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1.
Adv Mater ; : e2210909, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36708237

RESUMO

Moiré superlattices in twisted van der Waals materials offer a powerful platform for exploring light-matter interactions. The periodic moiré potentials in moiré superlattices can induce strongly correlated quantum phenomena such as moiré excitons, superconductivity and the Mott-insulating state, all of which depend on the moiré potential associated with the interlayer coupling at the interface. However, moiré superlattices are primarily prepared by the mechanical exfoliation technique and the manual stacking method, where the transfer methods easily cause interfacial contamination, and the preparation of high-quality bilayer two-dimensional materials with small twist angles by direct growth methods remains a significant challenge. Here, we synthesized the WSe2 /WSe2 homobilayer with different twist angles by a CVD method using a heteroatom-assisted growth technique. Using the low-frequency Raman scattering, the uniformity of the moiré superlattices were mapped to demonstrate the strong interfacial coupling of the CVD-fabricated twist-angle homobilayer. The moiré potential depths of the CVD-grown and artificially stacked homostructures with twist angles of 1.5° were 115 and 45 meV (an increased of 155%), indicating that the depth of the moiré potential can be modulated by the interfacial coupling. Our results open a new avenue to study the modulation of moiré potential by strong interlayer coupling and provide a foundation for the development of twistronics . This article is protected by copyright. All rights reserved.

2.
Gastric Cancer ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602696

RESUMO

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer. METHODS: Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1. RESULTS: HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p. CONCLUSIONS: The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer.

3.
Life Sci Alliance ; 6(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36690443

RESUMO

Store-operated Ca2+ entry (SOCE) is a universal Ca2+ influx pathway that is important for the function of many cell types. SOCE is controlled by the interaction of the ER Ca2+ sensor STIM1 with the plasma membrane Ca2+ channel Orai1. S417 is located in the third coiled-coil (CC3) domain of the C-terminus of STIM1. We found that single-point mutation of this residue (S417G) abolished STIM1 C-terminus interactions with Orai1. Mutation of S417 also abolished CAD-Orai1 binding and Orai1 channel activation, eliminated STIM1 puncta formation, and co-localization with Orai1 and SOCE. 2-APB was found to restore the binding of the STIM1 C-terminus mutant (S417G) to Orai1 and dose-dependently activate Orai1 channel. Both CBD and NBD of Orai1 are required for 2-APB-induced coupling between the Orai1 and STIM1 C-terminus mutant (S417G) and CRAC channel activation. We also demonstrated that 2-APB led to delayed activation of Orai1-K85E channel, although Orai1-K85E obviously impairs 2-APB-induced STIM1 C-terminus mutant (S417G)-Orai1 coupling. Our results suggest S417 in the CC3 domain of STIM1 is essential for STIM1-Orai1 binding and CRAC channel activation.


Assuntos
Canais de Cálcio , Canais de Cálcio Ativados pela Liberação de Cálcio , Canais de Cálcio/genética , Proteínas de Membrana/metabolismo , Proteína ORAI1 , Membrana Celular/metabolismo
4.
Foods ; 12(2)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36673389

RESUMO

This study attempts to explore the suitable conditions for the detection of volatile flavor compounds (VFCs) in Ningxiang pork by headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GC-MS). Ningxiang pigs were harvested from a slaughterhouse and a longissimus dorsi sample was collected from each animal. The VFCs of Ningxiang pork can be strongly impacted by the detection conditions (columns, weight of meat samples, heat treatment time, equilibrium conditions, and extraction conditions) that need to be optimized. Our results also provided the optimal test conditions: weighing 5 g of meat samples, grinding for 30 s in a homogenizer, heat treatment at 100 °C for 30 min, equilibration at 70 °C for 30 min, and extraction at 100 °C for 50 min. Furthermore, the feasibility and representativeness of the test method were confirmed based on principal component analysis and a comparison of the three pork VFCs. These findings offer researchers a unified and efficient pretreatment strategy to research pork VFCs.

5.
Small ; : e2207266, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693790

RESUMO

Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking. Herein, the assembly using 1,4-dicarboxylbenzene-2,3-dithiol (H2 dcbdt) and Zr-Oxo clusters to give a thiol-functionalized UiO-66 type framework, UiO-66-dcbdt, is reported. The thiocatechols on the struts are allowed to capture transition metal (TM) ions to generate UiO-66-dcbdt-M (M  = Fe, Ni, Cu) with unambiguous metal-thiocatecholate moieties for photocatalytic hydrogen evolution reaction (HER). UiO-66-dcbdt-Cu is found the best catalyst exhibiting an HER rate of 4.18 mmol g-1  h-1  upon irradiation with photosensitizing Ru-polypyridyl complex. To skip the use of the external sensitizer, UiO-66-dcbdt-Cu is heterojunctioned with titanium dioxide (TiO2 ) and achieves an HER rate of 12.63 mmol g-1  h-1  (32.3 times that of primitive TiO2 ). This work represents the first example of MOF assembly employing H2 dcbdt as the mere linker followed by chelation with TM ions and undoubtedly fuels the rational design of MOF photocatalysts bearing well-defined active sites.

6.
J Agric Food Chem ; 71(3): 1477-1487, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36642968

RESUMO

Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEV-induced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced intestinal epithelial cell pyroptosis and reduces intestinal injury in TGEV-infected piglets. Mechanistically, eugenol reduces the activation of NLRP3 inflammasome, thereby inhibiting TGEV-induced intestinal epithelial cell pyroptosis. In addition, eugenol scavenges TGEV-induced reactive oxygen species (ROS) increase, which in turn prevents TGEV-induced NLRP3 inflammasome activation and pyroptosis. Overall, eugenol protects the intestine by reducing TGEV-induced pyroptosis through inhibition of NLRP3 inflammasome activation, which may be mediated through intracellular ROS levels. These findings propose that eugenol may be an effective strategy to prevent TGEV infection.


Assuntos
Vírus da Gastroenterite Transmissível , Animais , Eugenol/farmacologia , Inflamassomos/genética , Intestinos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Piroptose , Espécies Reativas de Oxigênio , Suínos , Vírus da Gastroenterite Transmissível/fisiologia , Proteínas de Ligação a Fosfato/metabolismo , /metabolismo
7.
Front Pharmacol ; 14: 1067089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713843

RESUMO

Terminalia chebula Retz. (TC) is a well-known Chinese herbal medicine and rich in chemical components with multiple pharmacological effects. In this study, an ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed and used to determine the blood concentrations of nine active compounds (chebulic acid, gallic acid, protocatechuic acid, corilagin, chebulagic acid, chebulinic acid, 1,2,3,4,6-O-pentagalloylglucose, ellagic acid and ethyl gallate) after oral administration of TC extracts in rats. Pretreatment of plasma samples with protein precipitate with methanol was carried out, and caffeic acid was used as the internal standard (IS). Compounds precisions of intra- and inter-day were less than 14.6%, and the accuracy ranged from -11.7% to 13.5%. The extraction recoveries of compounds were between 84.9% and 108.4%, while matrix effects occurred between 86.4% and 115.9%. Stability tests showed that all nine analytes had been stable under four storage conditions, and statistically significant the relative standard deviations were under 13.7%. The validated UPLC-MS/MS method was applied with great success to plasma pharmacokinetics analysis of the TC extracts, and the pharmacokinetic results showed that among the nine components, the area under the concentration-time curve (AUC(0-tn), 231112.38 ± 64555.20 h ng/mL) and maximum concentration (Cmax, 4,983.57 ± 1721.53 ng/mL) of chebulagic acid were relatively large, which indicated that it had a higher level of plasma exposure. The half-life of elimination (T1/2) of chebulinic acid, corilagin and chebulagic acid were 43.30, 26.39 and 19.98 h, respectively, suggesting that these analytes showed prolonged retention and metabolize more slowly in vivo. This study would deliver a theoretical foundation for the further application of TC in clinical practice.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36716512

RESUMO

Zanthoxyli Radix, the dried root of Zanthozylum nitidum (Roxb.) DC, one of traditional Chinese medicines (TCMs), exhibits various pharmacological activities such as anti-bacterial, anti-inflammatory, anti-tumor, analgesic activity. A sustainable vortex-enhanced magnetic solid phase extraction (VE-MSPE) method combined with ultra-high performance liquid chromatography (UHPLC) was established to enrich and analyze the bioactive quaternary ammonium alkaloids (QAAs) of Zanthoxyli Radix. Fe3O4@C@CMCS magnetic nanoparticles (MNPs) was first synthesized for selectively adsorbing target QAAs (magnolinine, sanguinarine, nitidine chloride and chelerythrine), which possess excellent adsorption performance after being reused 10 times. The results revealed that the great adsorption rate of Fe3O4@C@CMCS MNPs for the four QAAs could reach 55.1-78.7 %. In addition, a reliable linear relationship (r ≥ 0.9995) and good recovery (97.5-104 %) was obtained. Consequently, the VE-MSPE method applying Fe3O4@C@CMCS MNPs as a sustainable adsorbent exhibited great potential in the selective enrichment of QAAs in TCM.

9.
J Investig Med ; : 10815589221143739, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36718830

RESUMO

To analyze the heterogeneity between different cell types in pediatric Wilms tumor (WT) tissue, and identify the differentially expressed genes (DEGs) of malignant tumor cells, thereby establishing a prognostic model. The single-cell sequencing data of pediatric WT tissues were downloaded from the public database. Data filtration and normalization, principal component analysis, and T-distributed stochastic neighbor embedding cluster analysis were performed using the Seurat package of R language. Cells were divided into different clusters, malignant tumor cells were extracted, and DEGs were obtained. Then, the pseudo-time trajectory analysis was performed. Prognostic biomarkers were determined by univariate and multivariate COX regression analyses and LASSO regression analysis. Kaplan-Meier survival analysis and receiver operator characteristic curve analysis were performed. Combined with the prognostic biomarkers and clinical characteristics, a nomogram was generated to predict WT prognosis. The prognostic power was validated in the external datasets. Cells in the WT tissue were divided into 10 clusters. Three prognostic biomarkers that affected the survival time of patients were screened from 215 DEGs in malignant tumor cells, and a nomogram was constructed using the three genes and clinical characteristics. The area under the curve (AUC) values of 3- and 5-year disease-free survival were 0.756 and 0.734, respectively. In the external validation dataset, the AUC value of this nomogram model was 0.826. Based on the single-cell RNA-seq, we recognized cell clusters in the WT tissue of children, identified prognostic biomarkers in malignant tumor cells, and established a comprehensive prognostic model. Our findings might provide new ideas and methods for the diagnosis and treatment of WT.

10.
Semin Oncol ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36693773

RESUMO

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher's exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus.

11.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633127

RESUMO

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that cell migration assay data shown in Figs. 2C and 5D were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3948­3954, 2019; DOI: 10.3892/mmr.2019.10013].

12.
Int J Biol Macromol ; 230: 123147, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621729

RESUMO

Photodynamic therapy is a promising novel tumor treatment method. In this study, novel porphyrin-chrysin photosensitizer derivatives were synthesized. Most of the compounds showed antitumor activity against human cervical cancer HeLa cells and human lung cancer A549 cells, among which compound 4c had the best photodynamic therapy effect on HeLa cells and A549 cells, with IC50 values of 6.26 µM and 23.37 µM, respectively. Free-base porphyrin-chrysin derivatives bind to DNA through surface self-stacking, and zinc metalloporphyrin-chrysin derivatives bind to ct-DNA through intercalation. Notably, the tightness of compound binding to ct-DNA was positively correlated with its antitumor activity. What's more, three-dimensional quantitative conformation studies have shown that increasing the positive charge of the porphyrin ring and introducing a strong electron-withdrawing group at the meso position of the porphyrin ring at the para-position of the benzene ring or reducing the space volume of the compound can enhance the antitumor activity.

13.
Opt Lett ; 48(2): 452-455, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638481

RESUMO

We demonstrate a novel, to the best of our knowledge, two-dimensional vector bending sensor based on orthogonal helical Bragg gratings inscribed in the cladding of a conventional single-mode fiber (SMF). The helical cladding fiber Bragg gratings (HCFBGs) are created by using a femtosecond laser direct writing technology and a quarter-pitch graded index fiber (GIF) is used in front of the HCFBGs to diverge the core mode into fiber cladding. In contrast to the multimode resonance observed in conventional cladding Bragg gratings inscribed by using a femtosecond laser point-by-point (PbP) or line-by-line (LbL) technology, the proposed HCFBGs exhibit stable narrowband single-mode Bragg resonance. An HCFBG with a low peak reflectivity of -50.77 dB and a narrow bandwidth of 0.66 nm was successfully fabricated by using a lateral offset of 45 µm between the HCFBG and the fiber core axis. Moreover, two orthogonal HCFBGs were fabricated in the SMF cladding and used for vector bending sensing. Strong orientation dependence could be seen in omnidirectional bending measurement, exhibiting a maximum bending sensitivity of up to 50.0 pm/m-1, which is comparable to that in a multicore FBG. In addition, both the orientation and amplitude of bending vector could be reconstructed by using the measured Bragg wavelength shifts in two orthogonal HCFBGs. As such, the proposed HCFBGs could be used in many applications, such as structural health monitoring, robotic arms, and medical instruments.

14.
Phytomedicine ; 111: 154654, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36689857

RESUMO

BACKGROUND: Hypericin is a prominent secondary metabolite mainly existing in genus Hypericum. It has become a research focus for a quiet long time owing to its extensively pharmacological activities especially the anti-cancer, anti-bacterial, anti-viral and neuroprotective effects. This review concentrated on summarizing and analyzing the existing studies of hypericin in a comprehensive perspective. METHODS: The literature with desired information about hypericin published after 2010 was gained from electronic databases including PubMed, SciFinder, Science Direct, Web of Science, China National Knowledge Infrastructure databases and Wan Fang DATA. RESULTS: According to extensive preclinical and clinical studies conducted on the hypericin, an organized and comprehensive summary of the natural and artificial sources, strategies for improving the bioactivities, pharmacological activities, drug combination of hypericin was presented to explore the future therapeutic potential of this active compound. CONCLUSIONS: Overall, this review offered a theoretical guidance for the follow-up research of hypericin. However, the pharmacological mechanisms, pharmacokinetics and structure activity relationship of hypericin should be further studied in future research.

15.
Mol Plant Pathol ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692022

RESUMO

Citrus huanglongbing (HLB), associated with the unculturable phloem-limited bacterium "Candidatus Liberibacter asiaticus" (CLas), is the most devastating disease in the citrus industry worldwide. However, the pathogenicity of CLas remains poorly understood. In this study, we show that AGH17488, a secreted protein encoded by the prophage region of the CLas genome, suppresses plant immunity via targeting the host ASCORBATE PEROXIDASE6 (APX6) protein in Nicotiana benthamiana and Citrus sinensis. The transient expression of AGH17488 reduced the chloroplast localization of APX6 and its enzyme activity, inhibited the accumulation of reactive oxygen species (H2 O2 and O2 - ) and the lipid oxidation endproduct malondialdehyde in plants, and promoted the proliferation of Pseudomonas syringae pv. tomato DC3000 and Xanthomonas citri subsp. citri. This study reveals a novel mechanism underlying how CLas uses a prophage-encoded effector, AGH17488, to target a reactive oxygen species accumulation-related gene, APX6, in the host to facilitate its infection.

16.
Cogn Neurodyn ; 17(1): 203-220, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36704630

RESUMO

Studies have shown that Parkinson's, epilepsy and other brain deficits are closely related to the ability of neurons to synchronize with their neighbors. Therefore, the neurobiological mechanism and synchronization behavior of neurons has attracted much attention in recent years. In this contribution, it is numerically investigated the complex nonlinear behaviour of the Hindmarsh-Rose neuron system through the time responses, system bifurcation diagram and Lyapunov exponent under different system parameters. The system presents different and complex dynamic behaviors with the variation of parameter. Then, the identification of the nonlinear dynamics and topologies of the Hindmarsh-Rose neural networks under unknown dynamical environment is discussed. By using the deterministic learning algorithm, the unknown dynamics and topologies of the Hindmarsh-Rose system are locally accurately identified. Additionally, the identified system dynamics can be stored and represented in the form of constant neural networks due to the convergence of system parameters. Finally, based on the time-invariant representation of system dynamics, a fast dynamical pattern recognition method via system synchronization is constructed. The achievements of this work will provide more incentives and possibilities for biological experiments and medical treatment as well as other related clinical researches, such as the quantifying and explaining of neurobiological mechanism, early diagnosis, classification and control (treatment) of neurologic diseases, such as Parkinson's and epilepsy. Simulations are included to verify the effectiveness of the proposed method.

17.
Clin Chem ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683393

RESUMO

BACKGROUND: The aim is to evaluate the clinical utility of a long-read sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in prenatal diagnosis of thalassemia. METHODS: A total of 278 fetuses from at-risk pregnancies identified in thalassemia carrier screening by PCR-based methods were recruited from 9 hospitals, and PCR-based methods were employed for prenatal diagnosis. CATSA was performed retrospectively and blindly for all 278 fetuses. RESULTS: Among the 278 fetuses, 263 (94.6%) had concordant results and 15 (5.4%) had discordant results between the 2 methods. Of the 15 fetuses, 4 had discordant thalassemia variants within the PCR detection range and 11 had additional variants identified by CATSA. Independent PCR and Sanger sequencing confirmed the CATSA results. In total, CATSA and PCR-based methods correctly detected 206 and 191 fetuses with variants, respectively. Thus, CATSA yielded a 7.9% (15 of 191) increment as compared with PCR-based methods. CATSA also corrected the predicted phenotype in 8 fetuses. Specifically, a PCR-based method showed one fetus had homozygous HBB c.52A > T variants, while CATSA determined the variant was heterozygous, which corrected the predicted phenotype from ß-thalassemia major to trait, potentially impacting the pregnancy outcome. CATSA additionally identified α-globin triplicates in 2 fetuses with the heterozygous HBB c.316-197C > T variant, which corrected the predicted phenotype from ß-thalassemia trait to intermedia and changed the disease prognosis. CONCLUSIONS: CATSA represents a more comprehensive and accurate approach that potentially enables more informed genetic counseling and improved clinical outcomes compared to PCR-based methods.

18.
ChemSusChem ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624051

RESUMO

Metal halide perovskite solar cells (PSCs) have been showing up in the commercial field, with an inspiring power conversion efficiency (PCEs) of over 26% in the laboratory. The quality of perovskite films is still a bottleneck due to the random and fast crystallization of ionic perovskite materials. Seeding agents mediated crystallization has consistently been recognized as an efficient method for preparing bulk single crystals and high-quality films. Herein, we summarized the seeding mechanism, characterization techniques, and seeding agents working in different locations during the PSCs device fabrication. This review could further facilitate researchers with a deeper understanding of seeding agents and enhance more choices for seeding crystallization to improve the performance further and the device's large-scale fabrication toward commercialization.

19.
J Pathol ; 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36640260

RESUMO

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a dedifferentiated (proliferative) phenotype contributes to neointima formation, which has been demonstrated to possess a tumour-like nature. Dysregulated glucose and lipid metabolism is recognized as a hallmark of tumours but has not thoroughly been elucidated in neointima formation. Here, we investigated the cooperative role of glycolysis and fatty acid synthesis in vascular injury-induced VSMC dedifferentiation and neointima formation. We found that the expression of hypoxia-inducible factor-1α (HIF-1α) and its target 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), a critical glycolytic enzyme, were induced in the neointimal VSMCs of human stenotic carotid arteries and wire injured mouse carotid arteries. HIF-1α overexpression to elevate glycolysis resulted in a decreased contractile phenotype while promoting VSMC proliferation and mTORC1 activation. Conversely, silencing Pfkfb3 had the opposite effects. Mechanistic studies demonstrated that glycolysis generates acetyl coenzyme A to fuel de novo fatty acid synthesis and mTORC1 activation. Whole-transcriptome sequencing analysis confirmed the increased expression of PFKFB3 and fatty acid synthetase (FASN) in dedifferentiated VSMCs. More importantly, FASN upregulation was observed in neointimal VSMCs of human stenotic carotid arteries. Finally, interfering with PFKFB3 or FASN suppressed vascular injury-induced mTORC1 activation, VSMC dedifferentiation, and neointima formation. Together, this study demonstrated that PFKFB3-mediated glycolytic reprogramming and FASN-mediated lipid metabolic reprogramming are distinctive features of VSMC phenotypic switching and could be potential therapeutic targets for treating vascular diseases with neointima formation. This article is protected by copyright. All rights reserved.

20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 148-154, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647658

RESUMO

Objective: To primarily explore the efficacy of Zi Huangjing TM preparation in patients with cancer-related fatigue (CRF) during chemotherapy. Methods: This study was designed as a prospective, single-arm, multicenter clinical trial. According to the plan of the study, patients with malignant tumors who had received at least one cycle of chemotherapy and had moderate-to-severe CRF (Piper Fatigue Scale score≥4) were enrolled. All the enrolled patients took Zi Huangjing TM preparation (2.1 g, twice a day) every day during the two subsequent cycles of chemotherapy and were followed up. During the period, the enrolled patients independently completed the Piper Fatigue Scale and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale, and part of their biochemical and immunological indicators were measured at the baseline, before the second cycle of chemotherapy (day 21), and before the third cycle of chemotherapy (day 42). The primary endpoint was the change in Piper Fatigue Scale scores between the baseline and day 42. Results: Eventually, 47 patients completed the entire study. After treatment, the mean score of the Piper Fatigue Scale assessed before the third cycle of chemotherapy (day 42) was 3.21±1.67, which was significantly lower than that at baseline (5.89±1.36) ( P=0.000), and the patients' CRF was significantly improved. In terms of quality of life, the patient's global quality of life, physical functions, role function, emotional function, cognitive function, and social function were significantly improved. In terms of symptom management, the patient's symptoms, such as fatigue, nausea and vomiting, insomnia, and appetite loss also significantly improved. No severe adverse reactions (grades 3 and 4) occurred during the observation period of this study. After evaluation, the adverse reactions that the patients actually had were considered to be related to chemotherapy, but unrelated to Zi Huangjing TM preparation. Conclusion: According to our preliminary investigation, Zi Huangjing TM preparation is safe and has the potential therapeutic effect of improving CRF in cancer patients during chemotherapy. However, further larger-scale randomized controlled clinical studies are needed to confirm the efficacy of Zi Huangjing TM in improving CRF.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Estudos Prospectivos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fadiga/tratamento farmacológico , Fadiga/etiologia
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