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1.
Genomics ; 116(3): 110799, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38286348

RESUMO

Malignant gliomas, characterized by pronounced heterogeneity, a complex microenvironment, and a propensity for relapse and drug resistaniguree, pose significant challenges in oncology. This study aimed to investigate the prognostic value of Ligand and Receptor related genes (LRRGs) within the glioma microenvironment. An intersection of 71 ligand-related genes (LRGs) and 2628 receptor-related genes (RRGs) yielded a total of 69 LRRGs. Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic RiskScore model comprising 28 LRRGs was constructed. The model demonstrated robust prognostic value, further validated in the TCGA-GBMLGG dataset. Subsequent analyses included differential gene expression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment (GSEA), and gene set variation (GSVA) within RiskScore groups. Additionally, evaluations of PPI, mRNA-RBP, mRNA-TF, and mRNA-drug interaction networks were conducted. Four hub genes were identified through differential expression analysis of the 28 LRRGs across various GSE datasets. A multivariate Cox prognostic model was constructed for nomogram analysis, gene mutation analysis, and related expression distribution. This study underscores the role of LRRGs in intercellular communication within the glioma microenvironment and identifies four hub genes crucial for prognostic assessment in clinical glioma patients. These findings offer a potential evaluation framework for glioma patients, enhancing our understanding of the disease and informing future therapeutic strategies.

2.
Database (Oxford) ; 20232023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38150626

RESUMO

De novo molecular generation is a promising approach to drug discovery, building novel molecules from the scratch that can bind the target proteins specifically. With the increasing availability of machine learning algorithms and computational power, artificial intelligence (AI) has emerged as a valuable tool for this purpose. Here, we have developed a database of 3D ligands that collects six AI models for de novo molecular generation based on target proteins, including 20 disease-associated targets. Our database currently includes 1767 protein targets and up to 164 107 de novo-designed molecules. The primary goal is to provide an easily accessible and user-friendly molecular database for professionals in the fields of bioinformatics, pharmacology and related areas, enabling them to efficiently screen for potential lead compounds with biological activity. Additionally, our database provides a comprehensive resource for computational scientists to explore and compare different AI models in terms of their performance in generating novel molecules with desirable properties. All the resources and services are publicly accessible at https://cmach.sjtu.edu.cn/drug/. Database URL: https://cmach.sjtu.edu.cn/drug/.


Assuntos
Inteligência Artificial , Proteínas , Algoritmos , Descoberta de Drogas , Bases de Dados Factuais , Desenho de Fármacos
3.
J Ginseng Res ; 47(6): 714-725, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38107393

RESUMO

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3ß (p-GSK3ß), ß-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3ß inhibitor promoted p-GSK3ß and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

5.
Front Psychiatry ; 14: 1219592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492064

RESUMO

Background: Reversible splenial lesion syndrome (RESLES) is a rare neurological condition characterized by temporary abnormalities in the splenium of the corpus callosum, which has been reported in mental disorders. Previous studies on bipolar disorder (BD) primarily focused on aspects such as brain structure and function, neurochemical changes, and genetics. However, there have been no studies reporting the occurrence of this syndrome during hypomanic episodes and its disappearance during the remission phase in bipolar disorder type 2 (BD-II). Case presentation: We present a case report of a 30 years-old female patient with BD-II who exhibited symptoms of RESLES during a hypomanic episode. The patient, with a 12 years psychiatric history, has experienced recurrent depressive episodes initially, with the first hypomanic episode occurring 8 years ago. During this period, this patient made several visits to the outpatient clinic to have her medications adjusted due to repeated suicide attempts. This time, she was admitted to our hospital with a second hypomanic episode due to drug withdrawal during pregnancy. The RESLES was observed on her brain magnetic resonance image, and it was alleviated after treatment with lithium carbonate and quetiapine until achieving remission. Conclusion: We present the first report of identifying RESLES in BD-II with hypomanic episodes, which subsequently disappears during the remission phase. Our case report highlights a potential association between BD and RESLES, emphasizing the need for future studies to explore the underlying mechanisms connecting these two conditions in greater depth.

6.
Int J Numer Method Biomed Eng ; 39(10): e3737, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37269226

RESUMO

Central venous disease (CVD) with stenosis or occlusion is a severe and prevalent complication for chronic hemodialysis (HD) patients, resulting in dialysis access dysfunction. Percutaneous transluminal angioplasty with stent placement (PTS) has become one of the first-line treatments for CVD. In clinical practice, the extra stents would be used if the curative efficacy of a single stent were unsatisfactory. Aiming to evaluate the therapeutic effect of different PTS schemes, computational fluid dynamics (CFD) simulations on four patients were performed to compare the hemodynamic characteristics of real-life HD patients after stent placement. The three-dimensional central vein's models of each patient were built using computational tomography angiography (CTA) images, and idealized models were constructed as contrast. Two inlet velocity modes were imposed to imitate the blood flow rate of healthy and HD patients. The hemodynamic parameters for different patients were investigated, including wall shear stress (WSS), velocity, and helicity. The results showed that the implantation of double stents is able to improve flexibility. When subjected to external force, the double stents have better radial stiffness. This paper evaluated the therapeutic efficacy of stent placement and provided a theoretical basis for CVD intervention in hemodialysis patients.


Assuntos
Doenças Cardiovasculares , Stents , Humanos , Veias , Angioplastia/métodos , Hemodinâmica
7.
J Funct Biomater ; 14(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37367273

RESUMO

Polymeric heart valves (PHVs) are a promising and more affordable alternative to mechanical heart valves (MHVs) and bioprosthetic heart valves (BHVs). Materials with good durability and biocompatibility used for PHVs have always been the research focus in the field of prosthetic heart valves for many years, and leaflet thickness is a major design parameter for PHVs. The study aims to discuss the relationship between material properties and valve thickness, provided that the basic functions of PHVs are qualified. The fluid-structure interaction (FSI) approach was employed to obtain a more reliable solution of the effective orifice area (EOA), regurgitant fraction (RF), and stress and strain distribution of the valves with different thicknesses under three materials: Carbothane PC-3585A, xSIBS and SIBS-CNTs. This study demonstrates that the smaller elastic modulus of Carbothane PC-3585A allowed for a thicker valve (>0.3 mm) to be produced, while for materials with an elastic modulus higher than that of xSIBS (2.8 MPa), a thickness less than 0.2 mm would be a good attempt to meet the RF standard. What is more, when the elastic modulus is higher than 23.9 MPa, the thickness of the PHV is recommended to be 0.l-0.15 mm. Reducing the RF is one of the directions of PHV optimization in the future. Reducing the thickness and improving other design parameters are reliable means to reduce the RF for materials with high and low elastic modulus, respectively.

8.
Front Pharmacol ; 14: 1106423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006998

RESUMO

Background: Lamotrigine may cause severe skin reactions. There is a known interaction between lamotrigine and valproic acid with an increase in lamotrigine levels and lamotrigine toxicity risk. Few cases of severe rash and systemic reactions in bipolar patients using lamotrigine and valproate have been reported. Here, we report a rare case of severe skin rash and lymphadenopathy associated with lamotrigine-valproic acid combination. Case presentation: An 18-year-old female adolescent with bipolar disorder type I was treated with lamotrigine, magnesium valproate, and perospirone for 12 days. After the last dose of lamotrigine, she abruptly developed generalized rash and swollen lymph nodes, which continued to progress over the next 3 days. This finally subsided after stopping valproate and with glucocorticoid treatment. Conclusion: This case suggests that lamotrigine-valproic acid combination may cause not only rash but also lymphadenopathy. Even though the aforementioned reactions appear after the last dose of lamotrigine, it cannot be ruled out as suspicious. We recommend caution during titration of lamotrigine and valproate and early withdrawal of both when signs of hypersensitivity appear.

9.
Polymers (Basel) ; 15(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36771918

RESUMO

With the improvement of protection technology, the damage power of conventional penetrators has become increasingly inferior. Reactive material is a new type of energetic material, which has strong energy release capabilities under high-velocity-impact conditions. In this paper, the reactive materials were put into the penetrator, and its penetration characteristics were studied. First, the penetrator with enhanced lateral effect (PELE) projectile structure with better penetration capability was obtained by numerical simulation. Then, based on the established polytetrafluoroethylene (PTFE)/Al reactive material reaction model, the numerical simulation and experimental research of the PELE projectile with a reactive inner core penetrating the target were carried out. The results show that the simulation results are in good agreement with the experimental results, which verifies the confidence of the numerical simulation. The PELE projectile had a significant increase in power with the use of a truncated conical head and reactive materials. The residual velocity of the truncated cone PELE projectile increases by 8.41-21% over conventional PELE projectiles. Its damage range is 43% higher than that of conventional penetrators. The simulation method and the conclusions obtained in this paper can provide support and reference for further research on reactive materials and on effectively improving the damage power of the penetrator.

10.
Nat Nanotechnol ; 18(4): 357-364, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36702955

RESUMO

The success of the lead halide perovskites in diverse optoelectronics has motivated considerable interest in their fundamental photocarrier dynamics. Here we report the discovery of photocarrier-induced persistent structural polarization and local ferroelectricity in lead halide perovskites. Photoconductance studies of thin-film single-crystal CsPbBr3 at 10 K reveal long-lasting persistent photoconductance with an ultralong photocarrier lifetime beyond 106 s. X-ray diffraction studies reveal that photocarrier-induced structural polarization is present up to a critical freezing temperature. Photocapacitance studies at cryogenic temperatures further demonstrate a systematic local phase transition from linear dielectric to paraelectric and relaxor ferroelectric under increasing illumination. Our theoretical investigations highlight the critical role of photocarrier-phonon coupling and large polaron formation in driving the local relaxor ferroelectric phase transition. Our findings show that this photocarrier-induced persistent structural polarization enables the formation of ferroelectric nanodomains at low temperature, which suppress carrier recombination and offer the possibility of exploring intriguing carrier-phonon interplay and the rich polaron photophysics.

11.
J Vasc Access ; : 11297298221139640, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36540050

RESUMO

OBJECTIVES: To investigate the risk factors and biomechanical mechanisms of in-stent restenosis (ISR) in central venous occlusive disease (CVOD). PATIENTS AND METHODS: This retrospective study consecutively included 77 maintenance hemodialysis (MHD) patients with CVOD who received the first percutaneous transluminal angioplasty with stenting (PTS) due to symptomatic CVOD in a tertiary hospital. The mean age was 59.7 ± 14.0 years, and 51.9% of patients were male. The clinical characteristics, occurrence of ISR and patency rates were recorded. Finite element method was applied to assess the biomechanical properties of stents. RESULTS: Among 77 patients with a mean CVS score of 8.0 ± 2.8, 20.8%, 62.3%, and 16.9% of patients had the main vein of CVOD in the subclavian vein, brachiocephalic vein, and superior vena cava, respectively. A total of 72 (93.5%) patients received successful PTS treatment, for which the stents implanted were mainly Fluency covered stent (48.6%) and SMART bare stent (31.9%). During 15 (10-24)-months of follow-up, ISR occurred in 36.1% of the 72 patients. The primary and assisted primary patency rates at 6, 12, and 18 months were 78%, 56%, 42% and 95%, 90%, 87%, respectively. A prolonged dialysis vintage was an independent risk factor for ISR, yet the stent type or the main vein location was not correlated with ISR. Among three laser-engraving stents, the SMART stent was the best in terms of flexibility, stress, and strain on stents but worst in stress or strain on vessels. The Luminexx stent was the best in radial force and worst in stress or strain on stents. The Vici stent was the best in stress and strain on vessels and worst in radial force and flexibility. CONCLUSIONS: An unsatisfactory comprehensive biomechanical performance from configurations rooted in existing stents may account for the high incidence of ISR in CVOD.

12.
J Funct Biomater ; 13(4)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36412877

RESUMO

Hemodialysis is an important means to maintain life in patients with end-stage renal disease (ESRD). Approximately 76.8% of patients who begin hemodialysis do so through catheters, which play vital roles in the delivery of hemodialysis to patients. During the past decade, the materials, structures, and surface-coating technologies of catheters have constantly been evolving to ameliorate catheter-related problems, such as recirculation, thrombosis, catheter-related infections, and malfunction. In this study, based on the commercial GDK catheter, six catheter models (GDK, GDK1, GDK2, GDK3, GDK4, and GDK5) with different lumen diameters and different geometric features of side holes were established, and computational flow dynamics (CFD) were used to measure flow rate, shear stress, residence time (RT), and platelet lysis index (PLI). These six catheters were then printed with polycarbonate PC using 3D printing technology to verify recirculation rates. The results indicated that: (1) the catheter with a 5.5 mm outer diameter had the smallest average shear stress in the arterial lumen and the smallest proportion of areas with shear stress > 10 pa. With increasing catheter diameter, the shear stress in the tip volume became lower, the average RT increased, and the PLI decreased due to larger changes in shear stress; (2) the catheters with oval-shaped side holes had smaller shear stress levels than those with circular-shaped holes, indicating that the oval design was more effective; (3) the catheter with parallel dual side holes had uniformly distributed flow around side holes and exhibited lower recirculation rates in both forward and reverse connections, while linear multi-side holes had higher shear stress levels due to the large differences in flow around side holes. The selection of the material and the optimization of the side holes of catheters have significant impacts on hemodynamic performances and reduce the probability of thrombosis, thus improving the efficiency of dialysis. This study would provide some guidance for optimizing catheter structures and help toward the commercialization of more efficient HD catheters.

13.
Nat Nanotechnol ; 17(11): 1206-1213, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36266508

RESUMO

The miniaturization of silicon-based electronics has motivated considerable efforts in exploring new electronic materials, including two-dimensional semiconductors and halide perovskites, which are usually too delicate to maintain their intrinsic properties during the harsh device fabrication steps. Here we report a convenient plug-and-probe approach for one-step simultaneous van der Waals integration of high-k dielectrics and contacts to enable top-gated transistors with atomically clean and electronically sharp dielectric and contact interfaces. By applying the plug-and-probe top-gate transistor stacks on two-dimensional semiconductors, we demonstrate an ideal subthreshold swing of 60 mV per decade. Using this approach on delicate lead halide perovskite, we realize a high-k top-gate CsPbBr3 transistor with a low operating voltage and a very high two-terminal field-effect mobility of 32 cm2 V-1 s-1. This approach can be extended to centimetre-scale MoS2 and perovskite and generate top-gated transistor arrays, offering a rapid and convenient way of accessing intrinsic properties of delicate emerging materials.

14.
Front Neurol ; 13: 903648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158945

RESUMO

Background: Blindness and stroke resulting from hyaluronic acid (HA) fillers are not frequently reported complications. Reports on stroke recovery after HA injection are limited. In the current study, the recovery process, task-based functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and neurophysiological changes of a patient with monocular blindness and ipsilateral motor cortical stroke after forehead injection of HA are explored. Case-report: The study comprised a 34-year-old female patient who presented with left eye blindness and a stroke after receiving an HA injection a month before admission. The lesion was mainly limited to the left precentral gyrus, and the patient had pure arm monoparesis. For 3 weeks, the patient received conventional rehabilitation treatments and ten sessions of repetitive transcranial magnetic stimulation (rTMS) intervention. Clinical assessments, neurophysiological evaluation, task-based fMRI, and DTI examinations were conducted to assess her motor improvement and the possible neuro mechanism. Clinical rehabilitation impact: The patient's right upper limb motor function was almost completely restored after receiving rehabilitation therapy. However, the vision in her left eye did not show significant improvement. The neurophysiological evaluation showed partial recovery of the ipsilesional motor evoked potentials (MEPs). DTI results showed that the ipsilesional corticospinal tract (CST) was intact. Task-based fMRI results indicated that the activation pattern of the affected hand movement was gradually restored to normal. Conclusion: A case of good motor recovery after stroke due to HA injection with a lesion mainly restricted to the precentral gyrus but without CST damage is presented in the current study. Further studies should be conducted to explore the efficacy and the mechanisms of rehabilitation and neuromodulation approaches to motor cortical stroke.

15.
Eur J Med Chem ; 240: 114571, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35792385

RESUMO

Inhibition of ß-lactamases is a promising strategy to overcome antimicrobial resistance to commonly used ß-lactam antibiotics. Boronic acid derivatives have proven to be effective inhibitors of ß-lactamases due to their direct interaction with the catalytic site of these enzymes. We synthesized a series of phenylboronic acid derivatives and evaluated their structure-activity relationships as Klebsiella pneumoniae carbapenemase (KPC-2) inhibitors. We identified potent KPC-2 inhibitors 2e & 6c (Ki = 0.032 µM and 0.038 µM, respectively) that enhance the activity of cefotaxime in KPC-2 expressing Escherichia coli. The measured acid dissociation constants (pKa) of selected triazole-containing phenylboronic acids was broad (5.98-10.0), suggesting that this is an additional property of the compounds that could be tuned to optimize the target interaction and/or the physicochemical properties of the compounds. These findings will help to guide the future development of boronic acid compounds as inhibitors of KPC-2 and other target proteins.


Assuntos
Klebsiella pneumoniae , Triazóis , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Ácidos Borônicos/química , Resistência Microbiana a Medicamentos , Escherichia coli , Testes de Sensibilidade Microbiana , Triazóis/farmacologia , Inibidores de beta-Lactamases/metabolismo , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo
16.
Nature ; 606(7916): 902-908, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35768590

RESUMO

The discovery of chiral-induced spin selectivity (CISS) opens up the possibility to manipulate spin orientation without external magnetic fields and enables new spintronic device designs1-4. Although many approaches have been explored for introducing CISS into solid-state materials and devices, the resulting systems so far are often plagued by high inhomogeneity, low spin selectivity or limited stability, and have difficulties in forming robust spintronic devices5-8. Here we report a new class of chiral molecular intercalation superlattices (CMIS) as a robust solid-state chiral material platform for exploring CISS. The CMIS were prepared by intercalating layered two-dimensional atomic crystals (2DACs) (such as TaS2 and TiS2) with selected chiral molecules (such as R-α-methylbenzylamine and S-α-methylbenzylamine). The X-ray diffraction and transmission electron microscopy studies demonstrate highly ordered superlattice structures with alternating crystalline atomic layers and self-assembled chiral molecular layers. Circular dichroism studies show clear chirality-dependent signals between right-handed (R-) and left-handed (S-) CMIS. Furthermore, by using the resulting CMIS as the spin-filtering layer, we create spin-selective tunnelling junctions with a distinct chirality-dependent tunnelling current, achieving a tunnelling magnetoresistance ratio of more than 300 per cent and a spin polarization ratio of more than 60 per cent. With a large family of 2DACs of widely tunable electronic properties and a vast selection of chiral molecules of designable structural motifs, the CMIS define a rich family of artificial chiral materials for investigating the CISS effect and capturing its potential for new spintronic devices.

17.
Front Genet ; 12: 698947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691143

RESUMO

Background: Long non-coding RNAs (lncRNAs) reportedly play important roles in biomarker and tumorigenesis of gastric cancer (GC). This study aimed to determine the potential application of prognostic lncRNA signature and identified the role of LINC01614 in carcinogenesis in GC. Material and Methods: Data accessed from the Cancer Genome Atlas database was used to construct a lncRNA signature. Joint effect analysis of the signature and clinical parameters was performed to verify the clinical value of the signature. Co-expression analysis was conducted for prognostic lncRNAs and protein-coding genes. Moreover, the relative expression of LINC01614 was validated in GC tissues and cell lines. In vitro and in vivo experiments were conducted to analyze the biological functions of the newly identified gene in GC cells. Results: A seven-lncRNA (LINC01614, LINC01537, LINC01210, OVAAL, LINC01446, CYMP-AS1, and SCAT8) signature was identified as a promising prognostic signature in GC. Results indicated that the seven-lncRNA was involved in tumorigenesis and progression pathways. LINC01614 expression was identified and found to be upregulated in GC tissues and cells. The study findings revealed that LINC01614 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Knockdown of LINC01614 arrested cell cycle distribution at the G2/M phase. Further, LINC01614 also promoted tumor growth in vivo. Conclusion: We developed an independent seven-lncRNA biomarker for prognostic prediction and identified LINC01614 as an oncogenic lncRNA in GC.

18.
Eur J Pharmacol ; 910: 174458, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34480884

RESUMO

Abnormal melanogenesis and melanosome transport can cause skin pigmentation disorders that are often treated using ginseng-based formulation. We previously found that phenolic acid compounds in ginseng root could inhibit melanin production and as a skin-whitening agents. However, mechanisms of action underlying effects of ginseng phenolic acid monomers on melanogenesis remain unclear. This study was conducted to investigate effects of salicylic acid, a main ginseng root phenolic acid component, on melanogenesis and melanosome functions in melanocytes of zebrafish and other species. Salicylic acid exhibited no cytotoxicity and reduced melanin levels and tyrosinase activity in B16F10 murine melanoma cells and normal human epidermal melanocytes regardless of prior cell stimulation with α-melanocyte stimulating hormone. Additionally, salicylic acid treatment reduced expression of melanogenic enzymes tyrosinase, tyrosinase-related protein 1 and tyrosinase-related protein 2, while reducing expression of their master transcriptional regulator, microphthalmia-associated transcription factor. Moreover, reduced phosphorylation of cAMP response-element binding protein was observed due to reduced cAMP levels resulting from salicylic acid inhibition of upstream signal regulators (adenylyl cyclase and protein kinase A). Furthermore, salicylic acid treatment suppressed expression of transport complex-associated proteins melanophilin and myosin Va in two UVB-treated melanocytic cell lines, suppressed phagocytosis of fluorescent microspheres by UVB-stimulated human keratinocytes (HaCaT), inhibited protease-activated receptor 2 activation by reducing both Ca2+ release and activation of phosphoinositide 3 kinase/AKT and mitogen-activated protein kinases and induced anti-melanogenic effects in zebrafish. Collectively, these results indicate that salicylic acid within ginseng root can inhibit melanocyte melanogenesis and melanin transport, while also suppressing keratinocyte phagocytic function.


Assuntos
Hiperpigmentação/tratamento farmacológico , Melaninas/metabolismo , Melanossomas/metabolismo , Panax/química , Ácido Salicílico/farmacologia , Animais , Cálcio/metabolismo , Linhagem Celular , AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Oxirredutases Intramoleculares/metabolismo , Queratinócitos/efeitos dos fármacos , Melaninas/antagonistas & inibidores , Melanócitos/efeitos dos fármacos , Melanossomas/efeitos dos fármacos , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/metabolismo , Fagocitose/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Receptor PAR-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Peixe-Zebra , alfa-MSH/farmacologia
19.
Wound Repair Regen ; 29(6): 1006-1016, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34448508

RESUMO

Prolonged skin exposure to ultraviolet radiation can lead to development of several acute and chronic diseases, with UVA exposure considered a primary cause of dermal photodamage. We prepared a wild ginseng adventitious root extract (ARE) that could alleviate UVA irradiation-induced NIH-3T3 cell viability decline. After employing a series of purification methods to isolate main active components of ARE, adventitious root protein mixture (ARP) was identified then tested for protective effects against UVA irradiation-induced NIH-3T3 cell damage. The results showed that ARP treatment significantly reduced UVA-induced cell viability decline and confirmed that the active constituent of ARP was the protein, since proteolytic hydrolysis and heat treatment each eliminated ARP protective activity. Moreover, ARP treatment markedly inhibited UVA-induced apoptosis, cell cycle arrest and DNA fragmentation, while also significantly reversing UVA effects (elevated Bax levels, reduced Bcl-2 expression) by reducing Bax levels and increasing Bcl-2 expression. Mechanistically, ARP promoted Akt phosphorylation regardless of UVA exposure, thus confirming ARP resistance to inactivation by UVA light. Notably, in the presence of Akt inhibitor SC0227, ARP could no longer counteract UVA-induced cell viability decline and DNA fragmentation. Additionally, our results demonstrated that ARP treatment protected UVA-irradiated NIH-3T3 cells by preventing UVA-induced reduction of collagen-I expression. Taken together, these results suggest that ARP treatment of NIH-3T3 cells effectively mitigated UVA-induced cell viability decline by activating intracellular Akt to reduce UVA-induced DNA damage, leading to reduced rates of apoptosis and cell cycle arrest after UVA exposure and restoring collagen expression to normal levels.


Assuntos
Panax , Raios Ultravioleta , Animais , Apoptose , Camundongos , Células NIH 3T3 , Proteínas Proto-Oncogênicas c-akt , Raios Ultravioleta/efeitos adversos , Cicatrização
20.
Materials (Basel) ; 14(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206650

RESUMO

Recent studies have shown that the energy release capacity of Polytetrafluoroethylene (PTFE)/Al with Si, and CuO, respectively, is higher than that of PTFE/Al. PTFE/Al/Si/CuO reactive materials with four proportions of PTFE/Si were designed by the molding-sintering process to study the influence of different PTFE/Si mass ratios on energy release. A drop hammer was selected for igniting the specimens, and the high-speed camera and spectrometer systems were used to record the energy release process and the flame spectrum, respectively. The ignition height of the reactive material was obtained by fitting the relationship between the flame duration and the drop height. It was found that the ignition height of PTFE/Al/Si/CuO containing 20% PTFE/Si is 48.27 cm, which is the lowest compared to the ignition height of other Si/PTFE ratios of PTFE/Al/Si/CuO; the flame temperature was calculated from the flame spectrum. It was found that flame temperature changes little for the same reactive material at different drop heights. Compared with the flame temperature of PTFE/Al/Si/CuO with four mass ratios, it was found that the flame temperature of PTFE/Al/Si/CuO with 20% PTFE/Si is the highest, which is 2589 K. The results show that PTFE/Al/Si/CuO containing 20% PTFE/Si is easier to be ignited and has a stronger temperature destruction effect.

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