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1.
J Theor Biol ; 584: 111794, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38499267

RESUMEN

Tree shape statistics based on peripheral structures have been utilized to study evolutionary mechanisms and inference methods. Partially motivated by a recent study by Pouryahya and Sankoff on modeling the accumulation of subgenomes in the evolution of polyploids, we present the distribution of subtree patterns with four or fewer leaves for the unrooted Proportional to Distinguishable Arrangements (PDA) model. We derive a recursive formula for computing the joint distributions, as well as a Strong Law of Large Numbers and a Central Limit Theorem for the joint distributions. This enables us to confirm several conjectures proposed by Pouryahya and Sankoff, as well as provide some theoretical insights into their observations. Based on their empirical datasets, we demonstrate that the statistical test based on the joint distribution could be more sensitive than those based on one individual subtree pattern to detect the existence of evolutionary forces such as whole genome duplication.


Asunto(s)
Algoritmos , Modelos Genéticos , Filogenia
2.
Nanotechnology ; 35(29)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38593752

RESUMEN

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer.


Asunto(s)
Clorofilidas , Indoles , Melaninas , Melanoma Experimental , Nanopartículas , Polímeros , Porfirinas , Indoles/química , Indoles/farmacología , Polímeros/química , Polímeros/farmacología , Nanopartículas/química , Animales , Ratones , Melanoma Experimental/patología , Melanoma Experimental/terapia , Línea Celular Tumoral , Porfirinas/química , Porfirinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Fototerapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fotoquimioterapia/métodos , Terapia Fototérmica
3.
Gastric Cancer ; 27(3): 484-494, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38441781

RESUMEN

BACKGROUND: In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA. METHODS: In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases. RESULTS: mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively). CONCLUSIONS: dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.


Asunto(s)
Adenocarcinoma , Neoplasias Encefálicas , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Inestabilidad de Microsatélites , Adenocarcinoma/patología , Reparación de la Incompatibilidad de ADN/genética , ARN Mensajero/genética
4.
Pediatr Cardiol ; 45(3): 471-482, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38265483

RESUMEN

Patent ductus arteriosus stenting (PDAS) for ductal-dependent pulmonary blood flow (DDPBF) provides a new paradigm for managing neonates with single ventricles (SV). Currently, sparse data exist regarding outcomes for subsequent palliation. We describe our experience with inter-stage care and stage 2 (S2P) conversion with PDAS in comparison to a prior era of patients who received surgical aorto-pulmonary shunts (APS). Retrospective review of 18 consecutive DDPBF SV patients treated with PDAS between 2016 and 2021 was done and compared with 9 who underwent APS from 2010 to 2016. Patient outcomes and pulmonary artery (PA) growth were analyzed. S2P was completed in all 18 with PDAS with no cardiac arrests and one post-S2P mortality. In the 9 APS patients, there was one cardiac arrest requiring ECMO and one mortality inter-stage. Off cardiopulmonary bypass strategy was utilized in 10/18 in the PDAS and 1/9 in the APS group (p = 0.005) at S2P. Shorter ventilation time, earlier PO feeding, and shorter hospital stay were noted in the PDAS group (p = 0.01, p = 0.006, p = 0.03) (S2P). Median Nakata index increase inter-stage was not significant between the PDAS and APS at 94.1 mm2/m2 versus 71.7 mm2/m2 (p = 0.94). Median change in pulmonary artery symmetry (PAS) was - 0.02 and - 0.24, respectively, which was statistically significant (p = 0.008). Neurodevelopmental outcomes were better in the PDAS group compared to the APS group (p = 0.02). PDAS provides excellent PA growth, inter-stage survival, progression along multistage single-ventricle palliation, and potentially improved neurodevelopmental outcomes. Most patients can be transitioned through 2 stages of palliation without CPB.


Asunto(s)
Conducto Arterioso Permeable , Corazón Univentricular , Recién Nacido , Humanos , Lactante , Circulación Pulmonar , Resultado del Tratamiento , Cuidados Paliativos , Arteria Pulmonar , Stents , Estudios Retrospectivos , Cateterismo Cardíaco/efectos adversos
5.
Pediatr Cardiol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953954

RESUMEN

Ductal stenting (DS) is an alternative to the Blalock-Taussig-Thomas Shunt (BTTS) as initial palliation for congenital heart disease with duct-dependent pulmonary blood flow (DDBPF). We sought to analyze the impact of intended single ventricle (SV) and biventricular (BiV) repair pathways on the outcome of DS and BTTS in infants with DDPBF. A single-center, retrospective comparison of infants with DDPBF who underwent either DS (2012-2022) or BTTS procedures (2013-2017). Primary outcomes included all-cause mortality and risk of unplanned re-intervention. Participants were divided into four groups: 1.SV with DS, 2.SV with BTTS, 3.BiV with DS, and 4.BiV with BTTS. Fifty-one DS (SV 45%) and 86 BTTS (SV 49%) procedures were undertaken. For those who had DS, mortality was lower in the BiV compared to SV patients (BiV: 0/28, versus SV: 4/23, p = 0.04). Compared to BiV DS, BiV BTTS had a higher risk of combined death or unplanned re-intervention (HR 4.28; CI 1.25-14.60; p = 0.02). In SV participants, there was no difference for either primary outcome based on procedure type. DS was associated with shorter intensive care length of stay for SV participants (mean difference 5 days, p = 0.01) and shorter intensive care and hospital stay for BiV participants (mean difference 11 days for both outcomes, p = 0.001). There is a survival benefit for DS in BiV participants compared with DS in SV and BTTS in BiV participants. Ductal stenting is associated with a shorter intensive care and hospital length of stay.

6.
Chem Biodivers ; 21(4): e202302109, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38379209

RESUMEN

The antioxidant activity and the anti-α-amylase and anti-acetylcholinesterase capacities of secondary metabolites from different organs (roots, stems, leaves and flowers) of Tunisian Satureja barceloi were determined. The variation in the distribution of phenolic metabolites among roots, stems, leaves and flowers extracts of S. barceloi with various solvent systems (methanol, ethyl acetate, hexane and distilled water) has not been characterized before. Significant variation of phenolic compounds was observed according to organs rather than to extracting solvents. The analyzed organs show a high level of phenolic compounds although the stems contains the highest total polyphenols (132.53±0.48 mg AGE/g Ex), flavonoids (48.99±0.65 mg RE/g Ex) and flavonols (34.93±0.29 mg QE/g Ex) contents. The phenolic fraction was dominated by sagerinic acid, caffeic acid glucoside and epigallocatechin, detected using HPLC-PDA/ESI-MS. The antioxidant activity of all extracts, evaluated by four in vitro tests, was high and varied significantly according to the type of solvent used and the plant organ. The aqueous extracts of leaves exhibited the greatest inhibitory effect on alpha-amylase while the methanolic extract of leaves and stems revealed the most important acetylcholinesterase inhibitory effect. Hence, S. barceloi extracts could be used as a source of various bioactive molecules in pharmaceutical industry.


Asunto(s)
Antioxidantes , Satureja , Antioxidantes/farmacología , Acetilcolinesterasa , alfa-Amilasas , Extractos Vegetales/farmacología , Solventes , Metanol , Fenoles/farmacología , Flavonoides/farmacología
7.
Arch Pharm (Weinheim) ; 357(6): e2300543, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38412461

RESUMEN

The genus Albizia is one of the richest genera in phenolics besides other classes of secondary metabolites including saponins, terpenes, and alkaloids with promising medicinal applications. In the current study, UHPLC-PDA-ESI-MS/MS-based metabolic profiling of leaves of Albizia lebbeck, Albizia julibrissin, Albizia odoratissima, Albizia procera, Albizia anthelmintica, Albizia guachapele, Albizia myriophylla, Albizia richardiana, and Albizia lucidior resulted in the tentative identification of 64 metabolites, mainly flavonoids, phenolic acids, saponins, and alkaloids. Some metabolites were identified in Albizia for the first time and could be used as species-specific chemotaxonomic markers, including: apigenin 7-O-dihydroferuloyl hexoside isomers, apigenin 7-O-pentosyl hexoside, quercetin 3-O-rutinoside 7-O-deoxyhexoside, quercetin 3,7-di-O-hexoside deoxyhexoside, quercetin 7-O-feruloyl hexoside, methyl myricetin 7-O-deoxyhexoside, kaempferol di-3-O-di-deoxyhexoside-7-O-hexoside, and kaempferol 3-O-neohesperidoside 7-O-hexoside. Comparative untargeted metabolomic analysis was undertaken to discriminate between species and provide a chemotaxonomic clue that can be used together with morphological and genetic analyses for more accurate classification within this genus. Moreover, the in vitro antiplasmodial activity was assessed and correlated to the metabolic profile of selected species. This was followed by a molecular docking study and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction of the identified budmunchiamine alkaloids, revealing promising interactions with the active site of lactate dehydrogenase of Plasmodium falciparum and good pharmacokinetics and pharmacodynamics, which could help in designing novel antimalarial drugs.


Asunto(s)
Albizzia , Antimaláricos , Metabolómica , Extractos Vegetales , Hojas de la Planta , Plasmodium falciparum , Albizzia/química , Antimaláricos/farmacología , Antimaláricos/química , Plasmodium falciparum/efectos de los fármacos , Hojas de la Planta/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Flavonoides/farmacología , Flavonoides/química , Cromatografía Líquida de Alta Presión , Alcaloides/farmacología , Alcaloides/química , Especificidad de la Especie
8.
Ren Fail ; 46(1): 2319327, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38419565

RESUMEN

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of the plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on renal ischemia/reperfusion (RI/R) injury and explore the underlying mechanisms. RI/R or OGD/R models were established in mice and HK-2 cells, respectively. In vivo, vector or POP-NPs were administered (10 nmol, IV) 48 h after RI/R treatment. In the RI/R mouse model, the OIP5-AS1 and Nrf2/HO-1 expressions were down-regulated, while miR-410-3p expression was upregulated. POP-NPs treatment effectively reversed RI/R-induced renal tissue injury, restoring altered levels of blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, as well as the suppressed expression of SOD and Nrf2/HO-1 in the model mice. Similar results were obtained in cell models treated with POP-NPs. Additionally, miR-410-3p mimics could reverse the effects of POP-NPs on cellular models, partially counteracted by Nrf2 agonists. The binding relationship between OIP5-AS1 and miR-410-3p, alongside miR-410-3p and Nrf2, has been substantiated by dual-luciferase reporter and RNA pull-down assays. The study revealed that POP-NPs can attenuate RI/R-induced injury through miR-410-3p/Nrf2 axis. These findings lay the groundwork for future targeted therapeutic approaches utilizing nanoparticles for RI/R-induced AKI.


Asunto(s)
Lesión Renal Aguda , MicroARNs , Nanopartículas , ARN Largo no Codificante , Daño por Reperfusión , Animales , Ratones , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor 2 Relacionado con NF-E2/genética , Daño por Reperfusión/genética , Lesión Renal Aguda/genética , Lesión Renal Aguda/terapia
9.
Phytochem Anal ; 35(1): 163-183, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37709551

RESUMEN

INTRODUCTION: Cannabis sativa L. is attracting worldwide attention due to various health-promoting effects. Extraction solvent type is critical for the recovery of bioactive compounds from the plant, especially cannabinoids. However, the choice of solvent is varied and not adequately warranted elsewhere, causing confusion in involved fields. OBJECTIVE: The present work aimed to investigate the effect of extraction solvent on C. sativa (hemp) with regard to cannabinoid recovery and phytochemical profile of the extracts, considering most of the related solvents. METHODOLOGY: The majority of solvents reported for C. sativa (n = 14) were compared using a representative hemp pool. Quantitative results for major and minor cannabinoids were rapidly and reliably obtained using ultrahigh-performance liquid chromatography coupled with photodiode array detection (UPLC-PDA). In parallel, high-performance thin-layer chromatographic (HPTLC) fingerprinting was employed, involving less toxic mobile phase than in relevant reports. Various derivatisation schemes were applied for more comprehensive comparison of extracts. RESULTS: Differential selectivity towards cannabinoids was observed among solvents. MeOH was found particularly efficient for most cannabinoids, in addition to solvent systems such as n-Hex/EtOH 70:30 and ACN/EtOH 80:20, while EtOH was generally inferior. For tetrahydrocannabinol (THC)-type compounds, EtOAc and n-Hex/EtOAc 60:40 outperformed n-Hex, despite its use in the official EU method. Solvents that tend to extract more lipids or more polar compounds were revealed based on HPTLC results. CONCLUSION: Combining the observations from UPLC quantitation and HPTLC fingerprinting, this work allowed comprehensive evaluation of extraction solvents, in view of robust quality assessment and maximised utilisation of C. sativa.


Asunto(s)
Cannabinoides , Cannabis , Cannabinoides/análisis , Cannabis/química , Solventes , Cromatografía Líquida de Alta Presión/métodos , Fitoquímicos/análisis , Extractos Vegetales/química
10.
Phytochem Anal ; 35(5): 927-989, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38837522

RESUMEN

INTRODUCTION: Organic molecules that bind to cannabinoid receptors are known as cannabinoids. These molecules possess pharmacological properties similar to those produced by Cannabis sativa L. High-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC, also known as ultra-high-performance liquid chromatography, UHPLC) have become the most widely used analytical tools for detection and quantification of phytocannabinoids in various matrices. HPLC and UPLC (or UHPLC) are usually coupled to an ultraviolet (UV), photodiode array (PDA), or mass spectrometric (MS) detector. OBJECTIVE: To critically appraise the literature on the application of HPLC and UPLC (or UHPLC) methods for the analysis of phytocannabinoids published from January 2020 to December 2023. METHODOLOGY: An extensive literature search was conducted using Web of Science, PubMed, and Google Scholar and published materials including relevant books. In various combinations, using cannabinoid in all combinations, cannabis, hemp, hashish, C. sativa, marijuana, analysis, HPLC, UHPLC, UPLC, and quantitative, qualitative, and quality control were used as the keywords for the literature search. RESULTS: Several HPLC- and UPLC (or UHPLC)-based methods for the analysis of phytocannabinoids were reported. While simple HPLC-UV or HPLC-PDA-based methods were common, the use of HPLC-MS, HPLC-MS/MS, UPLC (or UHPLC)-PDA, UPLC (or UHPLC)-MS, and UPLC (or UHPLC)-MS/MS was also reported. Applications of mathematical and computational models for optimization of protocols were noted. Pre-analyses included various environmentally friendly extraction protocols. CONCLUSION: During the last 4 years, HPLC and UPLC (or UHPLC) remained the main analytical tools for phytocannabinoid analysis in different matrices.


Asunto(s)
Cannabinoides , Cromatografía Líquida de Alta Presión/métodos , Cannabinoides/análisis , Cannabis/química
11.
Phytochem Anal ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741027

RESUMEN

INTRODUCTION: Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. OBJECTIVES: This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α-amylase. METHODOLOGY: An online analysis platform was established and optimized using an ultra-performance liquid chromatography-photo-diode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MS-α-amylase-FLD) system to screen α-amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α-amylase and active compounds were evaluated, which strongly supported the experimental results. RESULTS: Seventy-eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α-amylase binding activity. CONCLUSION: This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.

12.
Nano Lett ; 23(7): 2854-2861, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-36930741

RESUMEN

Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and time-consuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)-mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.


Asunto(s)
Técnicas Biosensibles , Humanos , Inmunoensayo , Límite de Detección , Escherichia coli , Preparaciones de Acción Retardada
13.
Int J Mol Sci ; 25(9)2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38732243

RESUMEN

This study presents the functionalization of silk fabric with SWCNT ink. The first step was the formation of a polydopamine (PDA) thin coating on the silk fabric to allow for effective bonding of SWCNTs. PDA formation was carried out directly on the fabric by means of polymerization of dopamine in alkali conditions. The Silk/PDA fabric was functionalized with SWCNT ink of different SWCNT concentrations by using the dip-coating method. IR and Raman analyses show that the dominant ß-sheet structure of silk fibroin after the functionalization process remains unchanged. The heat resistance is even slightly improved. The hydrophobic silk fabric becomes hydrophilic after functionalization due to the influence of PDA and the surfactant in SWCNT ink. The ink significantly changes the electrical properties of the silk fabric, from insulating to conductive. The volume resistance changes by nine orders of magnitude, from 2.4 × 1012 Ω to 2.3 × 103 Ω for 0.12 wt.% of SWCNTs. The surface resistance changes by seven orders of magnitude, from 2.1 × 1012 Ω to 2.4 × 105 Ω for 0.17 wt.% of SWCNTs. The volume and surface resistance thresholds are determined to be about 0.05 wt.% and 0.06 wt.%, respectively. The low value of the percolation threshold indicates efficient functionalization, with high-quality ink facilitating the formation of percolation paths through SWCNTs and the influence of the PDA linker.


Asunto(s)
Conductividad Eléctrica , Indoles , Tinta , Nanotubos de Carbono , Polímeros , Seda , Indoles/química , Polímeros/química , Seda/química , Nanotubos de Carbono/química , Textiles , Interacciones Hidrofóbicas e Hidrofílicas
14.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38928326

RESUMEN

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatitis , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Pancreatitis/metabolismo , Pancreatitis/genética , Pancreatitis/patología , Pancreatitis/diagnóstico , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Pronóstico , Regulación Neoplásica de la Expresión Génica , Modelos Animales de Enfermedad , Línea Celular Tumoral , Progresión de la Enfermedad
15.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38473837

RESUMEN

As part of the development and production of pharmaceuticals, the purity of Active Pharmaceutical Ingredients stands as a fundamental parameter that significantly influences the quality, safety, and efficacy of the final drug product. Impurities in Active Pharmaceutical Ingredients are various unwanted substances that can appear during the whole manufacturing process, from raw materials to the final product. These impurities can stem from multiple sources, including starting materials, intermediates, reagents, solvents, and even degradation products resulting from exposure to environmental factors such as heat, light, or moisture. Their presence can potentially compromise the therapeutic effect of the drug, introduce unexpected side effects, or even pose safety risks to patients. This study aims to conduct the forced degradation of linagliptin and subsequently attempt to identify the resulting degradants. The degradation procedures were carried out in accordance with the guidelines of the International Committee for Harmonization. The degradation profile of linagliptin was investigated under various conditions, including acid hydrolysis, alkaline hydrolysis, oxidation, heat, and light exposure, utilizing ultra-performance liquid chromatography connected to a photo array detector. Identification and characterization of the degradation products were achieved using an ultra-performance liquid chromatography coupled with a single quadrupole detector mass spectrometer and also a liquid chromatography coupled with a high-resolution mass spectrometry. The identified degradation products demonstrate that linagliptin is particularly susceptible to degradation when exposed to acid and peroxide. Whereas, no significant degradation effects were observed under alkali, thermolytic, and photolytic conditions.


Asunto(s)
Linagliptina , Humanos , Espectrometría de Masas , Cromatografía Liquida/métodos , Oxidación-Reducción , Hidrólisis , Cromatografía Líquida de Alta Presión/métodos , Estabilidad de Medicamentos
16.
Molecules ; 29(3)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38338449

RESUMEN

Radix Rehmanniae (RR), a famous traditional Chinese medicine (TCM) widely employed in nourishing Yin and invigorating the kidney, has three common processing forms in clinical practice, including fresh Radix Rehmanniae (FRR), raw Radix Rehmanniae (RRR), and processed Radix Rehmanniae (PRR). However, until now, there has been less exploration of the dynamic variations in the characteristic constituents and degradation products of catalpol as a representative iridoid glycoside with the highest content in RR during the process from FRR to PRR. In this study, an ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was successfully established for the simultaneous determination of ten characteristic components to explore their dynamic variations in different processed products of RR. Among them, iridoid glycosides, especially catalpol, exhibited a sharp decrease from RRR to PRR. Then, three degradation products of catalpol were detected under simulated processing conditions (100 °C, pH 4.8 acetate buffer solution), which were isolated and identified as jiofuraldehyde, cataldehyde, and norviburtinal, respectively. Cataldehyde was first reported as a new compound. Moreover, the specificity of norviburtinal in self-made PRR samples was discovered and validated, which was further confirmed by testing in commercially available PRR samples. In conclusion, our study revealed the decrease in iridoid glycosides and the production of new degradation substances during the process from FRR to PRR, which is critical for unveiling the processing mechanism of RR.


Asunto(s)
Medicamentos Herbarios Chinos , Extractos Vegetales , Rehmannia , Terpenos , Glucósidos Iridoides , Rehmannia/química , Glicósidos Iridoides/química , Medicamentos Herbarios Chinos/química
17.
Molecules ; 29(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38611740

RESUMEN

It is urgent to develop a polyamide (PA) thin-film composite (TFC) membrane with a new method in this study by designing and constructing a new nanomaterial support layer instead of the conventional support layer. Polydopamine-wrapped single-walled carbon nanotubes (PDA@MWCNTs) as the place of the polymerization reaction can optimize the PA film structure and performance. The resulting composite membrane presents a higher water flux of 15.8 L·m-2·h-1·bar-1 and a rejection rate of 97% to Na2SO4, simultaneously maintaining this high separation performance in 300 min. It is a new ideal to construct novel support layer by using inorganic nanoparticles and organic polymer nanofiber membranes.

18.
Molecules ; 29(5)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38474556

RESUMEN

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.


Asunto(s)
Hipertermia Inducida , Indoles , Nanopartículas , Neoplasias Ováricas , Polímeros , Quercetina/análogos & derivados , Humanos , Femenino , Fototerapia/métodos , Hipertermia Inducida/métodos , Neoplasias Ováricas/tratamiento farmacológico , Doxorrubicina/farmacología
19.
Molecules ; 29(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38893365

RESUMEN

The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.


Asunto(s)
Microextracción en Fase Líquida , Zolpidem , Zolpidem/sangre , Humanos , Microextracción en Fase Líquida/métodos , Cromatografía Líquida de Alta Presión/métodos , Sonicación/métodos , Reproducibilidad de los Resultados , Hipnóticos y Sedantes/sangre , Límite de Detección , Piridinas/sangre
20.
Molecules ; 29(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474683

RESUMEN

Bopyeo-tang (BPT) is composed of six medicinal herbs (Morus alba L., Rehmannia glutinosa (Gaertn.) DC., Panax ginseng C.A.Mey., Aster tataricus L.f., Astragalus propinquus Schischkin, and Schisandra chinensis (Turcz.) Baill.) and has been used for the treatment of lung diseases. This study focused on establishing an analytical method that can simultaneously quantify nine target compounds (i.e., hydroxymethylfurfural, mulberroside A, chlorogenic acid, calycosin-7-O-glucoside, 3,5-dicaffeoylquinic acid, quercetin, kaempferol, schizandrin, and gomisin A) from a BPT sample using high-performance liquid chromatography with a photodiode array detector (HPLC-PDA) and ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). The separation of compounds in both analyses was performed on a C18 reversed-phase column using the gradient elution of water-acetonitrile as the mobile phase. In particular, the multiple reaction monitoring mode was applied for quick and accurate detection in UPLC-MS/MS analysis. As a result of analyzing the two methods, HPLC-PDA and UPLC-MS/MS, the coefficient of determination of the regression equation for each compound was ≥0.9952, and recovery was 85.99-106.40% (relative standard deviation (RSD) < 9.58%). Precision testing of the nine compounds was verified (RSD < 10.0%). The application of these analytical assays under optimized conditions for quantitative analysis of the BPT sample gave 0.01-4.70 mg/g. Therefore, these two assays could be used successfully to gather basic data for clinical research and the quality control of BPT.


Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , República de Corea
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