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1.
Small ; 20(4): e2305870, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37705123

RESUMEN

All-inorganic cesium lead bromide quantum dots (CsPbBr3 -QD) compounds are potential candidates for optoelectronic devices, because of their excellent fluorescence luminescence and thermal stability. However, the many heterojunction interfaces and large band gap induce the low power conversion efficiency in the CsPbBr3 -QD heterojunction, limiting its practical applications. Hereby, in combination with the pressure regulation and TiO2 /CsPbBr3 -QD heterojunction, the interface interaction within the heterojunction can be enhanced and the band gap can be narrowed. The pressure-induced O─Ti─O bond softening and PbBr6 octahedron stiffening at the interface region significantly enhance the interface interactions that are favorable to the carrier transport. Compared with CsPbBr3 -QD, the atomic interaction between Pb and Br of TiO2 /CsPbBr3 -QD heterojunction can be dramatically enhanced at high pressures, leading to increased band gap narrowing rate by two times, which is useful to widen the absorption spectrum. The fluorescence intensity increases by two times. Compression increases the photocurrent and maintains it after the pressure is released, which is due to the enhanced interface interaction induced by the high pressure. The findings provide new opportunities to adjust the physical properties of perovskite heterogeneous structures, and have important applications in the field of new-generation photovoltaic devices.

2.
BMC Microbiol ; 24(1): 90, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493114

RESUMEN

BACKGROUND: To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice. METHODS: RNA-seq assays and high-throughput sequencing of bacterial 16 S rDNA and fungal internal transcribed spacer (ITS) gene sequences were used to identify differentially expressed host genes and fungal composition profiles in conjunctival tissues of diabetic BKS-db/db mice and BKS (control) mice. Functional enrichment analysis of differentially expressed genes and the correlation between the relative abundance of bacterial and fungal taxa in the intestinal mucosa were also performed. RESULTS: Totally, 449 differential up-regulated genes and 1,006 down-regulated genes were identified in the conjunctival tissues of diabetic mice. The differentially expressed genes were mainly enriched in metabolism-related functions and pathways. A decrease in conjunctival bacterial species diversity and abundance in diabetic mice compared to control mice. In contrast, fungal species richness and diversity were not affected by diabetes. The microbial colonies were mainly associated with cellular process pathways regulating carbohydrate and lipid metabolism, as well as cell growth and death. Additionally, some interactions between bacteria and fungi at different taxonomic levels were also observed. CONCLUSION: The present study revealed significant differences in the abundance and composition of bacterial and fungal communities in the conjunctival tissue of diabetic mice compared to control mice. The study also highlighted interactions between bacteria and fungi at different taxonomic levels. These findings may have implications for the diagnosis and treatment of diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbiota , Animales , Ratones , Hongos/genética , Bacterias/genética , Secuenciación de Nucleótidos de Alto Rendimiento
3.
J Transl Med ; 21(1): 769, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907984

RESUMEN

Cancer is a malignant tumor that seriously threatens human life and health. At present, the main treatment methods include surgical resection, chemotherapy, radiotherapy, and immunotherapy. However, the mechanism of tumor occurrence and development is complex, and it produces resistance to some traditional treatment methods, leading to treatment failure and a high mortality rate for patients. Therefore, exploring the molecular mechanisms of tumor occurrence, development, and drug resistance is a very important task. MiRNAs are a type of non-coding small RNA that regulate a series of biological effects by binding to the 3'-UTR of the target mRNA, degrading the mRNA, or inhibiting its translation. MiR-1-3p is an important member of them, which is abnormally expressed in various tumors and closely related to the occurrence and development of tumors. This article introduces miR-1-3p from multiple aspects, including its production and regulation, role in tumor occurrence and development, clinical significance, role in drug resistance, and approaches for targeting miR-1-3p. Intended to provide readers with a comprehensive understanding of the important role of miR-1-3p in tumors.


Asunto(s)
MicroARNs , Neoplasias , Humanos , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias/genética
4.
Pharmacol Res ; 187: 106555, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36403721

RESUMEN

BACKGROUND: Perineural invasion (PNI) has a high incidence and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Our study aimed to identify the underlying molecular mechanism of PNI and propose effective intervention strategies. METHODS: To observe PNI in vitro and in vivo, a Matrigel/ dorsal root ganglia (DRG) model and a murine sciatic nerve invasion model were respectively used. Magnetic resonance (MR) imaging and positron emission tomography/computed tomography (PET-CT) imaging were also used to evaluate tumor growth. Publicly available datasets and PDAC tissues were used to verify how the nerve cells regulate PDAC cells' PNI. RESULTS: Our results showed that glutamate from nerve cells could cause calcium influx in PDAC cells via the N-methyl-d-aspartate receptor (NMDAR), subsequently activating the downstream Ca2+ dependent protein kinase CaMKII/ERK-MAPK pathway and promoting the mRNA transcription of gene METTL3. Next, METTL3 upregulates the expression of hexokinase 2 (HK2) through N6-methyladenosine (m6A) modification in mRNA, enhances the PDAC cells' glycolysis, and promotes PNI. Furthermore, the IONPs-PEG-scFvCD44v6-scAbNMDAR2B nanoparticles dual targeting CD44 variant isoform 6 (CD44v6) and t NMDAR subunit 2B (NMDAR2B) on PDAC cells were synthesized and verified showing a satisfactory blocking effect on PNI. CONCLUSIONS: Here, we firstly provided evidence that glutamate from the nerve cells could upregulate the expression of HK2 through mRNA m6A modification via NMDAR2B and downstream Ca2+ dependent CaMKII/ERK-MAPK pathway, enhance the glycolysis in PDAC cells, and ultimately promote PNI. In addition, the dual targeting nanoparticles we synthesized were verified to block PNI effectively in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Ratones , Animales , Ácido Glutámico , Hexoquinasa , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Tomografía Computarizada por Tomografía de Emisión de Positrones , Invasividad Neoplásica , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neuronas/metabolismo , Línea Celular Tumoral , Neoplasias Pancreáticas
5.
Nanotechnology ; 34(44)2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37506682

RESUMEN

The application of electrochemical hydrodechlorination has been impeded due to the low utilization and activity of Pd catalyst. Herein, a series of Pd catalysts were prepared via the controllable evolution of Zn state during the pyrolysis of ZIF-8 nanosheet. Various forms of Pd with different chemical surroundings were generated upon the combined use of galvanic displacement and ion exchange process. Electrocatalytic hydrodechlorination of 4-chlorophenol was performed and the electrocatalytic hydrodechlorination efficiency of Pd/CN reaches 100% within 3 h at extra low Pd concentration. The coexistence of zero-valent Pd (Pd0) and nitrogen coordinated Pd (Pd-N) was verified by XAFS which provide multiple active sites for focusing on adsorbing H* and cracking C-Cl respectively. The synergetic effect between different chemical state of Pd for efficient hydrodechlorination of chloroaromatics and scheme for dexterous preparation of Pd based electrocatalyst are proposed and discussed.

6.
Eur J Clin Pharmacol ; 79(5): 663-670, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36976322

RESUMEN

OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.


Asunto(s)
Insuficiencia Cardíaca , Hipotensión , Neprilisina , Humanos , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Combinación de Medicamentos , Pueblos del Este de Asia , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/genética , Hipotensión/inducido químicamente , Hipotensión/genética , Neprilisina/genética , Polimorfismo Genético , Volumen Sistólico , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Valsartán/uso terapéutico
7.
Bioorg Chem ; 137: 106617, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37267793

RESUMEN

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenib/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Relación Estructura-Actividad , Células Hep G2 , Proliferación Celular , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral
8.
Int J Clin Pharmacol Ther ; 61(3): 129-138, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36458443

RESUMEN

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.


Asunto(s)
Pueblos del Este de Asia , Pirazoles , Piridonas , Equivalencia Terapéutica , Humanos , Área Bajo la Curva , Estudios Cruzados , Ayuno , Voluntarios Sanos , Comprimidos , Pirazoles/farmacocinética , Piridonas/farmacocinética
9.
BMC Ophthalmol ; 23(1): 338, 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37507767

RESUMEN

BACKGROUND: To investigate the role of neutrophils in corneal nerve regeneration. METHODS: A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups. RESULTS: Neutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group. CONCLUSION: Neutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.


Asunto(s)
Lesiones de la Cornea , Neutrófilos , Animales , Ratones , Factor de Crecimiento Epidérmico , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Córnea/metabolismo , Regeneración Nerviosa
10.
BMC Ophthalmol ; 23(1): 315, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37438731

RESUMEN

BACKGROUND: To compare vitreous angiomosaic images (VAMIs), obtained by widefield swept-source optical coherence tomographic angiography (wfSS-OCTA) and the image of fluorescein fundus angiography (FFA) in the identification of retinal neovascularization (NV) in patients with diabetic retinopathy (DR). METHODS: In this prospective observational study, severe non-proliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) patients were included. All patients underwent FFA and wfSS-OCTA. The number of NVs identified by wfSS-OCTA VAMIs using five fixations 12 × 12 mm montage scans and the resembling FFA images were compared. RESULTS: Fifty-three eyes of 29 patients were enrolled. NVs were detected in 25 eyes by using FFA, including 9 NVs of the disc (NVDs) and 72 NVs elsewhere (NVEs), and in 29 eyes by OCTA, including 11 NVDs and 90 NVEs. The detection rate of NV and NVD of OCTA was comparable to that of FFA (p > 0.05), and the level of agreement was excellent (κ = 0.850, κ = 0.754). Using FFA as the gold standard, the sensitivity for detection of NV by OCTA was 100.0%, specificity was 85.7%, the positive-predictive value was 86.2%, and the negative-predictive value was 100.0%. Compared with FFA, OCTA was superior in terms of the number of NVEs identified (p = 0.024). When we excluded images of patients treated with anti-vascular endothelial growth factor (VEGF) intravitreal therapy for < 3 months, OCTA was comparable to FFA in terms of the number of NVEs discovered (p = 0.203), with excellent agreement (intraclass correlation coefficient = 0.941). CONCLUSIONS: WfSS-OCTA is an independent non-invasive alternative to FFA for NV discovery, NVD detection, and individual NVE identification, particularly in patients with PDR who have a history of prior treatment with anti-VEGF.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Neovascularización Retiniana , Humanos , Retinopatía Diabética/diagnóstico , Neovascularización Retiniana/diagnóstico , Angiografía con Fluoresceína , Fondo de Ojo , Fluoresceínas
11.
Am J Emerg Med ; 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38155031

RESUMEN

BACKGROUND: Homocysteine (Hcy) is widely recognized as a significant risk factor for cardiovascular and cerebrovascular diseases. However, our research has uncovered a novel perspective, suggesting that elevated levels of Hcy could serve as an indicator for neurological diseases. This article presents a unique case of Subacute Combined Degeneration of the spinal cord(SCD), characterized by high homocysteine levels, yet normal vitamin B12 and imaging results. This discovery could facilitate early detection and ensure timely referral of patients to specialized departments for further treatment.

12.
Angew Chem Int Ed Engl ; 61(28): e202205491, 2022 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-35506663

RESUMEN

The eco-friendly properties enable two-dimensional (2D) Cu-based perovskites as ideal candidates for next-generation optoelectronics, but practical application is limited by low photoelectric conversion efficiency because of poor carrier transport abilities. Here, we report enhanced structural stability of 2D CuBr4 perovskites under compression up to 30 GPa, without obvious volume collapse or structural amorphization, by inserting organic C6 H5 CH2 NH3 (PMA) groups between layers. The band gap value of (PMA)2 CuBr4 can be effectively tuned from 1.8 to 1.47 eV by employing external pressures, leading to a broadened absorption range of 400-800 nm. Notably, we successfully detected photoconductivity of the photoresponse at pressures from 10 to 40 GPa; the maximum value of 5×10-3  S cm-1 is observed at 28 GPa, indicating potential applications for high performance photovoltaic candidates under extreme conditions.

13.
Mol Pharm ; 18(11): 3931-3950, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34582198

RESUMEN

Organoids have complex three-dimensional structures that exhibit functionalities and feature architectures similar to those of in vivo organs and are developed from adult stem cells, embryonic stem cells, and pluripotent stem cells through a self-organization process. Organoids derived from adult epithelial stem cells are the most mature and extensive. In recent years, using organoid culture techniques, researchers have established various adult human tissue-derived epithelial organoids, including intestinal, colon, lung, liver, stomach, breast, and oral mucosal organoids, all of which exhibit strong research and application prospects. Studies have shown that epithelial organoids are mainly applied in drug discovery, personalized drug response testing, disease mechanism research, and regenerative medicine. In this review, we mainly discuss current organoid culture systems and potential applications of this technique with human epithelial tissue.


Asunto(s)
Células Madre Adultas/citología , Técnicas de Cultivo de Célula/métodos , Evaluación Preclínica de Medicamentos/métodos , Células Epiteliales/citología , Organoides , Técnicas de Cultivo de Célula/tendencias , Evaluación Preclínica de Medicamentos/tendencias , Humanos
14.
Exp Appl Acarol ; 83(2): 271-283, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33452939

RESUMEN

Defensins are the most diverse groups of antimicrobial peptides in invertebrate animals. In ticks, defensins show great potential as targets for tick control, and display future prospect for therapeutic drug development. In the present study, a novel defensin-like gene (Ds-defensin) contributing to the antimicrobial and antioxidant capacity of the tick Dermacentor silvarum was characterized. The full-length of the Ds-defensin gene was 382 bp, which displayed tissue-specific expression and was highly abundant in the salivary glands and carcasses of the adults. It encodes a 71-amino acid defensin-like protein, and the protein precursor is characterized by a 22-amino acid signal peptide and a 34-amino acid mature peptide. The peptide displayed potent activity against most of the tested gram-positive bacteria, including Staphylococcus aureus, S. carnosus and Nocardia asteroides, and one tested gram-negative bacterium, Psychrobacter faecalis. Scanning electron microscopy revealed that the cell wall and surface of treated bacteria became rough and gradually formed pores after a 30-min exposure to the Ds-defensin peptide. Additionally, the peptide also showed significant antioxidant capacity. The above results implied that the defensin-like peptide may play an important role in tick defense and the interaction with microorganisms.


Asunto(s)
Antiinfecciosos , Dermacentor , Ixodidae , Secuencia de Aminoácidos , Animales , Antiinfecciosos/farmacología , Antioxidantes , Defensinas/genética , Péptidos , Psychrobacter
15.
Mol Pharm ; 17(9): 3165-3176, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32787278

RESUMEN

Employing a peptide-based nanoscale drug delivery system is an effective strategy to overcome the poor therapeutic outcomes of chemotherapeutic drugs. Here, we developed a self-assembling peptide-drug delivery system comprising a self-assembling anticancer peptide (R-lycosin-I), as revealed in our previous study, and 10-hydroxycamptothecin (HCPT) for cancer therapy. The results showed that peptide-drug conjugates (R-L-HCPT) could assemble into nanospheres of 40-60 nm in water. Compared with free HCPT, R-L-HCPT nanospheres not only inhibited tumor growth but also suppressed pulmonary metastatic nodules on B16-F10 cells in vivo. In summary, these results indicated that the self-assembling R-lycosin-I could provide a promising nanoscale platform for delivering small-molecule drugs. Moreover, our study might provide new opportunities for the development of a new class of functional peptide-drug-conjugated systems based on nanomaterials, which could synergistically enhance anticancer outcomes.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Nanosferas/química , Neoplasias/tratamiento farmacológico , Péptidos/farmacología , Células A549 , Camptotecina/análogos & derivados , Camptotecina/farmacología , Línea Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Melanoma Experimental , Nanoestructuras/química , Bibliotecas de Moléculas Pequeñas/farmacología
16.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1297-1303, 2020 Mar.
Artículo en Zh | MEDLINE | ID: mdl-32281339

RESUMEN

Quorum sensing(QS) is one of the research hotspots in the fields of microbiology and medicine in recent years. Quorum sensing is a cell communication regulatory system, which is used by bacterial flora to pass on information of population density by sensing specific signaling molecules to the environment. The QS system of bacteria can impact biological functions, such as bacterial growth, proliferation, biofilm formation, virulence factor production, antibiotic synthesis, and ultimately adapt the bacteria to environmental changes. At present, more and more active ingredients can regulate quorum sensing have been found in traditional Chinese medicines(TCM). TCM and their active ingredients can promote the growth of beneficial bacteria, inhibit the proliferation of pathogenic bacteria and finally achieve the purpose of treating diseases. It embodies multi-pathway and multi-target characteristics of traditional Chinese medicine. This article first introduces molecular types and regulation mechanisms of quorum sensing signals between bacteria. On this basis, the human health-related bacterial quorum sensing is summarized, and the regulatory effect of TCM on bacterial quorum sensing system is discussed. Finally, it is noted that the material basis and mechanisms of TCM in improving human health through bacterial quorum sensing system are still unclear. Future research hotspots will focus on quorum sensing active substances, quorum sensing key nodes and relevant targets. In a word, this article provides reference for the treatment of relevant diseases.


Asunto(s)
Bacterias/efectos de los fármacos , Medicina Tradicional China , Percepción de Quorum , Humanos
17.
Cancer Cell Int ; 19: 314, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31798343

RESUMEN

BACKGROUND: The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. Abnormal expression of PHF14 has been identified in various cancers and is known to be implicated in the pathogenesis of tumors. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme). METHODS: Tissue microarrays and public databases interrogation were used to explore the relationship between the expression of PHF14 and GBM. Three stable PHF14-silenced cell lines (U251, U87MG and A172) were constructed to assess the biological functions changes of GBM cells in vitro. In addition, tumorigenicity in vivo was also performed using U87MG cell line. To understand the mechanism of action of PHF14, RNA-Seq, qRT-PCR, Western blot, IC50 assay and subsequent pathway analysis were performed. RESULTS: Our results showed that the expression of PHF14 was upregulated in glioma, especially in GBM. Overexpression of PHF14 translated to poor prognosis in glioma patients. In vitro assays revealed that silencing expression of PHF14 in glioma cells inhibited migration, invasiveness and proliferation and promoted cell apoptosis. Animal assay further confirmed that over-expression of PHF14 was a dismal prognostic factor. Analysis based on RNA-Seq suggested a PHF14-dependent regulation of Wnt signaling networks, which was further validated by qRT-PCR, Western blot and IC50 analysis. In addition, the mRNA expression of several key markers of EMT (epithelial-mesenchymal transition) and angiogenesis was found to change upon PHF14 silencing. CONCLUSIONS: Our data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.

18.
Mol Plant Microbe Interact ; 30(9): 739-753, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28598263

RESUMEN

Phenylalanine ammonia lyase (PAL) is important in the biosynthesis of plant secondary metabolites that regulate growth responses. Although its function is well-established in various plants, the functional significance of PAL genes in nodulation is poorly understood. Here, we demonstrate that the Lotus japonicus PAL (LjPAL1) gene is induced by Mesorhizobium loti infection and methyl-jasmonate (Me-JA) treatment in roots. LjPAL1 altered PAL activity, leading to changes in lignin contents and thicknesses of cell walls in roots and nodules of transgenic plants and, hence, to structural changes in roots and nodules. LjPAL1-knockdown plants (LjPAL1i) exhibited increased infection thread and nodule numbers and the induced upregulation of nodulin gene expression after M. loti infection. Conversely, LjPAL1 overexpression delayed the infection process and reduced infection thread and nodule numbers after M. loti inoculation. LjPAL1i plants also exhibited reduced endogenous salicylic acid (SA) accumulation and expression of the SA-dependent marker gene. Their infection phenotype could be partially restored by exogenous SA or Me-JA application. Our data demonstrate that LjPAL1 plays diverse roles in L. japonicus-rhizobium symbiosis, affecting rhizobial infection progress and nodule structure, likely by inducing lignin modification, regulating endogenous SA biosynthesis, and modulating SA signaling.


Asunto(s)
Genes de Plantas , Lotus/genética , Lotus/inmunología , Fenilanina Amoníaco-Liasa/genética , Rhizobium/fisiología , Simbiosis/genética , Acetatos/farmacología , Ciclopentanos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Lignina/metabolismo , Lotus/enzimología , Lotus/microbiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mesorhizobium/efectos de los fármacos , Mesorhizobium/fisiología , Modelos Biológicos , Oxilipinas/farmacología , Fenotipo , Fenilanina Amoníaco-Liasa/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Rhizobium/efectos de los fármacos , Nódulos de las Raíces de las Plantas/efectos de los fármacos , Nódulos de las Raíces de las Plantas/genética , Nódulos de las Raíces de las Plantas/microbiología , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacología , Simbiosis/efectos de los fármacos
19.
J Pediatr ; 179: 192-196.e4, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27640356

RESUMEN

OBJECTIVES: To validate the sensitivity of an isolated red reflex test in detection of ocular abnormalities of the anterior and posterior segments in newborns. STUDY DESIGN: Red reflex test and comprehensive eye examinations including external inspection, pupil examination, hand-held slit lamp examination, and RetCam fundus imaging (Clarity Medical Systems, Pleasanton, California) were performed in 7641 newborns. All results were documented as negative or positive. Sensitivity and specificity of red reflex test were calculated by the use of comprehensive eye examinations as the reference standard. Anterior abnormalities were separated from posterior abnormalities, and the sensitivity of red reflex test for each group was calculated. RESULTS: The proportion of abnormalities that were correctly classified by red reflex test was greater in anterior segment group (sensitivity = 99.6%, 95% CI 97.1%-100%) than in the posterior group (sensitivity = 4.1%, 95% CI 3.3%-5.1%, χ2 = 1521.382, φ = 0.836, P < .001). CONCLUSIONS: The red reflex test was a useful universal screening tool in detection of anterior abnormalities; however, the test has limitations in detection of posterior abnormalities. The generalization of these results to infants and children and observers with varying levels of expertise may need to be established further.


Asunto(s)
Oftalmopatías/diagnóstico , Tamizaje Neonatal/métodos , Examen Físico/métodos , Técnicas de Diagnóstico Oftalmológico , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad
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