasma. The collected plasma samples were prepared by protein precipitate with acetonitrile. The twelve compounds were separated on a CORTECS®C18 column (4.6 mm × 150 mm, 2.7 µm) with a gradient mobile phase system of 0.1% (v/v) formic acid and acetonitrile at a flow rate of 0.3 mL/min. All of the analytes were quantitated using electrospray ionization (ESI) in negative ion mode with selected reaction monitoring (SRM). The intra- and inter-day accuracy ranged from -5.6% to 13.0%, and the precisions of the analytes were less than 10.9%. The mean recoveries of the analytes were in the range of 60.66% to 99.77% and the matrix effect ranged from 93.08% to 119.84%. Stability studies proved that the analytes were stable under the tested conditions, with a relative standard deviation (RSD) lower than 11.7%. The developed method was successfully applied to evaluating the pharmacokinetic study of twelve bioactive compounds after oral administration of Epimedium extract in rat.


Asunto(s)
Cromatografía Líquida de Alta Presión , Epimedium/química , Fitoquímicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Espectrometría de Masas en Tándem , Animales , Estabilidad de Medicamentos , Masculino , Estructura Molecular , Ratas , Reproducibilidad de los Resultados
13.
Mol Pain ; 122016.
Artículo en Inglés | MEDLINE | ID: mdl-27175014

RESUMEN

BACKGROUND: The N-methyl-D-aspartate subtype of glutamate receptor plays a critical role in morphine tolerance. D-serine, a co-agonist of N-methyl-D-aspartate receptor, participates in many physiological and pathophysiological processes via regulating N-methyl-D-aspartate receptor activation. The purinergic P2X7 receptor activation can induce the D-serine release in the central nervous system. This study aimed to investigate the role of the ventrolateral midbrain periaqueductal gray D-serine in the mechanism of morphine tolerance in rats. The development of morphine tolerance was induced in normal adult male Sprague-Dawley rats through subcutaneous injection of morphine (10 mg/kg). The analgesic effect of morphine (5 mg/kg, i.p.) was assessed by measuring mechanical withdrawal thresholds in rats with an electronic von Frey anesthesiometer. The D-serine concentration and serine racemase expression levels in the ventrolateral midbrain periaqueductal gray were evaluated through enzyme-linked immunosorbent assay and Western blot analysis, respectively. The effects of intra-ventrolateral midbrain periaqueductal gray injections of the D-serine degrading enzyme D-amino acid oxidase and antisense oligodeoxynucleotide targeting the P2X7 receptor on chronic morphine-treated rats were also explored. RESULTS: We found that repeated morphine administrations decreased the antinociceptive potency of morphine evidenced by the percent changes in mechanical pain threshold in rats. By contrast, the D-serine contents and the expression levels of the serine racemase protein were upregulated in the ventrolateral midbrain periaqueductal gray in morphine-tolerant rats. The development of morphine tolerance was markedly alleviated by intra-ventrolateral midbrain periaqueductal gray injections of D-amino acid oxidase or antisense oligodeoxynucleotide targeting the P2X7 receptor. CONCLUSIONS: Our data indicate that the development of antinociceptive tolerance to morphine is partially mediated by ventrolateral midbrain periaqueductal gray D-serine content, and the activation of the ventrolateral midbrain periaqueductal gray P2X7 receptor is an essential prelude to D-serine release. These results suggest that a cascade involving P2X7 receptor-D-serine-N-methyl-D-aspartate receptor mediated signaling pathway in the supraspinal mechanism of morphine tolerance.


Asunto(s)
Tolerancia a Medicamentos , Morfina/farmacología , Sustancia Gris Periacueductal/metabolismo , Serina/metabolismo , Analgesia , Animales , D-Aminoácido Oxidasa/metabolismo , Masculino , Microinyecciones , Morfina/administración & dosificación , Oligodesoxirribonucleótidos/farmacología , Umbral del Dolor/efectos de los fármacos , Racemasas y Epimerasas/metabolismo , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7/metabolismo , Regulación hacia Arriba/efectos de los fármacos
14.
Phys Chem Chem Phys ; 17(15): 9613-8, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25772648

RESUMEN

The accumulation of mobile ions causes space charge at interfaces in perovskite solar cells. There is a slow dynamic process of ion redistribution when the bias is changed. The interface charge affects band bending and thus the photocurrent of the solar cells. Consequently the dynamic process of the interface charge governs the current-voltage hysteresis. Very low interface charge density leads to hysteresis-free devices.

15.
J Cell Biol ; 223(2)2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38117947

RESUMEN

Precise chromosome congression and segregation requires the proper assembly of a steady-state metaphase spindle, which is dynamic and maintained by continuous microtubule flux. NuSAP is a microtubule-stabilizing and -bundling protein that promotes chromosome-dependent spindle assembly. However, its function in spindle dynamics remains unclear. Here, we demonstrate that NuSAP regulates the metaphase spindle length control. Mechanistically, NuSAP facilitates kinetochore capture and spindle assembly by promoting Eg5 binding to microtubules. It also prevents excessive microtubule depolymerization through interaction with Kif2A, which reduces Kif2A spindle-pole localization. NuSAP is phosphorylated by Aurora A at Ser-240 during mitosis, and this phosphorylation promotes its interaction with Kif2A on the spindle body and reduces its localization with the spindle poles, thus maintaining proper spindle microtubule flux. NuSAP knockout resulted in the formation of shorter spindles with faster microtubule flux and chromosome misalignment. Taken together, we uncover that NuSAP participates in spindle assembly, dynamics, and metaphase spindle length control through the regulation of microtubule flux and Kif2A localization.


Asunto(s)
Segregación Cromosómica , Cinesinas , Proteínas Asociadas a Microtúbulos , Huso Acromático , Humanos , Células HeLa , Cinesinas/genética , Cinesinas/metabolismo , Cinetocoros/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/genética , Microtúbulos/metabolismo , Mitosis , Huso Acromático/genética , Huso Acromático/metabolismo
16.
Front Pharmacol ; 15: 1401826, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055489

RESUMEN

Pomegranate seeds (PS) are the dried seeds derived from pomegranate fruit, accounting for approximately 20% of the fruit's total weight, and are a by-product of pomegranate juice extraction. These seeds hold significance in traditional medicine among Uyghurs and Tibetan cultures, featuring diverse clinical applications within traditional Chinese medicine. These applications include management of gastric coldness and acidity, abdominal distension, liver and gallbladder fever, and pediatric enteritis. PS demonstrates properties such as stomach tonicity, qi regulation, analgesia, and anti-inflammatory effects. Extensive research underscores the richness of PS in various phytochemical compounds and metabolites, notably unsaturated fatty acids (particularly linolenic acid and linoleic acid), phenolic compounds tocopherols, proteins, and volatile oils. Notably, among these bioactive compounds, punicic acid (PA), found within PS, demonstrates potential in the prevention and treatment of cancers, diabetes, obesity, and other ailments. Despite extensive literature on pomegranate as a botanical entity, a comprehensive review focusing specifically on the chemical composition and pharmacological effects of PS remains elusive. Therefore, this review aimed to consolidate knowledge regarding the medicinal properties of PS, summarizing its chemical composition, traditional uses, and pharmacological effects in treating various diseases, thereby laying a foundation for the advancement and application of PS in the field of pharmacology.

17.
Adv Clin Exp Med ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591347

RESUMEN

BACKGROUND: Over the past few decades, thyroid cancer (TC) incidence has steadily increased globally. The most common TC is human papillary thyroid carcinoma (PTC), which is poorly responsive to the current treatments. Hence, finding a successful therapeutic is urgently required. OBJECTIVES: Bergapten (BG) is a furanocoumarin, a natural psoralen derivative isolated from numerous species of citrus and bergamot oil that has demonstrated anti-tumor activity. However, there are no reports available on the efficacy of BG on PTC cells. MATERIAL AND METHODS: The current research investigated the anti-cancer activity of BG on human BCPAP cells, with cytotoxicity and apoptosis evaluated using MTT assay, AO/EB, DAPI, PI, ELISA, mRNA, and western blot. RESULTS: Bergapten (control group, 10 µM/mL and 15 µM/mL) inhibited PTC cell proliferation and stimulated apoptosis by enhancing Bax and caspase and reducing Bcl-2, cyclin-D1, c-myc, and survivin in a dose-dependent manner. Furthermore, BG expressively attenuated PI3K/AKT/GSK-3ß signaling, creating an uneven Bax/Bcl-2 ratio that triggered Cyt-c, caspase cascade and apoptosis in human PTC cells. CONCLUSIONS: Our findings emphasize that BG has the potential to be used as a protective natural remedy for human PTC cells.

18.
Sci China Life Sci ; 67(9): 1957-1969, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38763998

RESUMEN

Proper function of the centromeres ensures correct attachment of kinetochores to spindle microtubules and faithful chromosome segregation in mitosis. Defects in the integrity and function of centromeres can result in chromosome missegregation and genomic instability. Bub1 is essential for the mitotic centromere dynamics, yet the underlying molecular mechanisms remain largely unclear. Here, we demonstrate that TIP60 acetylates Bub1 at K424 and K431 on kinetochores in early mitosis. This acetylation increases the kinase activity of Bub1 to phosphorylate centromeric histone H2A at T120 (H2ApT120), which recruits Aurora B and Shugoshin 1 (Sgo1) to regulate centromere integrity, protect centromeric cohesion, and ensure the subsequent faithful chromosome segregation. Expression of the non-acetylated Bub1 mutant reduces its kinase activity, decreases the level of H2ApT120, and disrupts the recruitment of centromere proteins and chromosome congression, leading to genomic instability of daughter cells. When cells exit mitosis, HDAC1-regulated deacetylation of Bub1 decreases H2ApT120 levels and thereby promotes the departure of centromeric CPC and Sgo1, ensuring timely centromeres disassembly. Collectively, our results reveal a molecular mechanism by which the acetylation and deacetylation cycle of Bub1 modulates the phosphorylation of H2A at T120 for recruitment of Aurora B and Sgo1 to the centromeres, ensuring faithful chromosome segregation during mitosis.


Asunto(s)
Aurora Quinasa B , Centrómero , Segregación Cromosómica , Histona Acetiltransferasas , Histonas , Proteínas Serina-Treonina Quinasas , Humanos , Acetilación , Aurora Quinasa B/metabolismo , Aurora Quinasa B/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Centrómero/metabolismo , Inestabilidad Genómica , Células HeLa , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética , Histonas/metabolismo , Cinetocoros/metabolismo , Mitosis , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética
19.
Artículo en Inglés | MEDLINE | ID: mdl-38657181

RESUMEN

Due to their unique afterglow ability, long-wavelength-light rechargeable persistent luminescence (PersL) nanoparticles (PLNPs) have been emerging as an important category of imaging probes. Among them, ZnGa2O4:0.6% Cr3+ (ZGC) PLNPs have gained widespread recognition due to the ease of synthesis and uniform morphology. Unfortunately, the limited absorption arising from the low molar extinction coefficient of Cr3+ results in relatively low afterglow intensity and rapid decay after long-wavelength LED light irradiation. Herein, we discovered a strategy that boosting dye-sensitization performance was able to effectively amplify the PersL signal under white LED light. Specifically, Dil served as a highly efficient sensitizer for Cr3+, promoting the absorption of the excitation light. By adjusting the Pr dopant concentrations, ZGCP0.5 PLNPs with optimal trap densities were obtained, which showed the highest PersL intensity and dye-sensitized performance. Strikingly, ZGCP0.5-Dil PLNPs exhibited a 24.3-fold enhancement in intensity and a 2-fold prolongation of decay time over bare ZGC PLNPs through the synergy effect of optimal electron traps and dye sensitization. Photostable ZGCP0.5-Dil PLNPs enabled imaging of the HepG2 tumor and effectively guided tumor surgical resection verified by the H&E staining analysis. This strategy could be a significant reference in other dye-sensitization PLNPs to enhance longer-wavelength rechargeable PersL.

20.
J Mater Chem B ; 12(35): 8655-8661, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39082116

RESUMEN

Surgical resection remains the main treatment for malignant tumors. Image-guided surgery aims to remove tumor tissue completely while preserving normal tissue, thereby reducing tumor recurrence rates and injury. However, challenges like tissue autofluorescence, limited probe penetration and low contrast restrict its use. Near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) provide a solution by emitting persistent luminescence (PersL) even after excitation ceases, thus circumventing autofluorescence and enabling deep tumor imaging. In this study, we prepared nano-sized (140 nm hydrodynamic size) Cr3+ doped zinc gallogermanate (ZGC) using a removable template method and modified it with folate acid to obtain ZGC-FA, which exhibits NIR (695 nm) PersL with a signal-to-noise ratio of 23.9 in vivo. We utilized a colon cancer model that selectively expressed luciferase for the first time to validate the guiding efficacy of ZGC-FA in precision surgical resection. Post-intraperitoneal injection at 50 minutes, the PersL closely matched the tumor boundaries, achieving an overlap rate of approximately 98%. Complete tumor resection was achieved under PersL guidance, with only 2.3% of healthy tissue removed. This research underscores the potential of ZGC-FA in the field of surgical oncology. The precision of the ZGC-FA guided surgical approach holds promise to enhance surgical outcomes and facilitate postoperative recovery in patients.


Asunto(s)
Neoplasias Colorrectales , Nanopartículas , Nanopartículas/química , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Humanos , Animales , Ratones , Cirugía Asistida por Computador/métodos , Luminiscencia , Tamaño de la Partícula , Imagen Óptica , Ácido Fólico/química , Sustancias Luminiscentes/química , Ratones Endogámicos BALB C , Ratones Desnudos , Propiedades de Superficie
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