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2.
Appl Opt ; 63(8): C1-C7, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568621

RESUMO

Metamaterial filters represent an essential method for researching the miniaturization of infrared spectral detectors. To realize an 8-2 µm long-wave infrared tunable transmission spectral structure, an extraordinary optical transmission metamaterial model was designed based on the grating diffraction effect and surface plasmon polariton resonance theory. The model consisted of an Al grating array in the upper layer and a Ge substrate in the lower layer. We numerically simulated the effects of different structural parameters on the transmission spectra, such as grating height (h), grating width (w), grating distance (d), grating constant (p), and grating length (S 1), by utilizing the finite-difference time-domain method. Finally, we obtained the maximum transmittance of 81.52% in the 8-12 µm band range, with the corresponding structural parameters set to h=50n m, w=300n m, d=300n m, and S 1=48µm, respectively. After Lorentz fitting, a full width at half maximum of 0.94±0.01µm was achieved. In addition, the Ge substrate influence was taken into account for analyzing the model's extraordinary optical transmission performance. In particular, we first realized the continuous tuning performance at the transmission center wavelength (8-12 µm) of long-wave infrared within the substrate tuning thickness (D) range of 1.9-2.9 µm. The structure designed in this paper features tunability, broad spectral bandwidth, and miniaturization, which will provide a reference for the development of miniaturized long-wave infrared spectral filter devices.

3.
Front Pharmacol ; 15: 1333235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572429

RESUMO

Background: Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer's disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly. Methods: In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia. Results: The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells. Conclusion: Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

4.
J Agric Food Chem ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602386

RESUMO

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

5.
Front Pharmacol ; 15: 1359319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584597

RESUMO

The α2-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the α2-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, α2-adrenoceptor mRNA expression was significantly upregulated, and α2-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular-mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25 h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the α2-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.

6.
Sci Adv ; 10(14): eadn1272, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578992

RESUMO

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

7.
Science ; 384(6693): 301-306, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38635711

RESUMO

China's massive wave of urbanization may be threatened by land subsidence. Using a spaceborne synthetic aperture radar interferometry technique, we provided a systematic assessment of land subsidence in all of China's major cities from 2015 to 2022. Of the examined urban lands, 45% are subsiding faster than 3 millimeters per year, and 16% are subsiding faster than 10 millimeters per year, affecting 29 and 7% of the urban population, respectively. The subsidence appears to be associated with a range of factors such as groundwater withdrawal and the weight of buildings. By 2120, 22 to 26% of China's coastal lands will have a relative elevation lower than sea level, hosting 9 to 11% of the coastal population, because of the combined effect of city subsidence and sea-level rise. Our results underscore the necessity of enhancing protective measures to mitigate potential damages from subsidence.

8.
Cancer Cell ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38608702

RESUMO

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis and disrupting the interplay between macrophages and tumor cells attenuates muscle wasting. Collectively, this study identifies a feedforward loop between pancreatic cancer cells and macrophages, underlying the non-autonomous activation of TWEAK secretion from tumor cells thereby providing promising therapeutic targets for pancreatic cancer cachexia.

9.
Heliyon ; 10(6): e27484, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524561

RESUMO

The prevalence and mortality of cardiovascular disease are relatively high. Currently, depression has been proven to be an independent risk factor for the occurrence and poor prognosis of cardiovascular disease. Psycho-cardiovascular comorbidity, as a reciprocal cause and effect, affects each other, leading to the deterioration of clinical prognosis and forming a vicious circle. Coronary artery disease comorbidity with depression is a common disease in psycho-cardiology medicine. This paper expounds on the exploration of the treatment model of psycho-cardiology from the aspects of epidemiological characteristics, comorbidity mechanism, screening, diagnosis, and treatment.

10.
Sci Rep ; 14(1): 6435, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499600

RESUMO

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.


Assuntos
Proteínas Relacionadas à Folistatina , Hiperparatireoidismo , Humanos , Análise da Randomização Mendeliana , Locos de Características Quantitativas/genética , Classe III de Fosfatidilinositol 3-Quinases , Efeitos Psicossociais da Doença , Estudo de Associação Genômica Ampla
11.
Mol Nutr Food Res ; 68(7): e2300739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38528314

RESUMO

Age-related cognitive decline is primarily attributed to the progressive weakening of synaptic function and loss of synapses, while age-related gut microbial dysbiosis is known to impair synaptic plasticity and cognitive behavior by metabolic alterations. To improve the health of the elderly, the protective mechanisms of Oudemansiella raphanipes polysaccharide (ORP-1) against age-related cognitive decline are investigated. The results demonstrate that ORP-1 and its gut microbiota-derived metabolites SCFAs restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by increasing the abundance of beneficial bacteria Dubosiella, Clostridiales, and Prevotellaceae and reducing the abundance of harmful bacteria Desulfovibrio, strengthen intestinal barrier integrity by abolishing age-related alterations of tight junction (TJ) and mucin 2 (MUC2) proteins expression, diminish age-dependent increase in circulating inflammatory factors, ameliorate cognitive decline by reversing memory- and synaptic plasticity-related proteins levels, and restrain hyperactivation of microglia-mediated synapse engulfment and neuroinflammation. These findings expand the understanding of prebiotic-microbiota-host interactions.


Assuntos
Agaricales , Eixo Encéfalo-Intestino , Disfunção Cognitiva , Humanos , Idoso , Disbiose/metabolismo , Prebióticos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/metabolismo
12.
Environ Pollut ; 348: 123828, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522604

RESUMO

Glyphosate (GLY) is a widely used herbicide that has been revealed to inhibit testosterone synthesis in humans and animals. Melatonin (MET) is an endogenous hormone that has been demonstrated to promote mammalian testosterone synthesis via protecting mitochondrial function. However, it remains unclear whether MET targets mitochondria to alleviate GLY-inhibited testosterone synthesis in avian. In this study, an avian model using 7-day-old rooster upon chronic exposure to GLY with the treatment of MET was designed to clarify this issue. Data first showed that GLY-induced testicular Leydig cell damage, structural damage of the seminiferous tubule, and sperm quality decrease were mitigated by MET. Transcriptomic analyses of the testicular tissues revealed the potentially critical role of mitophagy and steroid hormone biosynthesis in the process of MET counteracting GLY-induced testicular damage. Also, validation data demonstrated that the inhibition of testosterone synthesis due to GLY-induced mitochondrial dynamic imbalance and concomitant Parkin-dependent mitophagy activation is alleviated by MET. Moreover, GLY-induced oxidative stress in serum and testicular tissue were significantly reversed by MET. In summary, these findings demonstrate that MET effectively ameliorates GLY-inhibited testosterone synthesis by inhibiting mitophagy activation, which provides a promising remedy for the application of MET as a potential therapeutic agent to antagonize reproductive toxicity induced by GLY and similar contaminants.


Assuntos
60658 , Melatonina , Humanos , Masculino , Animais , Testosterona , Melatonina/farmacologia , Galinhas , Sêmen , Mitocôndrias , Mamíferos
13.
Phytomedicine ; 127: 155440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452691

RESUMO

BACKGROUND: The high metastasis and mortality rates of head and neck squamous cell carcinoma (HNSCC) urgently require new treatment targets and drugs. A steroidal component of ChanSu, telocinobufagin (TBG), was verified to have anti-cancer effects in various tumors, but its activity and mechanism in anti-HNSCC were still unknown. PURPOSE: This study tried to demonstrate the anti-tumor effect of TBG on HNSCC and verify its potential mechanism. METHODS: The effect of TBG on cell proliferation and metastasis were performed and the TBG changed genes were detected by RNA-seq analysis in HNSCC cells. The GSEA and PPI analysis were used to identify the pathways targeted for TBG-regulated genes. Meanwhile, the mechanism of TBG on anti-proliferative and anti-metastasis were investigated in vitro and in vivo. RESULTS: The in vitro and in vivo experiments confirmed that TBG has favorable anti-tumor effects by induced G2/M phase arrest and suppressed metastasis in HNSCC cells. Further RNA-seq analysis demonstrated the genes regulated by TBG were enriched at the G2/M checkpoint and PLK1 signaling pathway. Then, the bioinformatic analysis of clinical data found that high expressed PLK1 were closely associated with poor overall survival in HNSCC patients. Furthermore, PLK1 directly and indirectly modulated G2/M phase and metastasis (by regulated CTCF) in HNSCC cells, simultaneously. TBG significantly inhibited the protein levels of PLK1 in both phosphorylated and non-phosphorylated forms and then, in one way, inactivated PLK1 failed to activate G2/M phase-related proteins (including CDK1, CDC25c, and cyclin B1). In another way, be inhibited PLK1 unable promote the nuclear translocation of CTCF and thus suppressed HNSC cell metastasis. In contrast, the anti-proliferative and anti-metastasis effects of TBG on HNSCC cell were vanished when cells high-expressed PLK1. CONCLUSION: The present study verified that PLK1 mediated TBG induced anti-tumor effect by modulated G2/M phase and metastasis in HNSCC cells.


Assuntos
Bufanolídeos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Linhagem Celular Tumoral
14.
J Neuroeng Rehabil ; 21(1): 37, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504351

RESUMO

BACKGROUND: Children with unilateral cerebral palsy (UCP) are encouraged to participate in the regular school curriculum. However, even when using the less-affected hand for handwriting, children with UCP still experience handwriting difficulties. Visual-motor integration (VMI) is a predictor of handwriting quality. Investigating VMI in children with UCP is important but still lacking. Conventional paper-based VMI assessments is subjective and use all-or-nothing scoring procedures, which may compromise the fidelity of VMI assessments. Moreover, identifying important shapes that are predictive of VMI performance might benefit clinical decision-making because different geometric shapes represent different developmental stepping stones of VMI. Therefore, a new computer-aided measure of VMI (the CAM-VMI) was developed to investigate VMI performance in children with UCP and to identify shapes important for predicting their VMI performance. METHODS: Twenty-eight children with UCP and 28 typically-developing (TD) children were recruited. All participants were instructed to complete the CAM-VMI and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI). The test items of the CAM-VMI consisted of nine simple geometric shapes related to writing readiness. Two scores of the CAM-VMI, namely, Error and Effort, were obtained by image registration technique. The performances on the Beery-VMI and the CAM-VMI of children with UCP and TD children were compared by independent t-test. A series of stepwise regression analyses were used to identify shapes important for predicting VMI performance in children with UCP. RESULTS: Significant group differences were found in both the CAM-VMI and the Beery-VMI results. Furthermore, Error was identified as a significant aspect for predicting VMI performance in children with UCP. Specifically, the square item was the only significant predictor of VMI performance in children with UCP. CONCLUSIONS: This study was a large-scale study that provided direct evidence of impaired VMI in school-aged children with UCP. Even when using the less-affected hand, children with UCP could not copy the geometric shapes as well as TD children did. The copied products of children with UCP demonstrated poor constructional accuracy and inappropriate alignment. Furthermore, the predictive model suggested that the constructional accuracy of a copied square is an important predictor of VMI performance in children with UCP.


Assuntos
Paralisia Cerebral , Desenvolvimento Infantil , Criança , Humanos , Desempenho Psicomotor , Computadores , Mãos
15.
ACS Omega ; 9(8): 8789-8796, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38434829

RESUMO

In this study, we successfully synthesized well-defined polygonal gold microplates for the first time in an aqueous phase using hydroxyethylcellulose (HEC) in the presence of hydrogen peroxide (H2O2). HEC played a pivotal role during the synthesis, acting not only as a biotemplate but also as an in situ reduction site for the nucleation and growth of gold (Au) microplates. H2O2 played a crucial role in accelerating the growth of Au microplates from the Au nucleus. This methodology is ecofriendly and easy to operate and has potential applications in various fields, such as electronics, photonics, and biotechnology.

16.
Huan Jing Ke Xue ; 45(2): 792-801, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471918

RESUMO

The northern plain of Henan in the lower reaches of the Yellow River is an area where the Yellow River is frequently diverted. The shallow groundwater quality in this area is poor, and many types of components have been found to be exceeding the limit value; however, the contribution of various environmental factors to water quality needs to be further quantified. In order to clarify the genesis of water quality of shallow groundwater in the study area, 330 groups of shallow groundwater samples were collected via a regional water quality survey. The evolution of shallow groundwater quality in the Yellow River diversion area of northern Henan was revealed using the principal component-absolute principal component score-multiple linear regression (PCA-APCS-MLR) model. The results showed that the components with a shallow groundwater excess rate greater than 10% in descending order were manganese, iron, total hardness, total dissolved solids, sodium, fluoride, arsenic, chloride ions, sulfate, and ammonium. In particular, the excess rate of manganese reached 76%. The four factors of dissolution enrichment, native origin of soil, redox conditions, and agricultural activities were identified as the main reasons for poor groundwater quality, which accounted for 71.24% of the cumulative interpretation rate of variance. In addition, the recharge from the surface water also influenced the groundwater quality. The effects of dissolution between the water and aquifer matrix and redox condition in the aquifer of the Yellow River dried-riverway like Xinxiang were significantly enhanced, resulting in the increasing concentration of iron, arsenic, total hardness, TDS, and other components in groundwater. Fluoride enrichment was caused by dissolution enrichment, the origin of the soil, and lateral replenishment of the Yellow River. Groundwater with high manganese concentration was widely affected by the soil matrix. Nitrate pollution of the groundwater was caused by the extensive use of chemical fertilizers in agricultural activities in individual areas.

17.
Biomed Pharmacother ; 172: 116270, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364737

RESUMO

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Humanos , Fibrose Pulmonar/tratamento farmacológico , Peroxidação de Lipídeos , Estresse Oxidativo , Células Epiteliais Alveolares , Ferro
18.
World J Gastrointest Surg ; 16(1): 205-214, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38328333

RESUMO

BACKGROUND: Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis. Postoperative adjuvant external radiation therapy (RT) has been shown to effectively prevent recurrence after liver cancer resection. However, there are multiple RT techniques available, and the differential effects of these techniques in preventing postoperative liver cancer recurrence require further investigation. AIM: To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival (OS) and disease-free survival (DFS) and to determine the optimal strategy. METHODS: This study involved network meta-analyses and followed the PRISMA guidelines. The data of qualified studies published before July 10, 2023, were collected from PubMed, Embase, the Web of Science, and the Cochrane Library. We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints. The magnitudes of the effects were determined using risk ratios with 95% confidential intervals. The results were analyzed using R software and STATA software. RESULTS: A total of 12 studies, including 1265 patients with hepatocellular carcinoma (HCC) after liver resection, were included in this study. There was no significant heterogeneity in the direct paired comparisons, and there were no significant differences in the inclusion or exclusion criteria, intervention measures, or outcome indicators, meeting the assumptions of heterogeneity and transitivity. OS analysis revealed that patients who underwent stereotactic body radiotherapy (SBRT) after resection had longer OS than those who underwent intensity modulated radiotherapy (IMRT) or 3-dimensional conformal RT (3D-CRT). DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS. Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT. CONCLUSION: HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT. IMRT, a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT, may be a preferred option.

19.
Cancer Lett ; 585: 216665, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38290657

RESUMO

Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.


Assuntos
Glioblastoma , Glioma , Naftalenos , Piperazinas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Glioma/genética , Glioma/patologia , Fosforilação , Glioblastoma/patologia , Carcinogênese , Transformação Celular Neoplásica , Glucose , Proteínas Serina-Treonina Quinases/metabolismo
20.
Phytochemistry ; 220: 113993, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38266954

RESUMO

Nine previously unreported various types of monoterpenoid indole alkaloids, together with seven known analogues were isolated from the stem barks of Alstonia scholaris through a silica gel free methodology. The structures of 1-9 were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compound 1 is a modified echitamine-type alkaloid with a novel 6/5/5/7/6/6 hetero hexacyclic bridged ring system, and 8 and 9 exist as a zwitterion and trifluoroacetate salt, respectively. The anti-Toxoplasma activity of all isolates on infected Vero cells were evaluated, which revealed that compound 14 at 0.24 µM displayed potent activity. This study expanded the structural diversity of alkaloids of A. scholaris, and presented their potential application in anti-Toxoplasma drug development.


Assuntos
Alstonia , Alcaloides de Triptamina e Secologanina , Toxoplasma , Animais , Chlorocebus aethiops , Alcaloides de Triptamina e Secologanina/farmacologia , Alcaloides de Triptamina e Secologanina/química , Estrutura Molecular , Alstonia/química , Células Vero , Alcaloides Indólicos
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