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1.
Int J Med Sci ; 21(13): 2613-2622, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39439455

RESUMEN

NLRC3, a negative regulator, exhibits considerable potential in the realm of lung cancer immunotherapy by virtue of its profound impact on the immune response intensity, primarily through its regulatory effects on the cGAS-STING pathway. The inhibition of NLRC3 has been found to augment the activity of the aforementioned pathway, thereby enhancing the anti-tumor immune response. This comprehensive review endeavors to elucidate the molecular and genetic structures of NLRC3, its role within the immune system, and its interaction with the cGAS-STING pathway, with a particular emphasis on its potential applications in lung cancer immunotherapy. Existing research underscores NLRC3's capacity to mitigate excessive immune responses via the negative regulation of the cGAS-STING pathway, thus underscoring its significant regulatory role in lung cancer immunotherapy. The development of pharmaceutical interventions and gene therapy strategies targeting NLRC3 presents a promising avenue for the creation of novel therapeutic options for individuals afflicted with lung cancer. Nonetheless, the clinical application of these therapies is confronted with both technical and biological challenges. This review aims to provide a theoretical foundation for related research endeavors and delineate future research directions in this field.


Asunto(s)
Inmunoterapia , Neoplasias Pulmonares , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Humanos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Inmunoterapia/métodos , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Transducción de Señal/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/inmunología , Animales , Péptidos y Proteínas de Señalización Intercelular
3.
Environ Toxicol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041630

RESUMEN

Asparagus officinalis (ASP) has antioxidation, anti-inflammatory, antiaging, and immune system-enhancing effects. We explored the preventive and therapeutic consequences of ASP on the brain damage elicited by fluorosis through network pharmacology and in vivo experimental validation. We ascertained the pharmaceutically active ingredients and drug targets of ASP from the Traditional Chinese Medicine Systems Pharmacology database, predicted the disease targets of fluorosis-induced brain injury using GeneCards and Online Mendelian Inheritance in Man databases, obtained target protein-protein interaction networks in the Search Tool for the Retrieval of Interacting Genes/Proteins database, used Cytoscape to obtain key targets and active ingredients, and conducted enrichment analyses of key targets in the Database for Annotation, Visualization and Integrated Discovery. Enrichment analyses showed that "mitogen-activated protein kinase" (MAPK), "phosphoinositide 3-kinase/protein kinase B" (PI3K-Akt), "nuclear factor-kappa B" (NF-κB), and the "neurotrophin signaling pathway" were the most enriched biological processes and signaling pathways. ASP could alleviate fluorosis-based injury, improve brain-tissue damage, increase urinary fluoride content, and improve oxidation levels and inflammatory-factor levels in the body. ASP could also reduce dental fluorosis, bone damage, fluoride concentrations in blood and bone, and accumulation of lipid peroxide. Upon ASP treatment, expression of silent information regulator (SIRT)1, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), MAPK, NF-κB, PI3K, Akt, and B-cell lymphoma-2 in rat brain tissue increased gradually, whereas that of Bax, caspase-3, and p53 decreased gradually. We demonstrated that ASP could regulate the brain damage caused by fluorosis through the SIRT1/BDNF/TrkB signaling pathway, and reported the possible part played by ASP in preventing and treating fluorosis.

4.
Front Plant Sci ; 15: 1418480, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988635

RESUMEN

Quisqualis fructus (QF) is a traditional Chinese medicine (TCM) that it has a long history in the therapeutic field of killing parasites, eliminating accumulation, and stopping diarrhea. However, the therapeutic material basis of QF is remaining ambiguous nowadays. The geographical origin differences of QF are also usually ignored in the process of medication. In this study, the alcohol-aqueous soluble constituents in QF from different origins were systematically characterized and accurately measured by ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography (HPLC) respectively. Chemometric analysis was performed for origin differentiation and screening of potential quality marker (Q-marker). Finally, A total of 106 constituents were tentatively characterized in positive and negative ion modes, including 29 fatty acids, 26 organic acids, 11 amino acids and derivatives, 10 glycosides, 9 alkaloids and derivatives, and 21 other constituents. QF from different origins were effectively distinguished and 16 constituents were selected as the potential Q-markers subsequently. Four representative components (trigonelline, adenosine, ellagic acid, and 3,3'-di-O-methylellagic acid) in QF samples were simultaneously determined. HPLC fingerprint analysis indicated that the similarity between 16 batches of QF was in the range of 0.870-0.999. The above results provide some insights for the research on the pharmacodynamic constituents, quality control, and geographical discrimination of QF.

5.
Foods ; 13(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38890873

RESUMEN

This study aims to establish a rapid and convenient microwave-assisted digestion method for sample pretreatment to determine amino acid profiles in natural products. This method was applied to analyze the amino acid profiles of Quisqualis Fructus (QF) from different planted origins. The microwave-assisted digestion conditions were optimized by a response surface methodology (RSM), and 17 amino acids in different planted origins of QF were determined by an automatic amino acid analyzer according to the optimized digestion conditions. The contents of 17 amino acids in QF from different planted origins were further analyzed by fingerprint and chemometric analysis. The temperature of microwave digestion at 167 °C, time of microwave digestion at 24 min, and a solid-liquid ratio of 46.5 g/mL was selected as the optimal digestion conditions. The total content of 17 amino acids in QF from different planted origins ranged from 71.88 to 91.03 mg/g. Amino acid composition and nutritional evaluation indicated that the content of medicinal amino acids was higher than aromatic amino acids. The results of fingerprint analysis reflected that the similarity between the 16 batches of QF ranged from 0.889 to 0.999, while chemometrics analysis indicated amino acid content in QF varied from different planted origins, and six important differential amino acids were screened. Compared with the traditional extraction method, microwave-assisted digestion with response surface optimized has the advantages of rapidity, convenience, and reliability, which could be used to study the amino acid profiles in natural products. The amino acid profile of QF indicated that it has a rich medicinal nutritional value. Different planted origins of QF have a high degree of similarity and could be effectively distinguished by chemometric analysis.

6.
Biol Trace Elem Res ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926229

RESUMEN

Lianhua Qingwen capsule (LHQWC) is composed of 13 traditional Chinese herbs. In this study, we employed inductively coupled plasma mass spectrometry (ICP-MS) to quantify the concentrations of 26 inorganic elements (Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Ag, Cd, Cs, Ba, Hg, Tl, Pb, U) across 22 batches of LHQWC. These results were complemented with Chemometrics analysis and health risk assessment of selected hazardous elements. Chemometric analysis revealed significant quality variations among the 22 batches of LHQWC, identifying U, Cs, Tl, Rb, Mn, As, Mg, and Al as characteristic elements influencing formulation consistency. Moreover, the health risk assessment indicated that while levels of Cu, As, Cd, Pb, Cr, and Hg in LHQWC were within acceptable limits, concerns arose regarding vanadium levels in certain batches. These findings underscore the necessity of comprehensive elemental analysis and health risk assessment to ensure the safety and quality of LHQWC. Our study provides valuable insights for both quality evaluation and regulatory considerations in the production of LHQWC and similar herbal formulations.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38847145

RESUMEN

BACKGROUND: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. METHODS: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. RESULTS: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. CONCLUSION: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.


Asunto(s)
Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Ratas Sprague-Dawley , Transducción de Señal , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Trasplante de Células Madre Mesenquimatosas/métodos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/prevención & control , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hemo Oxigenasa (Desciclizante)/metabolismo , Terapia Combinada/métodos , Células Cultivadas
8.
J Org Chem ; 89(9): 6149-6158, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38635972

RESUMEN

The detailed mechanism of transition metal-free-catalyzed monomethylation of 2-naphthyl acetonitrile (1a) with CO2 in the presence of triazabicyclodecene (TBD) and BH3NMe3 was investigated using density functional theory. The C-methylation process proved to generate formaldehyde followed by the formation of the product via an alcohol rather than a methoxyborane intermediate. During the reaction, CO2 is activated to form the TBD-CO2 adduct and BH3NMe3 is changed into TBD-BH2 (IM2) in the presence of TBD. IM2 plays a real reducing role within the system due to the unique coordination capability of the B atom. In addition to enhancing the nucleophilicity of 1a through deprotonation by tBuOK, our research also indicates that the generated tBuOH not only assists in proton transfer to generate an alcohol intermediate but also promotes the regeneration of TBD.

9.
J Transl Med ; 22(1): 272, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475878

RESUMEN

BACKGROUND: In HBV-associated HCC, T cells often exhibit a state of functional exhaustion, which prevents the immune response from rejecting the tumor and allows HCC to progress. Moreover, polymerase-specific T cells exhibit more severe T-cell exhaustion compared to core-specific T cells. However, whether HBV DNA polymerase drives HBV-specific CD8+ T cell exhaustion in HBV-related HCC remains unclear. METHODS: We constructed a Huh7 cell line stably expressing HA-HBV-DNA-Pol and applied co-culture systems to clarify its effect on immune cell function. We also examined how HBV-DNA-Pol modulated PD-L1 expression in HCC cells. In addition, HBV-DNA-Pol transgenic mice were used to elucidate the underlying mechanism of HBV-DNA-Pol/PD-L1 axis-induced T cell exhaustion. RESULTS: Biochemical analysis showed that Huh7 cells overexpressing HBV-DNA-Pol inhibited the proliferation, activation, and cytokine secretion of Jurkat cells and that this effect was dependent on their direct contact. A similar inhibitory effect was observed in an HCC mouse model. PD-L1 was brought to our attention during screening. Our results showed that the overexpression of HBV-DNA-Pol upregulated PD-L1 mRNA and protein expression. PD-L1 antibody blockade reversed the inhibitory effect of Huh7 cells overexpressing HBV-DNA-Pol on Jurkat cells. Mechanistically, HBV-DNA-Pol interacts with PARP1, thereby inhibiting the nuclear translocation of PARP1 and further upregulating PD-L1 expression. CONCLUSIONS: Our findings suggest that HBV-DNA-Pol can act as a regulator of PD-L1 in HCC, thereby directing anti-cancer immune evasion, which further provides a new idea for the clinical treatment of liver cancer.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Virus de la Hepatitis B/genética , ADN Viral , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , ADN Polimerasa Dirigida por ADN/metabolismo
10.
Micromachines (Basel) ; 15(3)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542646

RESUMEN

The power capacity of reflectarray antennas (RAs) is investigated through full-wave simulations and high-power microwave (HPM) experiments in this paper. In order to illustrate the results in detail, two RA elements are designed. The simulated power handling capacity of two RA elements are 7.17 MW/m2 and 2.3 GW/m2, respectively. To further study the HPM RA, two RA prototypes operating at 2.8 GHz are constructed with the aperture size of 1 m × 1 m. Simulations and experimental measurements are conducted for the two prototypes. The experimental results demonstrate that, even when subjected to 1 GW of power, the radiation beam of the RA with the second elements can still propagate in the intended direction. This research will establish a basis for advancing the practicality of RAs in HPM applications.

11.
J Control Release ; 365: 876-888, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38030082

RESUMEN

As one of the most challenging cancers, glioma still lacks efficient therapeutic treatment in clinics. The dilemmas of nanodrug-based therapies for glioma are due not only the limited permeability of the blood-brain barrier (BBB) but also the deficiency of targeting tumor lesions. Thus, spatiotemporally sequential delivery of therapeutics from BBB-crossing to glioma accumulation is considered a strategy to obtain better outcomes. Here, we developed a biomimetic chemotherapy nanodrug composed of the hybrid membrane envelope of U87 cell membranes and RAW264.7 cell membranes, and the core of paclitaxel (PTX)-loaded liposome (PTX@C-MMCL). In the research, PTX@C-MMCL showed superior ability to cross the BBB via RAW264.7 cell membranes and accurate targeting to the brain tumor lesions relying on the homotypic targeting capacity of U87 cell membranes. Furthermore, PTX@C-MMCL can maintain a prolonged circulation in vivo. Importantly, PTX@C-MMCL effectively inhibited the development of glioma. Conclusively, our biomimetic nanodrug holds great potential for brain tumor targeting therapy.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Liposomas/metabolismo , Biomimética , Línea Celular Tumoral , Glioma/metabolismo , Neoplasias Encefálicas/metabolismo , Paclitaxel , Sistemas de Liberación de Medicamentos , Barrera Hematoencefálica/metabolismo
12.
Environ Geochem Health ; 45(12): 9925-9940, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37906380

RESUMEN

This study analyzed the effect of China's fluorosis prevention and control program, which has been in effect for more than 40 years, and the impact of fluorosis on children's health. Relevant research studies were retrieved from the following online databases from the time of their inception to May 2022: PubMed, ScienceDirect, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang. The Review Manager 5.3 software was used in statistical analyses. This article included seventy studies: Thirty-eight studies reported the effect of improving water quality and reducing fluoride content, the incidence rate of dental fluorosis in children, and the level of urinary fluoride, and thirty-two studies reported the intelligence quotient (IQ) and health status of children. Following water improvement strategies, the fluoride levels in drinking water decreased significantly; urinary fluoride levels and dental fluorosis decreased significantly in children. With regard to the effect of fluorosis on the IQ of children, the results showed that the IQ of children in areas with a high fluoride of fluorosis was lesser than that in areas with a low fluoride, and this difference was significant. Based on the prevalence of dental fluorosis and its effect on the intelligence of children, it appears that reducing fluoride levels in drinking water and monitoring water quality are important strategies for the prevention and treatment of fluorosis.


Asunto(s)
Agua Potable , Intoxicación por Flúor , Fluorosis Dental , Niño , Humanos , Fluoruros/análisis , Fluorosis Dental/epidemiología , Agua Potable/análisis , Salud Infantil , China/epidemiología , Prevalencia
13.
Biomedicines ; 11(9)2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37760781

RESUMEN

BACKGROUND: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. OBJECTIVES: The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. METHODS: Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. RESULTS: CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. CONCLUSION: Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future.

14.
Cell Rep ; 42(9): 113145, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37725512

RESUMEN

The conserved WD40-repeat protein WDR5 interacts with multiple proteins both inside and outside the nucleus. However, it is currently unclear whether and how the distribution of WDR5 between complexes is regulated. Here, we show that an unannotated microprotein EMBOW (endogenous microprotein binder of WDR5) dually encoded in the human SCRIB gene interacts with WDR5 and regulates its binding to multiple interaction partners, including KMT2A and KIF2A. EMBOW is cell cycle regulated, with two expression maxima at late G1 phase and G2/M phase. Loss of EMBOW decreases WDR5 interaction with KIF2A, aberrantly shortens mitotic spindle length, prolongs G2/M phase, and delays cell proliferation. In contrast, loss of EMBOW increases WDR5 interaction with KMT2A, leading to WDR5 binding to off-target genes, erroneously increasing H3K4me3 levels, and activating transcription of these genes. Together, these results implicate EMBOW as a regulator of WDR5 that regulates its interactions and prevents its off-target binding in multiple contexts.


Asunto(s)
Cromatina , Péptidos y Proteínas de Señalización Intracelular , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Proliferación Celular , Huso Acromático , Cinesinas/genética , Micropéptidos
15.
Discov Oncol ; 14(1): 156, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37639070

RESUMEN

BACKGROUND: 3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs). METHODS: CCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model. RESULTS: Our data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self-renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability. CONCLUSIONS: Microserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method.

16.
Biomater Sci ; 11(14): 4822-4826, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37365951

RESUMEN

Low drug loading and instability of liposomes are two main challenges in the clinic. Herein, a liposomal platform from alternative pyridine-appended disulfidephospholipid (Pyr-SS-PC) was developed for delivering camptothecin (CPT) with high loading and stability. These Pyr-SS-PC lipids with π-π stacking open a general gate in the delivery of aromatic ring-containing drugs.


Asunto(s)
Camptotecina , Liposomas , Piridinas , Estabilidad de Medicamentos
17.
Nanomedicine ; 53: 102693, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37343780

RESUMEN

Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment.


Asunto(s)
Liposomas , Melanoma , Humanos , Liposomas/farmacología , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Lípidos/farmacología , Microambiente Tumoral
18.
Front Pharmacol ; 14: 1076815, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37229244

RESUMEN

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification. Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein-protein interaction (PPI) networks and further screening of core targets. Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that "steroid receptor activity" and the "PI3K/AKT signaling pathway" were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase. Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 300: 122904, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37229941

RESUMEN

In this work, three Schiff-based fluorescent probes with aggregation-induced emission (AIE) and excited intramolecular proton transfer (ESIPT) characters were synthesized by grafting 2-aminobenzothiazole group onto 4-substituted salicylaldehydes. More important, a rare tri-responsive fluorescent probe (SN-Cl) was developed by purposeful variation of substituents in the molecule. It could selectively identify Pb2+, Ag+ and Fe3+ in different solvent systems or with the help of masking agent and show complete fluorescence enhancement without interference of other ions. Meanwhile, the other two probes (SN-ON and SN-N) could only recognize Pb2+ in DMSO/Tris-HCl buffer (3: 7, v/v, pH = 7.4). According to Job's plot, density functional theory (DFT) calculations and NMR analysis, coordination between SN-Cl and Pb2+/Ag+/Fe3+ was determined. The LOD values for three ions were as low as 0.059 µM, 0.012 µM and 8.92 µM, respectively. Ideally, SN-Cl showed satisfactory performance in real water samples detection and test paper experiments for three ions. Also, SN-Cl could be used as an excellent imaging agent for Fe3+ in HeLa cells. Therefore, SN-Cl has the ability to be a "single fluorescent probe for three targets".


Asunto(s)
Colorantes Fluorescentes , Protones , Humanos , Colorantes Fluorescentes/química , Plomo , Bases de Schiff/química , Células HeLa , Espectrometría de Fluorescencia/métodos , Iones
20.
Oncol Rep ; 49(3)2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36799194

RESUMEN

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, concerning the cell proliferation and migration assay data shown in Figs. 6D and 7B, there were a pair of panels showing overlapping data, such that the same data had apparently been selected to show the results from different experiments. Subsequently, the authors referred back to their original data, and identified further incorrectly assembled data panels in Figs. 3B and 7B. The corrected versions of Fig. 3B (showing the correct data for the 'AC245100.4 / PC3 / 0 h' scratch­wound assay data panel), Fig. 6D (showing the correct data for the 'PC3 / NC­mimic' and 'DU­145 / NC­inhibitor' data panels) and Fig. 7D (showing the correct data for the 'PC3 / 24 h / Inhibitor­miR­145­5p + siAC245100.4' data panel) are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not grossly affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 45: 619­629, 2021; DOI: 10.3892/or.2020.7894].

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