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1.
PLoS One ; 19(3): e0297791, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38536845

RESUMO

This cross-sectional study investigated the effects of value-based leadership and growth mindset on the intrinsic work motivation of Chinese lecturers. In addition, this study used age as a categorical moderator to investigate generational differences between the effects of Millennials and their predecessors. A sample of 518 lecturers from various Chinese universities was used to collect data, and SEM-PLS was used to analyse the data. The results showed that value-based leadership and growth mindset had a significant positive impact on both younger and older lecturers' intrinsic work motivation, with the effect of value-based leadership on younger lecturers' intrinsic motivation being significantly stronger than on older lecturers' intrinsic motivation, whereas the effect of growth mindset on intrinsic work motivation did not differ significantly between the younger and older groups. This study contributes to the existing research literature by contrasting the value-based leadership and growth mindset in relation to lecturers' intrinsic work motivation across younger and older groups in Chinese higher education settings, where greater heterogeneity between age groups was identified. The findings also provided university administrators with recommendations for boosting the intrinsic work motivation of lecturers, influencing future education policy.


Assuntos
Liderança , Motivação , Humanos , Estudos Transversais
2.
APMIS ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466886

RESUMO

In brain metastases, radiation necrosis (RN) is a complication that arises after single or multiple fractionated stereotactic radiosurgery (SRS/FSRS), which is challenging to distinguish from local recurrence (LR). Studies have shown increased RN incidence rates in non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations (ODMs) or receiving tyrosine kinase inhibitors (TKIs). This study investigated enlarging brain lesions following SRS/FSRS, for which additional surgeries were performed to distinguish between RN and LR. We investigated seven NSCLC patients with ODMs undergoing SRS/FSRS for BM and undergoing surgery for suspicion of LR on MRI imaging. Descriptive statistics were performed. Among the seven patients, six were EGFR+, while one was ALK+. The median irradiation dose was 30 Gy (range, 20-35 Gy). The median time to develop RN after SRS/FSRS was 11.1 months (range: 6.3-31.2 months). Moreover, gradually enlarging lesions were found in all patients after 6 months post-SRS/FSR. Brain radiation necrosis was pathologically confirmed in all the patients. RN should be suspected in NSCLC patients when lesions keep enlarging after 6 months post-SRS/FSRS, especially for patients with ODMs and receiving TKIs. Further, this case series indicates that further dose reduction might be necessary to avoid RN for such patients.

3.
Heliyon ; 10(4): e26607, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404889

RESUMO

This study presents a comprehensive bibliometric analysis of the literature on psychological capital (PsyCap) within higher education institutions (HEIs). Its main objective is to offer an encompassing perspective on this field's current state and potential developments. To achieve this, the study examines present research trends and predicts future directions using a bibliometric approach. A total of 412 journal articles were gathered from the Web of Science database. The analysis identifies influential publications, outlines the knowledge structure, and forecasts future trends through bibliographic coupling and co-word analyses. The bibliographic coupling revealed five distinct clusters, while the co-word analysis identified four clusters. Despite the growing significance of PsyCap research in HEIs, there remains a need for greater academic efforts to comprehend the research landscape fully. This paper provides valuable insights into the expanding area of PsyCap research within HEIs. In conclusion, the study sheds light on the extensive research conducted on PsyCap in the context of HEIs and offers insights into its potential for further growth.

4.
FEBS J ; 291(8): 1795-1812, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308810

RESUMO

Ataxin-2 (Atx2) is a polyglutamine (polyQ) protein, in which abnormal expansion of the polyQ tract can trigger protein aggregation and consequently cause spinocerebellar ataxia type 2 (SCA2), but the mechanism underlying how Atx2 aggregation leads to proteinopathy remains elusive. Here, we investigate the molecular mechanism and cellular consequences of Atx2 aggregation by molecular cell biology approaches. We have revealed that either normal or polyQ-expanded Atx2 can sequester Raptor, a component of mammalian target of rapamycin complex 1 (mTORC1), into aggregates based on their specific interaction. Further research indicates that the polyQ tract and the N-terminal region (residues 1-784) of Atx2 are responsible for the specific sequestration. Moreover, this sequestration leads to suppression of the mTORC1 activity as represented by down-regulation of phosphorylated P70S6K, which can be reversed by overexpression of Raptor. As mTORC1 is a key regulator of autophagy, Atx2 aggregation and sequestration also induces autophagy by upregulating LC3-II and reducing phosphorylated ULK1 levels. This study proposes that Atx2 sequesters Raptor into aggregates, thereby impairing cellular mTORC1 signaling and inducing autophagy, and will be beneficial for a better understanding of the pathogenesis of SCA2 and other polyQ diseases.


Assuntos
Ataxina-2 , Ataxina-2/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo
5.
Heliyon ; 10(3): e24783, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314294

RESUMO

This study utilizes bibliometric analysis to examine historical and present research patterns in the area of energy transition and green finance and to forecast potential future domains. Using the bibliometric method, 328 scholarly articles from the Web of Science database were evaluated. This paper identifies influential publications, maps the research landscape, and forecasts emerging tendencies through co-citation and co-word analyses. Co-citation analysis found three main clusters, while co-word analysis revealed four main clusters. Despite the growing significance of research on energy transition and green finance research, further in-depth investigation is necessary to offer a thorough depiction of the research domain. This research represents a pioneering endeavour in the utilization of bibliometric analysis to investigate the interrelationship between two items. It offers valuable insights into the rapidly expanding field of energy transition and green finance, effectively highlighting its contours and indicating potential future developments.

6.
Heliyon ; 10(4): e26472, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420486

RESUMO

This study provides a bibliometric analysis of smart hotel research, drawing from 613 publications in the Web of Science (WoS) database to examine scholarly trends and developments in this dynamic field. Smart hotels, characterized by integrating advanced technologies such as AI, IoT, cloud computing, and big data, aim to redefine customer experiences and operational efficiency. Utilizing co-citation and co-word analysis techniques, the research delves into the depth of literature from past to future trends. In co-citation analysis, clusters including "Sustainable Hotel and Green Hotel", "Theories Integration in Smart Hotel Research", and "Consumers' Decisions about Green Hotels" underscore the pivotal areas of past and current research. Co-word analysis further reveals emergent trend clusters: "The New Era of Sustainable Tourism", "Elevating Standards and Guest Loyalty", and "Hotels' New Sustainable Blueprint in Modern Travel". These clusters reflect the industry's evolving focus on sustainability and technology-enhanced guest experiences. Theoretically, this research bridges gaps in smart hotel literature, proposing new frameworks for understanding customer decisions amid technological advancements and environmental responsibilities. Practically, it offers valuable insights for hotel managers, guiding technology integration strategies for enhanced efficiency and customer loyalty while underscoring the critical role of green strategies and sustainability.

7.
Heliyon ; 10(4): e26241, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390183

RESUMO

This comprehensive bibliometric study analyzes 1820 journal articles from the Web of Science database to explore Equity, Diversity, and Inclusion (EDI) leadership in higher education institutions (HEIs). Utilizing co-citation and co-word analysis, the study identifies distinct thematic clusters. The co-citation analysis reveals five key themes: Race, Diversity, and Inclusion (RDI), Diversity, Leadership, and Self-Efficacy (DLSE), Gender Dynamics and Leadership Challenges, Women's Representation in Academic Medicine Leadership, and Transformational Leadership in HEIs. Meanwhile, the co-word analysis highlights three critical areas: Transformative Collaborative Resilience in HEIs, Advancing Gender Equality in Academic Medicine and STEM, and Inclusive Educational Leadership in HEIs. These themes collectively provide a deep understanding of the EDI leadership field's intellectual structure, suggesting significant areas for future research and practical application. The study emphasizes the necessity for HEIs to engage comprehensively in EDI leadership research, shedding light on the importance of transformative collaborative resilience, gender equality in STEM, and inclusive leadership. This research offers valuable insights for developing effective EDI leadership policies and practices, highlighting the interconnectedness of these themes in fostering a more equitable, diverse, and inclusive environment in higher education and beyond.

8.
Int Immunopharmacol ; 128: 111527, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38215655

RESUMO

To predict early remission following anti-integrin therapy (vedolizumab [VDZ]) in patients with moderate-to-severe active ulcerative colitis (UC) using non-invasive biomarkers. The clinical data of a cohort of 33 patients with moderate-to-severe active UC admitted to the Department of Gastroenterology at Suzhou Municipal Hospital between January 2021 and December 2022 were collected. Of these, 9 patients declined VDZ treatment, and 21 received VDZ at doses of 300 mg weeks 0, 2, and 6, each administered within a 30-minute infusion period. The treatment regimen aimed to induce remission of clinical symptoms; hence, the same dose was administered every 8 weeks. At weeks 0 and 14, serum C-reactive protein (CRP) and erythrocyte sedimentation rate were measured using a modified Mayo score. In addition to clinical assessment, stool samples at baseline and weeks 14 were collected and evaluated using 16SrRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS). Clinical remission was determined based on the clinical symptoms and partial Mayo scores. In patients who received VDZ, the strains of bifidobacterium longum (P = 0.022) and bacteroides sartorii (P = 0.039) significantly increased after treatment than before treatment. GC-MS analysis showed that taurine (P = 0.047) and putrescine (P = 0.035) significantly decreased after treatment. Furthermore, while acetamide exhibited a notable increase (P = 0.001), arachidic acid (P < 0.001) and behenic acid (P = 0.005) demonstrated statistically significant elevations. The combined prediction model of acetamide, taurine, and putrescine demonstrated a high predictive value of early remission in patients with moderate-to-severe active UC following VDZ treatment (area under the curve = 0.911, P = 0.014).


Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Putrescina/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Resultado do Tratamento , Indução de Remissão , Acetamidas , Taurina , Estudos Retrospectivos
9.
PLoS One ; 18(12): e0294658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38117775

RESUMO

The first year of university is one of the most difficult times in a student's life due to numerous changes that occur. This cross-sectional study explores the concept of parental and peer attachment, which has been researched for its ability to predict students' success in higher education. Yet, less research has investigated the mechanisms underpinning the relationship between attachment and university adjustment among first-year students. Hence, the aim of this study was to examine the impact of parent and peer attachment on first-year university students, and understand how these attachments can facilitate university adjustment through identity exploration. This investigation is underpinned by Bowlby and Ainsworth's attachment theory and Arnett's emerging adulthood theory. Data were collected from 568 first-year students at a public university in Sabah, Malaysia, via adapted questionnaires. Structural equation modelling was employed using SmartPLS Software 3.0 to analyse the data. The study found that identity exploration mediates the relationship between parental trust, peer communication, and university adjustment. The findings of this study provide valuable insights for professionals working with emerging adult clients, especially those in higher education institutions, aiming to enhance the adjustment level among first-year students.


Assuntos
Amigos , Estudantes , Adulto , Humanos , Universidades , Estudos Transversais , Pais
10.
Eur J Med Chem ; 260: 115763, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659196

RESUMO

ProTide prodrug technology has emerged as a promising way for the development of anti-viral and anti-tumor drugs, whereas, there are fewer applications for the treatment of liver cancer. Herein, a series of distinct 3'-ester ProTide prodrugs of 5-fluoro-2'-deoxyuridine (FdUR) were synthesized and evaluated for their anti-liver cancer activity. The most efficient prodrug 11b reached a sub-micromolar activity (IC50 = 0.42 ± 0.13 µM) against HepG2 and over 100-fold and 200-fold improvements compared to 5-FU, respectively. 11b also demonstrated favorable selectivity towards normal liver cells L-02 (IC50 > 100 µM). In vitro metabolic stability studies revealed that 11b is stable in the plasma and could be activated rapidly in the liver, which supported that 11b is liver-targeted. Importantly, to more accurately evaluate the anti-HCC activity of 11b, the liver orthotopic model was built and 11b significantly suppressed tumor growth (TGI = 75.5%) at a dose of 60 mg/kg/2d in vivo without obvious toxicity. Overall, these promising results indicated that 11b could serve as a safe and effective prodrug of 5-FU nucleoside for liver cancer therapy.


Assuntos
Neoplasias Hepáticas , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Desoxiuridina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico
11.
Int Immunopharmacol ; 124(Pt B): 110955, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37725845

RESUMO

BACKGROUND: The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. METHODS: Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. RESULTS: A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. CONCLUSION: Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer.


Assuntos
Neoplasias Esofágicas , Recidiva Local de Neoplasia , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias Esofágicas/terapia , Intervalo Livre de Progressão
12.
J Environ Manage ; 345: 118819, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37597367

RESUMO

The use of seawater as a substitute for pure water as supplemental moisture raises questions about its effect on the physicochemical properties of hydrochar. Therefore, this study aimed to investigate the feasibility of using seawater as supplemental moisture by comparing the physicochemical properties of products obtained through Co-hydrothermal carbonization of chicken manure and cornstalk under seawater and deionized water conditions. By varying the HTC temperature and blending ratios of CM and CS to investigate comprehensively the effect of seawater. Results indicated that the hydrochar yield experienced a variation from 54.54% to 57.40%, while the IC value changed from 7.69% to 8.46% as the ratio of CM:CS shifted from 3:1 to 1:3 under seawater conditions. The higher heating value of the hydrochars obtained under seawater conditions was lower than those obtained under deionized water conditions. This suggests that seawater conditions promote the hydrolysis reaction of organic solid waste. Furthermore, it was observed that when no lignin hydrolysis reaction occurred, seawater conditions had no discernible effect on the fuel quality of the hydrochar. However, at an HTC temperature of 250 °C, the fuel quality of the hydrochar obtained under seawater conditions was notably inferior to that of the hydrochar obtained under deionized water. Thus, an HTC temperature lower than 250 °C is necessary for the hydrothermal carbonization of organic solid waste under seawater conditions. Moreover, the relative content of surface -C-(C, H)/CC of the hydrochar obtained under seawater conditions was lower than that obtained under deionized water conditions, indicating that the hydrochar had a low degree of aromatization. Additionally, there was a significant increase in the immobilized Mg atoms in the hydrochar under seawater conditions, which affected the hydrochar yield and higher heating value of the hydrochar. This research presents a theoretical foundation for preparing solid fuels and materials using hydrothermal carbonization of saltwater as supplemental moisture.


Assuntos
Carbono , Esterco , Animais , Galinhas , Resíduos Sólidos , Água do Mar , Água , Temperatura
13.
Sensors (Basel) ; 23(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37447839

RESUMO

Vehicle Ad-hoc network (VANET) can provide technical support and solutions for the construction of intelligent and efficient transportation systems, and the routing protocol directly affects the efficiency of VANET. The rapid movement of nodes and uneven density distribution affect the routing stability and data transmission efficiency in VANET. To improve the local optimality and routing loops of the path-aware greedy perimeter stateless routing protocol (PA-GPSR) in urban sparse networks, a weight-based path-aware greedy perimeter stateless routing protocol (W-PAGPSR) is proposed. The protocol is divided into two stages. Firstly, in the routing establishment stage, the node distance, reliable node density, cumulative communication duration, and node movement direction are integrated to indicate the communication reliability of the node, and the next hop node is selected using the weight greedy forwarding strategy to achieve reliable transmission of data packets. Secondly, in the routing maintenance stage, based on the data packet delivery angle and reliable node density, the next hop node is selected for forwarding using the weight perimeter forwarding strategy to achieve routing repair. The simulation results show that compared to the greedy peripheral stateless routing protocol (GPSR), for the maximum distance-minimum angle greedy peripheral stateless routing (MM-GPSR) and PA-GPSR protocols, the packet loss rate of the protocol is reduced by an average of 24.47%, 25.02%, and 14.12%, respectively; the average end-to-end delay is reduced by an average of 48.34%, 79.96%, and 21.45%, respectively; and the network throughput is increased by an average of 47.68%, 58.39%, and 20.33%, respectively. This protocol improves network throughput while reducing the average end-to-end delay and packet loss rate.


Assuntos
Algoritmos , Tecnologia sem Fio , Reprodutibilidade dos Testes , Simulação por Computador , Redes de Comunicação de Computadores
14.
J Biol Chem ; 299(8): 105019, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422193

RESUMO

Poly(A)-binding protein nuclear 1 (PABPN1) is an RNA-binding protein localized in nuclear speckles, while its alanine (Ala)-expanded variants accumulate as intranuclear aggregates in oculopharyngeal muscular dystrophy. The factors that drive PABPN1 aggregation and its cellular consequences remain largely unknown. Here, we investigated the roles of Ala stretch and poly(A) RNA in the phase transition of PABPN1 using biochemical and molecular cell biology methods. We have revealed that the Ala stretch controls its mobility in nuclear speckles, and Ala expansion leads to aggregation from the dynamic speckles. Poly(A) nucleotide is essential to the early-stage condensation that thereby facilitates speckle formation and transition to solid-like aggregates. Moreover, the PABPN1 aggregates can sequester CFIm25, a component of the pre-mRNA 3'-UTR processing complex, in an mRNA-dependent manner and consequently impair the function of CFIm25 in alternative polyadenylation. In conclusion, our study elucidates a molecular mechanism underlying PABPN1 aggregation and sequestration, which will be beneficial for understanding PABPN1 proteinopathy.


Assuntos
Distrofia Muscular Oculofaríngea , Poliadenilação , Humanos , Alanina/metabolismo , Distrofia Muscular Oculofaríngea/genética , Distrofia Muscular Oculofaríngea/metabolismo , Proteína I de Ligação a Poli(A)/genética , Proteína I de Ligação a Poli(A)/metabolismo , RNA/metabolismo
15.
Front Cell Dev Biol ; 11: 1190266, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476154

RESUMO

Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal.

16.
Acta Biochim Biophys Sin (Shanghai) ; 55(5): 736-748, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37171184

RESUMO

Nine polyglutamine (polyQ) proteins have already been identified that are considered to be associated with the pathologies of neurodegenerative disorders called polyQ diseases, but whether these polyQ proteins mutually interact and synergize in proteinopathies remains to be elucidated. In this study, 4 polyQ-containing proteins, androgen receptor (AR), ataxin-7 (Atx7), huntingtin (Htt) and ataxin-3 (Atx3), are used as model molecules to investigate their heterologous coaggregation and consequent impact on cellular proteostasis. Our data indicate that the N-terminal fragment of polyQ-expanded (PQE) Atx7 or Htt can coaggregate with and sequester AR and Atx3 into insoluble aggregates or inclusions through their respective polyQ tracts. In vitro coprecipitation and NMR titration experiments suggest that this specific coaggregation depends on polyQ lengths and is probably mediated by polyQ-tract interactions. Luciferase reporter assay shows that these coaggregation and sequestration effects can deplete the cellular availability of AR and consequently impair its transactivation function. This study provides valid evidence supporting the viewpoint that coaggregation of polyQ proteins is mediated by polyQ-tract interactions and benefits our understanding of the molecular mechanism underlying the accumulation of different polyQ proteins in inclusions and their copathological causes of polyQ diseases.


Assuntos
Doenças Neurodegenerativas , Proteostase , Humanos , Peptídeos/química , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Ataxina-3/genética , Ataxina-3/metabolismo
17.
BMC Cancer ; 23(1): 318, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024843

RESUMO

BACKGROUND: Immunotherapy has made significant advances in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), but data in combination with radiotherapy are scarce. This study aims to assess the safety and efficacy of chemoimmunotherapy combined with thoracic radiotherapy in patients with ES-SCLC. METHODS: This single-center retrospective study analyzed patients with ES-SCLC who received standard platinum-etoposide chemotherapy combined with atezolizumab or durvalumab immunotherapy as induction treatment, followed by consolidative thoracic radiotherapy (CTRT) before disease progression in the first-line setting. Adverse events during radiotherapy with or without maintenance immunotherapy and survival outcomes were assessed. RESULTS: Between December 2019 and November 2021, 36 patients with ES-SCLC were identified to have received such treatment modality at one hospital. The number of metastatic sites at diagnosis was 1-4. The biological effective dose of CTRT ranged from 52 to 113 Gy. Only two patients (6%) developed grade 3 toxic effect of thrombocytopenia, but none experienced grade 4 or 5 toxicity. Four patients developed immune-related pneumonitis during the induction treatment period but successfully completed later CTRT. The rate of radiation-related pneumonitis was 8% with grades 1-2 and well tolerated. The median progression-free survival (PFS) was 12.8 months, but the median overall survival (OS) was not determined. The estimated 1-year OS was 80.2% and 1-year PFS was 53.4%. CONCLUSIONS: Immunotherapy combined with CTRT for ES-SCLC is safe and has ample survival benefit.


Assuntos
Imunoterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Etoposídeo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Platina/uso terapêutico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia
18.
Antioxidants (Basel) ; 12(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37107295

RESUMO

Aging is a complex process of impaired physiological integrity and function, and is associated with increased risk of cardiovascular disease, diabetes, neurodegeneration, and cancer. The cellular environment of the aging brain exhibits perturbed bioenergetics, impaired adaptive neuroplasticity and flexibility, abnormal neuronal network activity, dysregulated neuronal Ca2+ homeostasis, accumulation of oxidatively modified molecules and organelles, and clear signs of inflammation. These changes make the aging brain susceptible to age-related diseases, such as Alzheimer's and Parkinson's diseases. In recent years, unprecedented advances have been made in the study of aging, especially the effects of herbal/natural compounds on evolutionarily conserved genetic pathways and biological processes. Here, we provide a comprehensive review of the aging process and age-related diseases, and we discuss the molecular mechanisms underlying the therapeutic properties of herbal/natural compounds against the hallmarks of brain aging.

19.
Molecules ; 27(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36431966

RESUMO

Cervical cancer is a common gynecological malignancy afflicting women all over the world. Ginsenoside Rh2 (GRh2), especially 20(S)-GRh2, is a biologically active component in the natural plant ginseng, which can exhibit anticancer effects. Here, we aimed to investigate the effect of 20(S)-GRh2 on cervical cancer and elucidate the underlying mechanism through RNA-seq. In this study, the CCK-8 assay showed that 20(S)-GRh2 inhibited HeLa cell viability in a time- and dose-dependent manner. Caspase 3 activity and Annexin V staining results showed that 20(S)-GRh2 induced apoptosis of HeLa cells. Gene function enrichment analysis revealed that the biological process gene ontology (GO) terms were associated with the apoptotic signaling pathway. Biological process GO terms' similarity network indicated that apoptosis might be from endoplasmic reticulum stress (ERs). Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that 20(S)-GRh2 primarily modulates apoptosis pathway genes. Combined protein-protein interaction network, hub gene screening, and qPCR validation data showed that ERs-related genes (ATF4 and DDIT3) and the downstream apoptotic genes (JUN, FOS, BBC3, and PMAIP1) were potential novel targets of 20(S)-GRh2-inducing cervical cancer cell apoptosis. Differential transcript usage analysis indicated that DDIT3 is also a differential transcript and its usage of the isoform (ENST00000552740.5) was reduced by 20(S)-GRh2. Molecular docking suggested that 20(S)-GRh2 binds to the targets (ATF4, DDIT3, JUN, FOS, BBC3, and PMAIP1) with high affinity. In conclusion, our findings indicated that 20(S)-GRh2 might promote ERs-related apoptosis of cervical cancer cells by regulating the DDIT3-based targets' signal pathway. The role of 20(S)-GRh2 at the transcriptome level provides novel targets and evidence for the treatment of cervical cancer.


Assuntos
Estresse do Retículo Endoplasmático , Neoplasias do Colo do Útero , Feminino , Humanos , Células HeLa , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Simulação de Acoplamento Molecular , Apoptose , Proteínas Reguladoras de Apoptose , Expressão Gênica
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