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1.
J Palliat Med ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968345

RESUMEN

Background: Despite the global acceptance of palliative sedation, China's engagement in this field remains comparatively restricted. There exists a scarcity of information regarding the attitudes and experiences of hospice nurses concerning palliative sedation. Objectives: This survey aimed at investigating the attitudes of Chinese hospice nurses toward palliative sedation, as well as their practices in palliative sedation. Design: A cross-sectional descriptive study. Setting/Subjects: In 2023, the survey on palliative sedation was introduced during the opening ceremony of the largest National Symposium on New Advances in Hospice Nursing in China. Subsequently, the study questionnaire was disseminated through email to a cohort of 806 hospice nurses attending the conference. Measurements/Results: The statistical analysis was based on 641 valid responses. Among them, 508 had no experience with palliative sedation, while only 133 had such experience. Around 92.5% of hospice nurses with experience in palliative sedation agreed with the physician's instructions to begin palliative sedation. Nurses were present at the start of sedation in nearly all cases (97.0%), and most doctors (79.7%) and family members (82.0%) were also present. However, 8.3% of them perceived that there was no difference between palliative sedation and euthanasia. Furthermore, 13.5% of participants believed that the purpose of palliative sedation was to hasten death. Conclusions: Hospice nurses play a crucial role in the process of palliative sedation, yet they also face significant challenges. It suggests that there is an urgent need in China for the development of consensus or guidelines for palliative sedation to clarify the roles of team members, including hospice nurses.

2.
Inorg Chem ; 63(24): 11113-11124, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38837698

RESUMEN

p-Benzoquinones are important organic intermediates in the synthesis of biopharmaceuticals and fine chemicals. In this study, two crystalline 3D polyoxovanadate-based metal-organic frameworks, H[Cu(tpi)2]{Cu2V7O21}·H2O (1, tpi = C18N5H13) and [Co(Htpi)2]{V4O12} (2, Htpi = C18N5H14), were synthesized, which as heterogeneous catalysts showed excellent catalytic activities for the synthesis of p-benzoquinones. Both compounds were characterized by IR, UV-vis diffuse reflectance spectroscopy, TG, XPS, X-ray diffraction, etc. In 1, {Cu2V7} clusters are connected together by copper cations and 1D Cu-organic coordination chains to yield a 3D polyoxometalate-based metal-organic framework (POMOF); in 2, adjacent 2D bimetallic oxide layers, constructed from 1D polyoxovanadate chains and cobalt ions, are further connected by 1D Co-organic coordination chains to form a 3D POMOF. Noteworthily, in the synthesis of trimethyl-p-benzoquinone, the key intermediate of vitamin E, using 2,3,6-trimethylphenol as the model substrate, the turnover frequency values for compounds 1 and 2 can, respectively, reach 607 and 380 h-1 in 8 min. Furthermore, both compounds demonstrated excellent recyclability and structural stability, characterized by PXRD and IR. The catalytic mechanism reveals that both the homolytic radical mechanism and heterolytic oxygen atom transfer mechanism are involved.

3.
BMJ Open ; 14(5): e087062, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806427

RESUMEN

INTRODUCTION: Radical mastoidectomy is a common procedure for chronic suppurative otitis media, typically performed under a microscope. The smooth operation is closely related to the clarity of the operative field. Our trial is designed to investigate whether the intravenous administration of tranexamic acid (TXA) can improve the clarity of the operative field, reduce the operative time, and increase surgeon satisfaction. METHODS AND ANALYSIS: This study is a prospective, randomised, double-blinded, controlled trial that aims to investigate the effects of TXA on patients with otitis media. The trial will include patients between the ages of 18 and 65 who will be randomly assigned to either the TXA group or the control group. In the TXA group, patients will receive 1 g of TXA diluted to 20 mL of normal saline before anaesthesia induction while the control group will receive 20 mL of normal saline. The primary outcome measure will be the Modena Bleeding Score, which will assess the clarity of the surgical field. Secondary outcomes will include the surgeon's satisfaction with surgical conditions, operation time, laboratory measurements (prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer) and levels of inflammatory factors (such as IL-6) at 24 hours postoperatively. In addition, the incidence of general adverse reactions such as postoperative nausea, vomiting and dizziness; serious adverse events such as arterial and venous thromboembolism, myocardial infarction and epilepsy within 90 days will be compared between the two groups. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee of Peking University People's Hospital (2021PHB173-001), on 19 July 2021. The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100049183.


Asunto(s)
Administración Intravenosa , Antifibrinolíticos , Mastoidectomía , Ácido Tranexámico , Humanos , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/efectos adversos , Método Doble Ciego , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/uso terapéutico , Estudios Prospectivos , Adulto , Mastoidectomía/métodos , Persona de Mediana Edad , Femenino , Masculino , Adolescente , Otitis Media Supurativa/cirugía , Otitis Media Supurativa/tratamiento farmacológico , Adulto Joven , Ensayos Clínicos Controlados Aleatorios como Asunto , Tempo Operativo , Anciano
4.
Small ; : e2311505, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38433398

RESUMEN

The rational design of heterogeneous catalysts is crucial for achieving optimal physicochemical properties and high electrochemical activity. However, the development of new amorphous-crystalline heterostructures is significantly more challenging than that of the existing crystalline-crystalline heterostructures. To overcome these issues, a coordination-assisted strategy that can help fabricate an amorphous NiO/crystalline NiCeOx (a-NiO/c-NiCeOx ) heterostructure is reported herein. The coordination geometry of the organic ligands plays a pivotal role in permitting the formation of coordination polymers with high Ni contents. This consequently provides an opportunity for enabling the supersaturation of Ni in the NiCeOx structure during annealing, leading to the endogenous spillover of Ni from the depths of NiCeOx to its surface. The resulting heterostructure, featuring strongly coupled amorphous NiO and crystalline NiCeOx , exhibits harmonious interactions in addition to low overpotentials and high catalytic stability in the oxygen evolution reaction (OER). Theoretical calculations prove that the amorphous-crystalline interfaces facilitate charge transfer, which plays a critical role in regulating the local electron density of the Ni sites, thereby promoting the adsorption of oxygen-based intermediates on the Ni sites and lowering the dissociation-related energy barriers. Overall, this study underscores the potential of coordinating different metal ions at the molecular level to advance amorphous-crystalline heterostructure design.

5.
Small ; 20(4): e2305251, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37718454

RESUMEN

Alternating current electroluminescence (ACEL) devices are attractive candidates in cost-effective lighting, sensing, and flexible displays due to their uniform luminescence, stable performance, and outstanding deformability. However, ACEL devices have suffered from limited options for the light-emitting layer, which presents a significant constraint in the progress of utilizing ACEL. Herein, a new class of ACEL phosphors based on lanthanide metal-organic frameworks (Ln-MOFs) is devised. A synthesis of lanthanide-benzenetricarboxylate (Ln-BTC) thin film on a brass grid substrate seeded with ZnO nanowires (NWs) as anchors is developed. The as-synthesized Ln-BTC thin film is employed as the emissive layer and shows visible electroluminescence driven by alternating current (2.9 V µm-1 , 1 kHz) for the first time. Mechanistic investigations reveal that the Ln-based ACEL stems from impact excitation by accelerated electrons from ZnO NWs. Fine-tuning of the ACEL color is also demonstrated by controlling the Ln-MOF compositions and introducing an extra ZnS emitting layer. The advances in these optical materials expand the application of ACEL devices in anti-counterfeiting.

6.
Altern Ther Health Med ; 29(8): 466-473, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37652418

RESUMEN

Objective: In patients with postoperative circulatory instability, the exploration of invasive arterial blood pressure (IABP) monitoring is of great significance because it can provide real-time cardiovascular function information and help medical staff to better assess and manage the patient's circulatory status. To explore the value of IABP monitoring for patients with postoperative circulatory instability in the postanesthesia care unit (PACU). Methods: From January to December 2021, 160 postoperative patients with circulatory instability were randomly divided into a control group and a study group (80 patients in each group). A random number sequence is generated through a random number table, and random numbers are distributed to different patients to achieve random grouping. SPSS was used for data processing and statistical analysis, t test was used for continuous variables, chi-square test was used for count data, and the significance level was P < .05.We compared various parameters, such as systolic blood pressure (SBP), PACU observation time, arterial partial pressure of oxygen (PaO2), total hospitalization time, heart rate (HR), arterial partial pressure of carbon dioxide (PaCO2), re-intubation rate, mean arterial pressure (MAP), adverse events, and blood oxygen saturation (SaO2), between the two groups. Flow cytometry was used to analyze changes in immune lymphocyte subsets in the patient's peripheral blood. Results: During the postoperative observation period, there were no significant differences in SBP, PaCO2, HR, SaO2, MAP, and PaO2 between the two groups (P > .05)The study group showed higher SBP, SaO2, MAP, and PaO2, and lower HR and PaCO2 compared to the control group (P < .05). The study group also had shorter PACU observation time, total hospitalization time, and a lower re-intubation rate compared to the control group (P < .05). There was no significant difference in the overall incidence of adverse events between the two groups (7.50% vs 3.75%) (P > .05). The study group showed significantly higher proportions of lymphocytes, CD3+ T cells, CD3+ CD4+ T cells, and CD3+ CD4+/CD3+ CD8+ ratio compared to the control group (P < .05). This change may reflect the patients with a positive response of the immune system, help to resist disease progress and infection. Conclusion: IABP monitoring can continuously, dynamically and accurately collect arterial blood pressure data of patients with postoperative circulatory instability, contributing to the recovery of immune competence in patients to help formulate the best clinical treatment and intervention plan. The dynamic and accurate arterial blood pressure data collection provided by IABP monitoring contributes not only to immune competence recovery but also to overall patient management and treatment planning.


Asunto(s)
Presión Arterial , Oxígeno , Humanos , Presión Sanguínea , Frecuencia Cardíaca
7.
World J Gastrointest Surg ; 15(7): 1474-1484, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37555116

RESUMEN

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

8.
Inorg Chem ; 62(26): 10120-10130, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37347205

RESUMEN

Sulfide-sulfoxide aerobic photo-oxidation is of great interest in organic and medicinal chemistry; however, developing efficient and facile heterogeneous photocatalytic systems without additional additives remains challenging. Herein, we intentionally designed and synthesized two polyoxometalate (POM)-based metalloviologen frameworks, formulated as [MII(4-PBPY)2(H2O)][MII(H2O)4][CoIII2MoVI10H4O38]·nH2O (M = Cu, n = 10 for 1; M = Co, n = 11 for 2), prepared by the mild one-step synthesis strategy and characterized in detail. X-ray single-crystal diffraction analysis shows that they present a two-dimensional layered structure formed by two parallel metalloviologen layers pillared by dimeric Evans-Showell-type POMs. The connection of POM to the metalloviologen framework enables easier flow of electrons to the POM port, which can theoretically further induce O2 to generate reactive oxygen species (O2•-) to oxidize substrates to form target products. As expected, both 1 and 2 exhibit outstanding photocatalytic activity in the oxidation of sulfides. Within 6 h, methyl phenyl sulfide can be quantitatively converted into methyl phenyl sulfoxide. The in-depth mechanism reveals that there is also a synergistic energy-transfer pathway in the catalytic system in addition to the electron-transfer pathway. In addition, the corresponding catalytic activity and structure can be well maintained after at least 10 cycle experiments.

9.
Environ Sci Pollut Res Int ; 30(35): 84595-84608, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37368210

RESUMEN

China's goal of ecological civilization construction simultaneously faces the dual strategic tasks of pollution control and carbon reduction (PCCR). In addition to carbon reduction, does the low-carbon city pilot (LCCP) further contribute to the blue sky defense? This study investigates the impact of the LCCP on air pollution by employing a multiperiod difference-in-differences (DID) model based on data from 276 Chinese cities. The results show the following: (1) Compared with nonpilot areas, the LCCP reduces PM2.5 levels in pilot areas by approximately 1.50% on average, which is achieved by "industrial restructuring", "government investment in science and technology (S&T)", and "green lifestyle". (2) The LCCP has heterogeneous effects on air quality across cities with different resource endowments and industrial attributes, showing a greater air quality improvement in nonresource-based cities (NREB cities) and old industrial base cities (OIB cities) than in other city types. (3) The positive impact of the LCCP on air improvement in the pilot areas is derived from "pollution control effects" rather than "pollution transfer effects". This study provides useful policy implications for the comprehensive green transition and exploration of synergistic governance for PCCR in China.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Ciudades , Material Particulado/análisis , Contaminación del Aire/análisis , China , Carbono , Desarrollo Económico
10.
Eur J Anaesthesiol ; 40(8): 552-559, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37218631

RESUMEN

BACKGROUND: Perioperative use of opioids has revealed significant adverse effects associated with poor postoperative outcomes. OBJECTIVE: To determine whether opioid-free anaesthesia based on thoracic paravertebral block (TPVB) could improve postoperative recovery after breast cancer surgery. DESIGN: A randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Eighty adult women undergoing breast cancer surgery were enrolled. Key exclusion criteria included remote metastasis (but not to axillary lymph nodes of the surgical side), contraindication to interventions or drugs and a history of chronic pain or chronic opioid use. INTERVENTIONS: Eligible patients were randomised at a 1 : 1 ratio to receive either TPVB-based opioid-free anaesthesia (OFA group) or opioid-based anaesthesia (control group). MAIN OUTCOME MEASURES: The primary outcome was the global score of the 15-item Quality of Recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included postoperative pain and health-related quality of life. RESULTS: The QoR-15 global score was 140.3 ±â€Š5.2 in the OFA group and 132.0 ±â€Š12.0 in the control group ( P  < 0.001). The percentage of patients with good recovery (QoR-15 global score ≥118) was 100% (40/40) in the OFA group and 82.5% (33/40) in the control group ( P  = 0.012). Improved QoR in the OFA group was also evident in sensitivity analysis that rated QoR as excellent for a score of 136 to 150, as good at 122 to 135, as moderate at 90 to 121 and as poor at 0 to 89. The OFA group had higher scores in the domains of physical comfort (45.7 ±â€Š3.0 versus 41.8 ±â€Š5.7, P  < 0.001) and physical independence (18.3 ±â€Š2.2 versus 16.3 ±â€Š4.5, P  = 0.014). The two groups did not differ in pain outcomes or health-related quality of life. CONCLUSION: TPVB-based opioid-free anaesthesia improved early postoperative quality of recovery without compromising pain control in patients undergoing breast cancer surgery. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT04390698.


Asunto(s)
Neoplasias de la Mama , Bloqueo Nervioso , Adulto , Humanos , Femenino , Neoplasias de la Mama/cirugía , Analgésicos Opioides , Calidad de Vida , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología
11.
Phytother Res ; 37(9): 4117-4132, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37246830

RESUMEN

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Transducción de Señal , Flavonoides/farmacología , Proliferación Celular , Quinasas Asociadas a rho
12.
Front Pharmacol ; 14: 1126174, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37089946

RESUMEN

Objective: The optimal dose of epidural morphine after cesarean section (CS) still remains unknown when combined with low-concentration ropivacaine based on a continuous basal infusion (CBI) mode. The aim of this study was to assess the impact of different dose of epidural morphine plus ropivacaine on maternal outcomes. Materials and methods: Data of parturients who received epidural analgesia for CS at a teaching hospital from March 2021 to June 2022 were retrospectively collected. Parturients were divided into two groups (RM3 group and RM6 group) according to different medication regimens of morphine. The implementation of epidural analgesia was performed with 3 mg morphine in RM3 group and 6 mg morphine in RM6 group in combination with 0.1% ropivacaine via a CBI pump. The primary outcomes included pain intensity at rest and movement and the incidence of urinary retention and pruritus within postoperative 48 h. The secondary outcomes included the incidence and severity of postoperative nausea and vomiting (PONV) and pruritus, the rate of rescue analgesia and grading of motor Block. Results: Totally, 531 parturients were eligible for the final analysis, with 428 and 103 parturients in the RM3 group and RM6 group, respectively. There were no statistically significant differences in the visual analogue scores (VAS) at rest and movement within postoperative 48 h between the two groups (all p > 0.05). Compared with the RM6 group, the incidence of urinary retention was lower in the RM3 group within 48 h after CS (4.0% vs. 8.7%, p = 0.044). No significant difference was found in the incidence and severity of PONV and pruritus, the rate of rescue analgesia and grading of motor block between RM3 and RM6 groups. Conclusion: Epidural 3 mg morphine plus 0.1% ropivacaine in a CBI mode can provide equal efficacy and have lower incidence of urinary retention compared with 6 mg morphine after CS.

13.
Angew Chem Int Ed Engl ; 62(26): e202303791, 2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37102633

RESUMEN

Chemically recyclable, circular polymers continue to attract increasing attention, but rendering both catalysts for depolymerization and high-performance polymers recyclable is a more sustainable yet challenging goal. Here we introduce a dual catalyst/polymer recycling system in that recyclable inorganic phosphomolybdic acid catalyzes selective depolymerization of high-ceiling-temperature biodegradable poly(δ-valerolactone) in bulk phase, which, upon reaching suitable molecular weight, exhibits outstanding mechanical performance with a high tensile strength of ≈66.6 MPa, fracture strain of ≈904 %, and toughness of ≈308 MJ m-3 , and thus markedly outperforms commodity polyolefins, recovering its monomer in pure state and quantitative yield at only 100 °C. In sharp contrast, the uncatalyzed depolymerization not only requires a high temperature of >310 °C but is also low yielding and non-selective. Importantly, the recovered monomer can be repolymerized as is to reproduce the same polymer, thereby closing the circular loop, and the recycled catalyst can be reused repeatedly for depolymerization runs without loss of its catalytic activity and efficiency.


Asunto(s)
Poliésteres , Polímeros , Poliésteres/química , Polímeros/química , Polienos , Catálisis
14.
Sci Rep ; 13(1): 5320, 2023 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-37002291

RESUMEN

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico por imagen , Retinopatía Diabética/diagnóstico por imagen , Estudios Transversales , Vasos Retinianos , Angiografía con Fluoresceína/métodos , Inflamación , Tomografía de Coherencia Óptica/métodos , Coroides/irrigación sanguínea
15.
Oncol Lett ; 25(1): 31, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36589663

RESUMEN

Numerous studies have shown that the release of stress hormones resulting from repeated exposure to chronic psychological stress increases DNA damage and promotes tumorigenesis. However, the mechanisms that enable cancerous cells adapt to stress hormone-induced DNA damage and survive remain unclear. The present study aimed to investigate the impact of stress hormones on the survival of liver cancer cells and the underlying mechanism. HepG2 human liver cancer cells were treated with dexamethasone (DEX), epinephrine (EPI) and norepinephrine (NE) and subjected to the testing of DNA damage, cell survival and cell apoptosis by alkaline comet assay, CCK-8 viability assay and flow cytometry, respectively. The protein expression levels of DNA damage response factors were determined by western blotting analysis. The results revealed that treatment of HepG2 cells with DEX, EPI and NE induced DNA damage without affecting cell survival or inducing apoptosis. The protein levels of wild-type p53-induced phosphatase 1 (Wip1), a type 2C family serine/threonine phosphatase, were increased, and the dephosphorylation of DNA damage response factors, including phosphorylated (p-)ataxia-telangiectasia mutated and p-checkpoint kinase 2, occurred following treatment with DEX, EPI and NE. In addition, a cycloheximide chase assay was performed to explore the protein stability under treatment with stress hormones. Compared with vehicle-treated cells, Wip1 exhibited increased protein stability in stress hormone-treated HepG2 cells. Eventually, the depletion of Wip1 using small interfering RNA verified the role of Wip1 in the modulation of stress hormone-induced DNA damage. These findings suggest that cancerous cells likely adapt to stress hormone-induced DNA damage via Wip1 upregulation. The present study provides an insight into the underlying mechanism that links chronic psychological stress with tumor growth and progression.

16.
J Ethnopharmacol ; 301: 115825, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36240978

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Biejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. AIM OF THE STUDY: This study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRß) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. MATERIALS AND METHODS: C57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRß signaling in CAFs and the underlying mechanism were demonstrated. RESULTS: BJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRß, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRß were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3ß) by suppressing PDGFRß expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRß, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRß activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRß signaling. CONCLUSION: BJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRß signaling.


Asunto(s)
Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Becaplermina , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones Endogámicos C57BL , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal/fisiología
17.
Front Oncol ; 13: 1305329, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38205136

RESUMEN

Background: Postoperative complications have an influence on postoperative rehabilitation, length of hospital stay and hospitalization expenses in elderly patients, especially those with higher Clavien-Dindo (C-D) classification. Patients with cancers often experience more serious postoperative complications after surgery. Different anesthesia methods can affect the postoperative outcomes of cancer patients. Regional block techniques have been recommended in guidelines for enhanced recovery after surgery. However, the relationship between regional blocks and high-grade postoperative complications remains unclear, thus, the study explored the relationship between regional block techniques and high-grade postoperative complications graded by C-D classification in elderly patients with thoracic and abdominal cancer. Method: Retrospective enrollment of eligible elderly patients admitted to Peking University People's Hospital between January 2018 and March 2022 was conducted. Propensity score matching (PSM) and univariate and multivariate regression analyses were used to analyze the potential benefits of regional blocks for elderly patients in real world practice. Results: A total of 2769 patients were enrolled in this study, including 568 who underwent colorectal resection, 2201 who underwent video-assisted thoracoscopic pneumonectomy. Among them, 2033 patients received regional block, while 736 patients did not. Statistical analysis indicated that regional blocks could reduce the incidence of postoperative complications of C-D classification Grade II or higher, with an Odds ratio (OR) of 0.742, 95% Confidence interval (CI) (0.552 to 0.996) (P = 0.047). Conclusion: Regional block is associated with a reduction in the occurrence of postoperative complications graded by C-D classification in elderly patients with thoracic and abdominal cancer. The application of regional blocks can lower the risk of high-risk complications and mortality.

19.
J Orthop Surg Res ; 17(1): 557, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36544170

RESUMEN

BACKGROUND: Osteosarcoma is highly malignant. The migration, invasion, and chemoresistance contribute to poor prognosis of osteosarcoma. Research reported that endogenous bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) promotes the progression of osteosarcoma. METHODS: In this study, the expression of EBLN3P in osteosarcoma tissue with different methotrexate (MTX) treatment responses was measured. Osteosarcoma cell lines with MTX resistance were constructed, and bioinformatic analysis was performed to explore the potential involved targets and pathways. RESULTS: Higher EBLN3P was associated with MTX resistance. Downregulation of LncEBLN3P decreased the MTX resistance of osteosarcoma cells by sponging miR-200a-3p, an important microRNA that affects epithelial-mesenchymal transition (EMT). The decreased miR-200a-3p resulted in the upregulation of its target gene O-GlcNAc transferase (OGT), which in turn promoted the EMT process of osteosarcoma cells. Further analysis confirmed that the loss of OGT and over-expression of miR-200a-3p could partly abolish the MTX resistance induced by LncEBLN3P. CONCLUSION: LncEBLN3P is upregulated in osteosarcoma and increases the MTX resistance in osteosarcoma cells through downregulating miR-200a-3p, which in turn promoted the EMT process of osteosarcoma cells by increasing the OGT.


Asunto(s)
Neoplasias Óseas , Resistencia a Antineoplásicos , Metotrexato , MicroARNs , Osteosarcoma , ARN Largo no Codificante , Humanos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Metotrexato/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Osteosarcoma/patología , Seudogenes , ARN Largo no Codificante/genética , Resistencia a Antineoplásicos/genética
20.
Nucleic Acids Res ; 50(20): e119, 2022 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-36099417

RESUMEN

Paraspeckles are ribonucleoprotein granules assembled by NEAT1_2 lncRNA, an isoform of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1). Dysregulation of NEAT1_2/paraspeckles has been linked to multiple human diseases making them an attractive drug target. However currently NEAT1_2/paraspeckle-focused translational research and drug discovery are hindered by a limited toolkit. To fill this gap, we developed and validated a set of tools for the identification of NEAT1_2 binders and modulators comprised of biochemical and cell-based assays. The NEAT1_2 triple helix stability element was utilized as the target in the biochemical assays, and the cellular assay ('ParaQuant') was based on high-content imaging of NEAT1_2 in fixed cells. As a proof of principle, these assays were used to screen a 1,200-compound FDA-approved drug library and a 170-compound kinase inhibitor library and to confirm the screening hits. The assays are simple to establish, use only commercially-available reagents and are scalable for higher throughput. In particular, ParaQuant is a cost-efficient assay suitable for any cells growing in adherent culture and amenable to multiplexing. Using ParaQuant, we identified dual PI3K/mTOR inhibitors as potent negative modulators of paraspeckles. The tools we describe herein should boost paraspeckle studies and help guide the search, validation and optimization of NEAT1_2/paraspeckle-targeted small molecules.


Asunto(s)
Núcleo Celular , Paraspeckles , ARN Largo no Codificante , Humanos , Núcleo Celular/genética , Paraspeckles/efectos de los fármacos , Paraspeckles/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/química , Inhibidores de Proteínas Quinasas/farmacología , Descubrimiento de Drogas
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