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1.
Sci Rep ; 14(1): 17876, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090194

RESUMO

Throughout the history of coal mining in all countries of the world, large areas of goaf have been left behind, and sudden collapses and surface subsidence of large areas of goaf may occur, especially for mining areas with long mining cycles. The northern new district of the Liaoyuan mining area has been subjected to nearly half a century of mining activities, accompanied by a gradual accumulation of disasters, which have occurred frequently in recent years. In order to assess the stability of the goaf in the study area, this paper proposes a hybrid decision-making multi-factor integrated evaluation method. The distribution of underground goafs was determined using geophysical exploration techniques (seismic survey and transient electromagnetic method) and geological drilling exploration. First, an evaluation index system was established based on the specifications of the goaf, the ecological and geological environment, and the mining conditions; the system included 14 indicators. Two weight calculation methods, AHP-EWM, were employed to determine the comprehensive weight of each indicator by combining subjective and objective weights on the basis of improved game theory. Subsequently, the fuzzy comprehensive evaluation method was utilised to complete the stability rating of each block in the study area, and MapGIS and ArcGIS were employed to complete the drawing of the stability zoning map of the northern new district goaf. The study area was divided into three zones of stability, basic stability and instability, according to the critical value. These zones accounted for 23.03%, 36.45% and 40.52% of the total area of the study area, respectively. The comprehensive on-site investigation revealed a decrease in the size and number of collapse pits and the rate of damage to the houses from the unstable zone to the stable zone. This indicates that the results of the division are consistent with the actual situation. The classification results are consistent with the actual ground disaster situation, thus verifying the rationality and validity of the evaluation method. The results indicate that the stability of the study area is generally at the lower middle level.

2.
Sci Rep ; 14(1): 18709, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134588

RESUMO

In order to strengthen the overall planning and coordination of urban construction and ecological space in Baishan City, we should formulate a scientific land type planning of Production-Living-Ecological Space (PLES). In this paper, land use dynamic attitude model, land use transfer matrix, land use function center of gravity transfer model, eco-environmental quality index(EEQI) and geographic detector model are used to discuss the spatio-temporal evolution of PLES in Baishan City from 2000 to 2020. Spatio-temporal evolution of EEQI and its influencing factors. The results show that: (1) During the study period, Baishan City showed the characteristics that the production space first increased and then decreased, the ecological space decreased, and the living space continued to increase. Among them, the ecological space is the dominant space of Baishan City, covering an area of more than 80%. From the perspective of the transformation of PLES, from 2000 to 2020, Baishan City is mainly characterized by the transformation of ecological space into production space and living space. In the second type of space, green ecological space, forestry ecological space and other ecological space have decreased, while other types of space have increased in varying degrees. (2) During the study period, the overall EEQI of Baishan City remained in good condition, and the ecological environment quality(EEQ) of the three periods were 0.6571, 0.6412 and 0.6562 respectively. The higher EEQI is distributed in Changbai County and Linjiang City, while the areas with lower EEQI are concentrated in the north-central part of Hunjiang City, the middle part of Jiangyuan District and the northwest of Fusong County. (3) According to the analysis of the influencing factors of EEQ, the influence of the factors of spatial differentiation of EEQI in Baishan City changed significantly from 2000 to 2020, and the average annual rainfall was the core factor affecting the spatial differentiation of EEQ in Baishan City, the second is the urbanization rate and the distance from the county government, and the interaction between the average annual rainfall and the distance from the county government has a strong influence on the spatial differentiation of EEQ in Baishan City. This study reveals the evolution of spatial types and EEQ of PLES in Baishan City, and provides a scientific reference for the effective management and utilization of land resources in Baishan City.

3.
PLoS One ; 19(8): e0308673, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39137209

RESUMO

OBJECTIVE: Relative to explicit absenteeism, nurses' presenteeism has a more lasting impact and is more harmful and costly. This study aimed to explore the relationship between work-family conflict, perceived social support, and presenteeism and whether perceived social support mediates the relationship between work-family conflict and presenteeism among ICU nurses working on shifts in Chinese public hospitals. MATERIALS AND METHODS: A cross-sectional research design was conducted from January to April 2023 in Sichuan Province, China. A total of 609 valid questionnaires were collected. The questionnaires contained information on demographic characteristics, the Work-Family Conflict (WFC) scale, the Perceived Social Support Scale (PSSS), and Stanford Presenteeism Scale-6 (SPS-6). Multiple stratified regression was used to explore the mediating role of perceived social support between work-family conflict and presenteeism. The mediating effect of perceived social support in work-family conflict and presenteeism was tested by Model 4 in the PROCESS 4.1 macro program in SPSS. RESULTS: A total of 609 nurses were included in this study, and the mean presenteeism score for ICU nurses working on shifts was 16.01 ± 4.293 (Mean ± SD), with high presenteeism accounting for 58.46%. After controlling for sociodemographic characteristic variables, work-family conflict was positively associated with presenteeism, explaining 7.7% of the variance. High perceived social support was related to low presenteeism, explaining 11.5% of the variance. Perceived social support mediated the association between work-family conflict and presenteeism among ICU nurses working on shifts. CONCLUSIONS: Chinese shift-work ICU nurses' high presenteeism scores deserve managers' attention. Work-family conflict is a significant predictor of nurses' presenteeism. Perceived social support is essential in improving nurses' work-family conflict and mediates the relationship between work-family conflict and presenteeism. Improving social support can reduce the impact of work-family conflict on presenteeism among nurses working shifts.


Assuntos
Hospitais Públicos , Unidades de Terapia Intensiva , Presenteísmo , Apoio Social , Humanos , Feminino , Adulto , Estudos Transversais , Masculino , Presenteísmo/estatística & dados numéricos , China , Inquéritos e Questionários , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Pessoa de Meia-Idade , Enfermagem de Cuidados Críticos , Enfermeiras e Enfermeiros/psicologia , Família/psicologia
4.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2211-2222, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39044585

RESUMO

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.


Assuntos
Antineoplásicos , Doxorrubicina , Neoplasias Renais , Organoides , Humanos , Organoides/efeitos dos fármacos , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/análogos & derivados , Pelve Renal/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Receptores de Hialuronatos/metabolismo , Proliferação de Células/efeitos dos fármacos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/tratamento farmacológico
5.
Front Psychol ; 15: 1365817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952833

RESUMO

Background: Meaning in life is a crucial aspect of psychological well-being, often overlooked despite its clinical significance. This warrants further investigation, especially regarding its relationship with frailty and psychological resilience. Objective: This study aims to assess the status and relevance of frailty, psychological resilience, and meaning in life among older adults in Chinese nursing homes. Additionally, it explores the mediating role of psychological resilience between frailty and meaning in life, providing insights to improve the meaning in life for older adults in nursing homes. Methods: Between August 2022 and November 2022, 302 older adults in Chinese nursing homes were selected using convenience sampling. The study utilized the Socio-demographic Characteristics Questionnaire, Tilburg Frailty Indicator, Connor-Davidson Resilience Scale, and the Source of Meaning Scale for Older Adults. A face-to-face questionnaire survey was conducted, and SPSS 27.0 was employed for analyzing correlations between frailty, psychological resilience, and meaning in life. The mediating effect of psychological resilience was assessed using Model 4 in the Process plug-in. Results: Older adults in nursing homes exhibited a frailty total score of 4.00 (2.00, 5.00), with a prevalence of 28.5%. Psychological resilience scored 66.00 (51.75, 76.00), and meaning in life scored 149.00 (132.00, 158.25). Frailty showed a negative correlation with both meaning in life and psychological resilience, while meaning in life demonstrated a positive correlation with psychological resilience. Psychological resilience exhibited a partial mediating effect, accounting for 51.04% of the total effect between frailty and meaning in life. Conclusion: Frailty incidence is high among older adults in nursing homes, with psychological resilience at a general level and meaning in life in the upper middle level. Psychological resilience plays a crucial role as a partial mediator between frailty and meaning in life. Timely assessment of frailty, targeted interventions, and improvements in psychological resilience are essential for enhancing the meaning in life and promoting successful aging.

6.
Polymers (Basel) ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000676

RESUMO

In seasonally frozen soil areas, high-steep rocky slopes resulting from open-pit mining and slope cutting during road construction undergo slow natural restoration, making ecological restoration generally challenging. In order to improve the problems of external soil attachment and long-term vegetation growth in the ecological restoration of high-steep rocky slopes in seasonally frozen areas, this study conducted a series of experiments through the combined application of polyacrylamide (PAM) and carboxymethyl cellulose (CMC) to assess the effects of soil amendments on soil shear strength, water stability, freeze-thaw resistance, erosion resistance, and vegetation growth. This study showed that the addition of PAM-CMC significantly increased the shear resistance and cohesion of the soil, as well as improving the water stability, freeze-thaw resistance, and erosion resistance, but the internal friction angle of the soil was not significantly increased after reaching a certain content. Moderate amounts of PAM-CMC can extend the survival of vegetation, but overuse may cause soil hardening and inhibit vegetation growth by limiting air permeability. It was observed by a scanning electron microscope (SEM) that the gel membrane formed by PAM-CMC helped to "bridge" and bind the soil particles. After discussion and analysis, the optimum application rate of PAM-CMC was 3%, which not only improved the soil structure but also ensured the growth of vegetation in the later stage under the optimum application rate. Field application studies have shown that 3% PAM-CMC-amended soil stably attaches to high-steep rocky slopes, with stable vegetation growth, and continues to grow after five months of freeze-thaw action, with no need for manual maintenance after one year.

7.
Sci Total Environ ; 946: 174427, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38964413

RESUMO

Hazard assessment is fundamental in the field of disaster risk management. With the increase in global warming, compound water and temperature events have become more frequent. Current research lacks risk assessments of low temperatures and their compound events, necessitating relevant hazard assessment work to improve the accuracy and diversity of maize disaster prevention and mitigation strategies. This study comparatively analyzed the dynamic evolution characteristics and hazards of compound drought/waterlogging and low temperature events (CDLEs and CWLEs) for maize in the Songliao Plain during different growth periods from 1981 to 2020. First, composite drought/waterlogging and low temperature magnitude indices (CDLMI and CWLMI) were constructed to quantify the intensity of CDLEs and CWLEs by fitting non-exceedance probabilities. Next, static and dynamic hazard assessment models were developed by fitting probability density and cumulative probability density curves to CDLMI and CWLMI. The results showed that the correlations between SPRI and LTI across different decades were mainly negative during the three growth periods. The hazard ratings for both CDLEs and CWLEs were relatively high in the northern part of the study area, consistent with the higher occurrence, duration, and severity of both CDLEs and CWLEs at higher latitudes. Relative to 2001-2010, the center of gravity of hazard shifted southward for CDLEs and northward for CWLEs in 2011-2020. The mean duration, frequency, and hazard were generally higher for CWLEs, but CDLEs were associated with more severe maize yield reductions. This study provides new insights into compound disaster risk assessment, and the research methodology can be generalized to other agricultural growing areas to promote sustainable development of agricultural systems and food security.


Assuntos
Secas , Zea mays , Zea mays/crescimento & desenvolvimento , Medição de Risco , Temperatura Baixa , China , Monitoramento Ambiental/métodos
8.
Sci Total Environ ; 944: 173847, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38871325

RESUMO

The pine caterpillar (Dendrolimus spectabilis Bulter, Lepidoptera: Lasiocampidae), as an ectotherm, temperature plays a crucial role in its development. With climate change, earlier development of insect pests is expected to pose a more frequent threat to forest communities. Yet the quantitative research about the extent to which global warming affects pine caterpillar populations is rarely understood, particularly across various elevations and latitudes. Spring phenology of pine caterpillars showed an advancing trend with 0.8 d/10a, 2.2 d/10a, 2.2 d/10a, and 3.3 d/10a under the SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5 scenario, respectively. There was a maximum advance of 20 d in spring phenology of pine caterpillars during the 2090s, from mid-March to early March, and even late February. This study highlighted the significant advance in spring phenology at elevations >1000 m and lower latitudes. Consequently, the differences in elevational and latitudinal gradients were relatively small as the increasing temperatures at the end of the 21st century. And the average temperature in February-March was effective in explaining theses variability. These findings are crucial for adapting and mitigating to climate change.


Assuntos
Mudança Climática , Mariposas , Estações do Ano , Animais , Mariposas/fisiologia , Mariposas/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Altitude , Pinus , Temperatura
9.
BMC Genomics ; 25(1): 570, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844864

RESUMO

Compound eyes formation in decapod crustaceans occurs after the nauplius stage. However, the key genes and regulatory mechanisms of compound eye development during crustacean embryonic development have not yet been clarified. In this study, RNA-seq was used to investigate the gene expression profiles of Neocaridina denticulata sinensis from nauplius to zoea stage. Based on RNA-seq data analysis, the phototransduction and insect hormone biosynthesis pathways were enriched, and molting-related neuropeptides were highly expressed. There was strong cell proliferation in the embryo prior to compound eye development. The formation of the visual system and the hormonal regulation of hatching were the dominant biological events during compound eye development. The functional analysis of DEGs across all four developmental stages showed that cuticle formation, muscle growth and the establishment of immune system occurred from nauplius to zoea stage. Key genes related to eye development were discovered, including those involved in the determination and differentiation of the eye field, eye-color formation, and visual signal transduction. In conclusion, the results increase the understanding of the molecular mechanism of eye formation in crustacean embryonic stage.


Assuntos
Olho Composto de Artrópodes , Perfilação da Expressão Gênica , Animais , Olho Composto de Artrópodes/metabolismo , Olho Composto de Artrópodes/crescimento & desenvolvimento , Transcriptoma , Regulação da Expressão Gênica no Desenvolvimento , Decápodes/genética , Decápodes/crescimento & desenvolvimento , Olho/metabolismo , Olho/embriologia , Olho/crescimento & desenvolvimento
10.
Medicine (Baltimore) ; 103(23): e38460, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847730

RESUMO

RATIONALE: Mindfulness-Based Cancer Recovery (MBCR) program is a group course training for cancer patients that combines cancer knowledge and psychological knowledge, emphasizing focusing on the psychosomatic symptoms of cancer patients. Currently, the application value of Mindfulness-Based Cancer Recovery in improving psychosomatic health of cancer patients has been confirmed, however, its intervention effect on breast neoplasm patients has not yet been widely studied in China. PATIENT CONCERNS AND DIAGNOSES: This study introduced the Mindfulness-Based Cancer Recovery protocol into the rehabilitation process of breast cancer patients, aiming to elucidate the effects of Mindfulness-Based Cancer Recovery on anxiety, depression, post-traumatic stress disorder, and cancer-related fatigue in breast neoplasm patients, to provide a practical basis for improving the physical and mental health of breast cancer patients. INTERVENTION: In this study, 80 patients with chemotherapy-stage breast neoplasm attending the oncology department of a tertiary-level hospital from January 2022 to December 2022 were selected, 40 patients attending from January 2022 to June 2022 were included in the study group, and 40 patients attending from July 2022 to December 2022 were included in the control group. The control group was administered conventional care, and the study group was administered Mindfulness-Based Cancer Recovery based on conventional care in the control group for 8 weeks. After the intervention, hospital anxiety and depression scale, impact of event scale-revised, and cancer fatigue scale were used for evaluation. OUTCOMES: After the intervention, hospital anxiety and depression scale scores decreased in both groups compared with pre-intervention, with the study group scoring lower than the control group (P < .05). After the intervention, the impact of event scale-revised scores of the 2 groups decreased from the preintervention period, with the study group scoring lower than the control group (P < .05). After the intervention, cancer fatigue scale scores decreased in the 2 groups compared with the preintervention period, with the study group scoring lower than the control group (P < .05). LESSONS: Mindfulness-Based Cancer Recovery can effectively reduce the levels of anxiety, depression and post-traumatic stress disorder in breast neoplasm patients undergoing chemotherapy, reduce the levels of cancer-related fatigue, and promote the physical and mental health of patients.


Assuntos
Ansiedade , Neoplasias da Mama , Depressão , Fadiga , Atenção Plena , Transtornos de Estresse Pós-Traumáticos , Humanos , Atenção Plena/métodos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Fadiga/etiologia , Fadiga/terapia , Fadiga/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Ansiedade/etiologia , Ansiedade/terapia , Depressão/etiologia , Depressão/terapia , Depressão/psicologia , Adulto , China , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos
11.
Biology (Basel) ; 13(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38927246

RESUMO

Neocaridina denticulata sinensis has emerged as a promising model organism for basic studies in Decapod. However, the current transcriptome information on this species is based on next-generation sequencing technologies, which are limited by a short read length. Therefore, the present study aimed to generate a full-length transcriptome assembly of N. denticulata sinensis utilizing the PacBio Sequel Ⅱ platform. The resulting transcriptome assembly comprised 5831 transcripts with an N50 value of 3697 bp. Remarkably, 90.5% of these transcripts represented novel isoforms of known genes. The transcripts were further searched against the NR, SwissProt, KEGG, KOG, GO, NT, and Pfam databases. A total of 24.8% of the transcripts can be annotated across all seven databases. Additionally, 1236 alternative splicing events, 344 transcription factors, and 124 long non-coding RNAs (LncRNAs) were predicted. Based on the alternative splicing annotation results, a RING finger protein NHL-1 gene from N. denticulata sinensis (NdNHL-1) was identified. There are 15 transcripts in NdNHL-1. The longest transcript is 4995 bp in length and encodes a putative protein of 1665 amino acids. A phylogenetic analysis showed its close relationship with NHL-1 from other crustacean species. This report represents the full-length transcriptome of N. denticulata sinensis and will facilitate research on functional genomics and environmental adaptation in this species.

12.
Sci Total Environ ; 944: 173798, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38844236

RESUMO

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.


Assuntos
Apoptose , Cádmio , Trealase , Cádmio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Trealase/metabolismo , Trealase/genética , Poluentes Químicos da Água/toxicidade , Decápodes/fisiologia , Decápodes/genética
14.
J Org Chem ; 89(10): 7286-7294, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38696309

RESUMO

Here we report a carbene-catalyzed enantio- and diastereoselective [4+2] cycloaddition reaction of cyclobutenones with isatins for the quick and efficient synthesis of spirocyclic δ-lactones bearing a chiral chlorine. A broad range of substrates with various substitution patterns proceed smoothly in this reaction, with the spirooxindole δ-lactone products afforded in generally good to excellent yields and optical purities under mild reaction conditions.

15.
J Chem Inf Model ; 64(9): 3689-3705, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38676916

RESUMO

Combination therapy is a promising strategy for the successful treatment of cancer. The large number of possible combinations, however, mean that it is laborious and expensive to screen for synergistic drug combinations in vitro. Nevertheless, because of the availability of high-throughput screening data and advances in computational techniques, deep learning (DL) can be a useful tool for the prediction of synergistic drug combinations. In this study, we proposed a multimodal DL framework, MMSyn, for the prediction of synergistic drug combinations. First, features embedded in the drug molecules were extracted: structure, fingerprint, and string encoding. Then, gene expression data, DNA copy number, and pathway activity were used to describe cancer cell lines. Finally, these processed features were integrated using an attention mechanism and an interaction module and then input into a multilayer perceptron to predict drug synergy. Experimental results showed that our method outperformed five state-of-the-art DL methods and three traditional machine learning models for drug combination prediction. We verified that MMSyn achieved superior performance in stratified cross-validation settings using both the drug combination and cell line data. Moreover, we performed a set of ablation experiments to illustrate the effectiveness of each component and the efficacy of our model. In addition, our visual representation and case studies further confirmed the effectiveness of our model. All results showed that MMSyn can be used as a powerful tool for the prediction of synergistic drug combinations.


Assuntos
Aprendizado Profundo , Sinergismo Farmacológico , Humanos , Linhagem Celular Tumoral , Combinação de Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/química
16.
J Med Chem ; 67(9): 7330-7358, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38661655

RESUMO

The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinase-selective mTOR inhibitor 24 (PT-88), which demonstrated an mTOR inhibitory IC50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC50: 0.74 µM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.


Assuntos
Antineoplásicos , Neoplasias da Mama , Desenho de Fármacos , Inibidores de MTOR , Camundongos Nus , Serina-Treonina Quinases TOR , Triazinas , Humanos , Animais , Triazinas/síntese química , Triazinas/farmacologia , Triazinas/química , Triazinas/farmacocinética , Triazinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camundongos , Inibidores de MTOR/farmacologia , Inibidores de MTOR/síntese química , Inibidores de MTOR/uso terapêutico , Inibidores de MTOR/química , Relação Estrutura-Atividade , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Camundongos Endogâmicos BALB C , Autofagia/efeitos dos fármacos
17.
Mol Neurobiol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602654

RESUMO

Accumulating evidence strongly supports that PINK1 mutation can mediate mitochondrial autophagy dysfunction in dopaminergic neurons. This study was conducted to determine the role of PINK1 in the pathogenesis of postherpetic neuralgia (PHN) and find new targets for its treatment. A rigorous literature review was conducted to identify 2801 compounds from more than 200 plants in Asia. Virtual screening was used to shortlist the compounds into 20 groups based on their binding energies. MM/PBSA was used to further screen the compound dataset, and vitexin, luteoloside, and 2'-deoxyadenosine-5'-monophosphate were found to have a score of - 59.439, - 52.421, and - 47.544 kcal/mol, respectively. Pain behavioral quantification, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, western blotting, and transmission electron microscopy were used to confirm the effective mechanism. Vitexin had the most significant therapeutic effect on rats with PHN followed by luteoloside; 2'-deoxyadenosine-5'-monophosphate had no significant effect. Our findings suggested that vitexin could alleviate PHN by regulating mitochondrial autophagy through PINK1.

18.
Phytother Res ; 38(6): 2962-2992, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38600617

RESUMO

Neuropathic pain (NP) is a common chronic pain with heterogeneous clinical features, and consequent lowering of quality of life. Currently, although conventional chemical drugs can effectively manage NP symptoms in the short term, their long-term efficacy is limited, and they come with significant side effects. In this regard, traditional Chinese medicine (TCM) provides a promising avenue for treating NP. Numerous pharmacological and clinical studies have substantiated the effectiveness of TCM with multiple targets and mechanisms. We aimed to outline the characteristics of TCM, including compound prescriptions, single Chinese herbs, active ingredients, and TCM physical therapy, for NP treatment and discussed their efficacy by analyzing the pathogenesis of NP. Various databases, such as PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang database, were searched. We focused on recent research progress in NP treatment by TCM. Finally, we proposed the future challenges and emerging trends in the treatment of NP. TCM demonstrates significant clinical efficacy in NP treatment, employing multi-mechanisms. Drawing from the theory of syndrome differentiation, four types of dialectical treatments for NP by compound TCM prescriptions were introduced: promoting blood circulation and removing blood stasis; promoting blood circulation and promote Qi flow; warming Yang and benefiting Qi; soothing the liver and regulating Qi. Meanwhile, 33 single Chinese herbs and 25 active ingredients were included. In addition, TCM physical therapy (e.g., acupuncture, massage, acupoint injection, and fumigation) also showed good efficacy in NP treatment. TCM, particularly through the use of compound prescriptions and acupuncture, holds bright prospects in treating NP owing to its diverse holistic effects. Nonetheless, the multi-targets of TCM may result in possible disadvantages to NP treatment, and the pharmacological mechanisms of TCM need further evaluation. Here, we provide an overview of NP treatment via TCM, based on the pathogenesis and the potential therapeutic mechanisms, thus providing a reference for further studies.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Neuralgia , Humanos , Medicina Tradicional Chinesa/métodos , Neuralgia/tratamento farmacológico , Neuralgia/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Animais
19.
J Nat Med ; 78(3): 753-767, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38668831

RESUMO

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.


Assuntos
Analgésicos , Flores , Extratos Vegetais , Rhododendron , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Flores/química , Rhododendron/química , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Masculino , Dor/tratamento farmacológico , Cromatografia Líquida de Alta Pressão
20.
Front Public Health ; 12: 1351953, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450123

RESUMO

Objective: To investigate the connection between social support (SS) and successful aging (SA) in older adults residing in nursing homes, examining the mediating role of meaning in life (MIL). Additionally, this study aims to assess whether frailty moderates the mediation model. Methods: A cross-sectional survey approach was employed to recruit older adults from six nursing homes in Sichuan Province between August 2022 and December 2022. Questionnaires, including the General Information Questionnaire, Social Support Rating Scale (SSRS), Meaning in Life Questionnaire (MLQ), Tilburg Frailty Indicator (TFI), and Successful Aging Inventory (SAI), were administered. Data obtained from the completed questionnaires were analyzed using SPSS and its macro program PROCESS. Results: SS emerged as a noteworthy positive predictor of SA in older adults of nursing homes. MIL was identified as a partial mediator in the link between SS and SA. Furthermore, frailty attenuated the positive predictive impact of MIL on SA and moderated the latter part of the mediation model, wherein SS influences SA through MIL. The influence of MIL on SA was more pronounced in older adults with lower frailty levels in nursing homes, while it was diminished in those with higher levels of frailty. Conclusion: Apart from ensuring the availability of essential medical resources in long-term care for older adults, workers in nursing homes should also recognize the significance of "spiritual aging" to cultivate a sense of MIL among older adults. Simultaneously, attention must be directed toward screening for frailty indicators in older adults. Psychological care and physical exercise programs should be intensified for older adults with a high level of frailty, aiming to decelerate the progression of frailty in nursing home residents. This approach leverages the mediating role of MIL and the moderating influence of frailty, ultimately enhancing SA and promoting healthy aging in older adults within nursing home settings.


Assuntos
Fragilidade , Humanos , Idoso , Estudos Transversais , Casas de Saúde , Assistência de Longa Duração , Envelhecimento
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