Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.024
Filtrar
1.
Chem Commun (Camb) ; 60(19): 2677-2680, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38352990

RESUMO

An electrochemical multicomponent [2+2+1] cascade cyclization of enaminones and primary amines towards the synthesis of 4-acylimidazoles has been developed. In an undivided cell, enaminones and primary amines can smoothly participate in this reaction to provide a series of 1,2-disubstituted 4-acylimidazoles at room temperature. The reaction avoids the use of both transition-metal catalysts and oxidation reagents, which makes it more sustainable and renewable.

2.
World J Gastroenterol ; 30(5): 485-498, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38414591

RESUMO

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.


Assuntos
Ferroptose , Neoplasias Gástricas , Animais , Humanos , Ácidos e Sais Biliares , Transdução de Sinais
3.
Math Biosci Eng ; 21(1): 1394-1412, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303470

RESUMO

In response to the limited capability of extracting semantic information in knowledge graph completion methods, we propose a model that combines spatial transformation and attention mechanisms (STAM) for knowledge graph embedding. Firstly, spatial transformation is applied to reorganize entity embeddings and relation embeddings, enabling increased interaction between entities and relations while preserving shallow information. Next, a two-dimensional convolutional neural network is utilized to extract complex latent information among entity relations. Simultaneously, a multi-scale channel attention mechanism is constructed to enhance the capture of local detailed features and global semantic features. Finally, the surface-level shallow information and latent information are fused to obtain feature embeddings with richer semantic expression. The link prediction results on the public datasets WN18RR, FB15K237 and Kinship demonstrate that STAM achieved improvements of 8.8%, 10.5% and 6.9% in the mean reciprocal rank (MRR) evaluation metric compared to ConvE, for the respective datasets. Furthermore, in the link prediction experiments on the hydraulic engineering dataset, STAM achieves better experimental results in terms of MRR, Hits@1, Hits@3 and Hits@10 evaluation metrics, demonstrating the effectiveness of the model in the task of hydraulic engineering knowledge graph completion.

4.
Inorg Chem ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395040

RESUMO

The through-space charge transfer thermally activated delayed fluorescence (TSCT-TADF) properties of a series of molecules were characterized and tested theoretically by density functional theory and time-dependent density functional theory. By analyzing the weak interaction of the molecules at the ground state and calculating the transition contribution ratio of the donor, acceptor, and bridge in the excited state, we verified the through-space charge transfer characteristic of these molecules. We designed new molecules on the basis of the reported molecules (non-TADF molecule 1 and TADF molecule 2) to improve the performance. Smaller singlet-triplet energy gaps and larger spin-orbit coupling were obtained in the designed molecules, which is beneficial to obtain higher intersystem crossing and reverse intersystem crossing rates (kRISC). In addition, we calculated the radiation rate and the singlet-triplet reorganization energy, which is used to characterize the nonradiation rate. The comprehensive evaluation of both radiative and nonradiative processes shows that molecules 4 and 6 have the potential to be highly efficient TSCT-TADF materials.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38408006

RESUMO

CircRNA has been proved to play an important role in the diseases diagnosis and treatment. Considering that the wet-lab is time-consuming and expensive, computational methods are viable alternative in these years. However, the number of circRNA-disease associations (CDAs) that can be verified is relatively few, and some methods do not take full advantage of dependencies between attributes. To solve these problems, this paper proposes a novel method based on Kernel Fusion and Deep Auto-encoder (KFDAE) to predict the potential associations between circRNAs and diseases. Firstly, KFDAE uses a non-linear method to fuse the circRNA similarity kernels and disease similarity kernels. Then the vectors are connected to make the positive and negative sample sets, and these data are send to deep auto-encoder to reduce dimension and extract features. Finally, three-layer deep feedforward neural network is used to learn features and gain the prediction score. The experimental results show that compared with existing methods, KFDAE achieves the best performance. In addition, the results of case studies prove the effectiveness and practical significance of KFDAE, which means KFDAE is able to capture more comprehensive information and generate credible candidate for subsequent wet-lab.

6.
Materials (Basel) ; 17(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38399053

RESUMO

Cylinder liners, considered a crucial component of internal combustion (IC) engines, often require excellent mechanical properties to ensure optimal engine performance under elevated temperatures, pressures, and varying loads. In this work, a new low-alloy cylinder liner, incorporating a low content of molybdenum, copper, and chromium into gray cast iron, was fabricated using a centrifugal casting process. Subsequently, the heat treatment processes were designed to achieve bainite microstructures in the cylinder liner through rapid air cooling, isothermal transformation, and tempering. The effects of different air-cooling rates and tempering temperatures on the microstructure evolution and mechanical properties of cylinder liner were investigated. The results revealed that during the supercooled austenite transformation process, rapid air cooling at a rate of 14.5-23.3 °C/s can effectively bypass the formation of pearlitic structures and directly induce the formation of bainite structures. Once the temperature exceeded 480-520 °C, hardness and tensile strength increased with the temperature increase owing to the enhancement of the lower bainite content, the reduction of residual austenite, and the precipitation of the fine hard carbides in the matrix. With temperatures above 520-550 °C, the carbide and lower bainite organization coarsened, thereby reducing the hardness and tensile strength of the material. Therefore, the optimal heat treatment parameters were rapid cooling at 14.5-23.3 °C/s rate to obtain bainite, and tempering of 480-520 °C for finer and more uniform bainite. In addition, the results of the characterization of the mechanical properties of the cylinder liner after heat treatment showed that the hardness, tensile strength, and wear resistance were improved with the refinement of the bainite.

7.
Heliyon ; 10(3): e25162, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38322929

RESUMO

Background: The Delphi method has been extensively used to reach a consensus in traditional Chinese medicine (TCM) syndrome diagnosis research when subjective judgment is not uniform and objective evidence is lacking. The conduct and reporting of the Delphi method in TCM syndrome diagnosis research have never been critiqued. Our study aims to explore the consistency of using this technique and assess the reporting quality. Methods: A cross-sectional study was employed to scope articles reporting the conduct of the Delphi method in TCM syndrome diagnosis research. We searched the PubMed, Web of Science, CNKI, VIP, Wanfang and SinoMed databases with the restriction of Chinese and English language from their inception to March 25, 2023. A standardized extraction form was designed to collect demographics and methodological processes reflecting the rigor and transparency in TCM syndrome diagnosis research. Results: A total of 1832 studies were screened, and 50 were included. The median number of panels was 30 (IQR 20-34.5) and only 12 (24.0 %) studies were with a heterogeneous sample of panels. Two rounds was most common (37/50; 74.0 %), followed by three (7/50; 14.0 %), and only 13 (26.0 %) studies determined the number of rounds a priori. The reporting quality varied, with 18.0 % (9/50) reporting anonymity, 30.0 % (15/50) describing the controlled feedback, 20.0 % (10/50) reporting the procedure duration (7.14 ± 3.29 months) and 26.0 % (13/50) predefining the consensus. Conclusion: The Delphi method is inconsistently conducted and nontransparently reported in TCM syndrome diagnosis research. Standardized criteria are urgently needed for best practices in future research.

8.
Photodiagnosis Photodyn Ther ; 46: 104005, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38373470

RESUMO

Condyloma acuminatum (CA) is a sexually transmitted disease primarily caused by human papilloma virus (HPV) infection, predominantly affecting the genital and anal regions. However, the occurrence of oral condyloma acuminatum (OCA) is relatively infrequent, although its incidence has been gradually rising in recent years. OCA presents unique challenges in terms of treatment efficacy and recurrence prevention due to its concealed location and distinctive anatomical characteristics. In this manuscript, we present a case study involving the use of laser combined with photodynamic therapy (PDT) for managing hard palate OCA. The occurrence of warts in the hard jaw near the soft palate posed challenges during PDT due to involuntary swallowing and nausea. By modifying the conventional PDT approach and replacing the dressing with a cotton swab, the patient experience is more comfortable and therapeutic outcomes is more effective. Remarkably, the procedure resulted in minimal scarring post-operation. The combined approach of laser and PDT demonstrates promising results as a rapid and well-tolerated treatment modality for OCA.

9.
Heliyon ; 10(3): e25267, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327400

RESUMO

Background: Xingnaojing (XNJ) injection, an extract derived from traditional Chinese medicine, is commonly used to treat ischemic stroke (IS). Previous studies have shown that XNJ has the ability to alleviate apoptosis in cerebral ischemia-reperfusion injury. However, the potential mechanisms have not been clarified. Objective: To identify the neuroprotective effect of XNJ and explore whether XNJ inhibits cell apoptosis associated with endoplasmic reticulum stress (ERS) after IS. Methods: In this study, cultured hippocampal neurons from mouse embryos and Sprague-Dawley rats were assigned randomly to four groups: sham, model, XNJ, and edaravone. The treatment groups were administered 2 h after modelling. Neurological deficit scores and motor performance tests were performed after 24 h of modelling. Additionally, pathomorphology, cell apoptosis and calcium content were evaluated. To ascertain the expression of ERS proteins, western blotting and polymerase chain reaction were employed. Results: The results indicated that XNJ treatment resulted in a notable decrease in infarct volume, apoptosis and missteps compared with the model group. XNJ also exhibited improvements in neurological function, grip strength and motor time. The calcium content significantly reduced in XNJ group. The XNJ administration resulted in a reduction in the levels of proteins associated with ERS including CHOP, GRP78, Bax, caspase-12, caspase-9, and cleaved-caspase-3, but an increase of the Bcl-2/Bax ratio. Furthermore, the downregulation of mRNA expression of CHOP, GRP78, caspase-12, caspase-9, and caspase-3 was confirmed in both cultured neurons and rat model. Conclusion: These findings suggest that XNJ may alleviate apoptosis by modulating the ERS-induced apoptosis pathway, making it a potential novel therapeutic approach for ischemic stroke.

10.
Parkinsons Dis ; 2024: 3651705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356939

RESUMO

Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively. Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (ß = 0.869, P < 0.001) and the preoperative attention/memory subscore (ß = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL). Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

11.
J Hazard Mater ; 468: 133712, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38377917

RESUMO

To reduce the number of sensors in the SCR catalyst, state feedback and fault diagnosis information are provided. Firstly, a model based on the coupling of flow, heat transfer, and gas-solid phase catalytic reaction in the SCR system is investigated in this paper. The parabolic partial differential equations are simplified by the variable substitution method and the method of lines approach (MOL). The simplified system of equations is solved by backward differentiation formulas (BDF) with adaptive adjustment time step strategy. Meanwhile, the chemical reaction parameters are accurately calibrated per second using the Levenberg-Marquardt method. Secondly, the ATS-UKF is designed in this paper, and to ensure the synchronisation between the ATS-UKF and the SCR model calculations, the time step of solving the BDF by the SCR model is taken as the time step of propagating the sigma points. Two observation scenarios are assumed: (1) no downstream NH3 concentration sensor, ammonia coverage and downstream NH3 concentration are observed by ATS-UKF; (2) no downstream NOx sensor, ammonia coverage and downstream NOx concentration are observed by ATS-UKF. Finally, the paper carries out bench tests. In the first case, the ammonia coverage obtained by the ATS-UKF reached 0.99 with respect to the model-calculated value R². The mean absolute error (MAE) between the observed and experimental values of the ATS-UKF for the downstream NH3 concentration was 2.76 ppm. In the second case, the ammonia coverage obtained by the ATS-UKF reached 0.99 with respect to the model-calculated value R², and the MAE between the observed and experimental values of the ATS-UKF for the downstream NOx concentration was 1.53 ppm. ENVIRONMENTAL IMPLICATION: The Adaptive Time-Step Unscented Kalman Filtering (ATS-UKF) enhances urea Selective Catalytic Reduction (SCR) in diesel engines, improving environmental outcomes. This method minimizes sensor dependence, enabling more precise SCR system management and effective emission reduction. By advancing emission control technologies, ATS-UKF contributes to global air pollution mitigation efforts, supporting cleaner air and environmental sustainability. Its innovative approach in monitoring and predicting SCR performance marks a significant step towards eco-friendly diesel engine operation.

12.
Drug Dev Res ; 85(1): e22142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38349266

RESUMO

Thyroid cancer is a highly differentiated and poorly malignant tumor. Interfering with glycolysis has become an effective means of controlling cancer progression and autophagy is negatively correlated with glycolysis. Aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated to be highly expressed in thyroid cancer tissue and the higher AKR1C3 expression predicted the worse prognosis. We aimed to explore whether AKR1C3 could affect thyroid cancer progression by regulating autophagy-dependent glycolysis. AKR1C3 expression in thyroid cancer cells was detected by western blot. Then, AKR1C3 was knocked down by transfection with short hairpin RNA specific to AKR1C3 in the absence or presence of 3-methyladenine (3-MA) or PMA treatment. Cell cycle and apoptosis was detected by flow cytometry. Immunofluorescence staining was used to analyze LC3B expression. Extracellular acidification, glucose uptake and lactic acid secretion were detected. To evaluate the tumorigenicity of AKR1C3 insufficiency on thyroid cancer in vivo, TPC-1 cells with AKR1C3 knockdown were injected subcutaneously into nude mice. Then, cyclinD1 and Ki67 expression in tumorous tissues was measured by immunohistochemical analysis. Apoptosis was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling staining. Additionally, the expression of proteins related to cell cycle, apoptosis, glycolysis, autophagy, and extracellular signal-regulated kinase (ERK) signaling in cells and tumor tissues was assessed by western blot. Highly expressed AKR1C3 was observed in thyroid cancer cells. AKR1C3 knockdown induced cell cycle arrest and apoptosis of TPC-1 cells. Besides, autophagy was activated and glycolysis was inhibited following AKR1C3 silencing, and 3-MA treatment restored the impacts of AKR1C3 silencing on glycolysis. The further experiments revealed that AKR1C3 insufficiency inhibited ERK signaling and PMA application reversed AKR1C3 silencing-induced autophagy in TPC-1 cells. The in vivo results suggested that AKR1C3 knockdown inhibited the development of subcutaneous TPC-1 tumors in nude mice and inactivated the ERK signaling. Collectively, AKR1C3 silencing inhibited autophagy-dependent glycolysis in thyroid cancer by inactivating ERK signaling.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Neoplasias da Glândula Tireoide , Animais , Camundongos , Membro C3 da Família 1 de alfa-Ceto Redutase , Autofagia , Glicólise , Camundongos Nus , Neoplasias da Glândula Tireoide/genética , Humanos
13.
Nat Chem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326646

RESUMO

DNA-encoded chemical libraries (DELs) have become a powerful technology platform in drug discovery. Dual-pharmacophore DELs display two sets of small molecules at the termini of DNA duplexes, thereby enabling the identification of synergistic binders against biological targets, and have been successfully applied in fragment-based ligand discovery and affinity maturation of known ligands. However, dual-pharmacophore DELs identify separate binders that require subsequent linking to obtain the full ligands, which is often challenging. Here we report a protein-templated DEL selection approach that can identify full ligand/inhibitor structures from DNA-encoded dynamic libraries (DEDLs) without the need for subsequent fragment linking. Our approach is based on dynamic DNA hybridization and target-templated in situ ligand synthesis, and it incorporates and encodes the linker structures in the library, along with the building blocks, to be sampled by the target protein. To demonstrate the performance of this method, 4.35-million- and 3.00-million-member DEDLs with different library architectures were prepared, and hit selection was achieved against four therapeutically relevant target proteins.

14.
Asia Pac Psychiatry ; 16(1): e12552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38348641

RESUMO

BACKGROUND: Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. METHODS: Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. RESULTS: Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; ß = .4457, 95% CI = 0.0780-1.0253, c-path; ß = .2447, p = .0260, c'-path; ß = -.2009, p = .3427). CONCLUSIONS: These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.


Assuntos
Transtorno Depressivo Maior , Humanos , Depressão , Sistema Hipotálamo-Hipofisário , Hidrocortisona , Grelina , Sistema Hipófise-Suprarrenal
15.
Support Care Cancer ; 32(3): 146, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38326575

RESUMO

OBJECTIVES: The purpose of this study was to explore the experience of financial toxicity among caregivers of cancer patients and to provide recommendations for subsequent intervention strategies. METHODS: Computer searches of PubMed, EmBase, The Cochrane Library, Web of Science, CINAHL (EBSCO), CNKI, Wanfang database, and SinoMed for qualitative studies experience of financial toxicity among caregivers cancer patients. The search time frame was from the establishment of the database to May 2023. The quality of included studies was assessed using the Qualitative Research Checklist from the Joanna Briggs Institute (JBI) Reviewer's Manual. The meta-synthesis was integrated following the meta-aggregation method proposed by the Joanna Briggs Institute (JBI) and reported following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. RESULTS: A total of nine studies were included, distilling 25 qualitative findings into nine new categories and synthesizing three synthesized findings: caregivers have strong negative experiences that affect their family relationships, daily work and life; caregivers use different strategies to cope with financial toxicity; needs and expectations of caregivers coping with financial toxicity. CONCLUSIONS: Financial toxicity among caregivers of cancer patients affects their daily lives. Receiving timely recognition of this financial burden and providing assistance to enhance their coping skills are crucial in mitigating its impact. Healthcare professionals should focus on the financial toxicity experienced by caregivers of people with cancer, address their supportive needs, and develop a comprehensive support system to improve caregivers' coping abilities and quality of life.


Assuntos
Cuidadores , Neoplasias , Humanos , Estresse Financeiro , Qualidade de Vida , Pesquisa Qualitativa , Neoplasias/terapia
16.
FASEB J ; 38(4): e23476, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334392

RESUMO

The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/ß-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed ß-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/ß-catenin in the epidermis prompted telogen-anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.


Assuntos
Folículo Piloso , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Folículo Piloso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Endotelina-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Cultivadas , Proliferação de Células , Epiderme/metabolismo , Alopecia/metabolismo , Via de Sinalização Wnt , Derme/metabolismo , Citocinas/metabolismo
17.
Eur J Obstet Gynecol Reprod Biol ; 295: 219-227, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38387304

RESUMO

INTRODUCTION: Premature menopause is a major complication of primary ovarian insufficiency (POI), and this loss is closely relates to bone mineral density (BMD). Previous research has indicated potential associations between BMD and POI. This study set out to provide the first systematic literature review and meta-analysison account of BMD content among women with POI. METHODS: Studies including women with POI and controls were eligible from PubMed, Embase, Cochrane Library and Web of Science databases (from their inception to April 2022). Two reviewers independently evaluated study eligibility. The meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS: Ten studies featuring 578 women with POI and 480 controls were selected. BMD content of femur neck (SMD:-0.76; 95 % CI: -1.20 to -0.31; P = 0.0008), the BMD content of nondominating forearm (SMD:-0.67; 95 % CI: -1.15 to -0.18; P = 0.007) were significantly decreased in women with POI. However, no differences were seen in other regions (lumbar spine, total hip, hipneck). DISCUSSION: The results of this study indicate that BMD content altered in patients with primary ovarian insufficiency. An implication of this is the possibility that hormone replacement therapy to minimize the prevalence of fracture morbidity and mortality associated with osteopenia in patients with POI.

18.
Mol Carcinog ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390729

RESUMO

Golgi phosphoprotein 3 (GOLPH3) has been reported as an oncogene in various tumors; however, the role and function of GOLPH3 and its relevant molecular mechanism in cholangiocarcinoma (CCA) are unclear. Herein, GOLPH3 expression in CCA tissues was observed to be significantly higher than that in paired adjacent noncancerous tissues. Clinicopathological analysis showed that GOLPH3 expression correlated positively with the tumor-node-metastasis stage. In addition, GOLPH3 expression correlated inversely with the overall survival of patients with CCA. Multivariate analysis showed that GOLPH3 was an independent prognostic factor for patients with CCA. Transcriptome analysis (RNA sequencing) of GOLPH3 knockdown cells showed that the expression levels of nine ferroptosis-related genes were significantly changed, indicating the important biological function of GOLPH3 in ferroptosis in CCA cells. Furthermore, GOLPH3 knockdown could significantly promote Erastin-induced ferroptosis in vitro and suppress tumor growth in vivo. Overexpression of GOLPH3 had the opposite effect on this phenotype. Further studies revealed that GOLPH3 knockdown was significantly associated with a decrease in cysteine content, an accumulation of the lipid peroxidation product malondialdehyde, an increase in reactive oxygen species, and sensitized CCA cells to Erastin-induced ferroptosis. Moreover, changes in GOLPH3 expression were found to be consistent with the expression of light chain subunit solute carrier family 7 member 11 (SLC7A11). Thus, our study suggested that GOLPH3 functions as an oncoprotein in CCA and may suppress ferroptosis by facilitating SLC7A11 expression, suggesting that GOLPH3 could serve as a therapeutic target for CCA treatment.

19.
RSC Adv ; 14(10): 6508-6520, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38390513

RESUMO

Produced gas re-injection is an effective and eco-friendly approach for enhancing oil recovery from shale oil reservoirs. However, the interactions between different gas phase components, and the oil phase and rocks are still unclear during the re-injection process. This study aims to investigate the potential of produced gas re-injection, particularly focusing on the effects of methane (CH4) content in the produced gas on shale oil displacement. Molecular dynamics simulations were employed to analyze the interactions between gas, oil, and matrix phases with different CH4 proportions (0%, 25%, 50%, and 100%), alkanes and under various burial depth. Results show that a 25% CH4 content in the produced gas achieves almost the same displacement effect as pure carbon dioxide (CO2) injection. However, when the CH4 content increases to 50% and 100%, the interaction between gas and quartz becomes insufficient to effectively isolate oil from quartz, causing only expansion and slight dispersion. Interestingly, the presence of CH4 has a synergistic effect on CO2, facilitating the diffusion of CO2 into the oil film. During the gas stripping process, CO2 is the main factor separating oil from quartz, while CH4 mainly contributes to oil expansion. In addition, for crude oil containing a large amount of light alkanes, extracting light components through mixed gas may be more effective than pure CO2. This study offers valuable insights for applications of produced gas re-injection to promote shale oil recovery.

20.
Int J Biol Macromol ; 263(Pt 2): 130245, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38367779

RESUMO

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of ßPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of ßPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and ßPS integrins and partially rescued the detachment phenotype in flies with reduced ßPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...