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1.
Opt Express ; 27(24): 35203-35215, 2019 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-31878693

RESUMEN

Conventional optofluidic lens usually has only one interface, which means that the zoom range is small, and the ability to correct aberrations is poor. In this paper, we propose a hybrid driving variable-focus optofluidic lens. It has one water-oil interface shifted by an applied voltage and one tunable Polydimethylsiloxane (PDMS) lens deformed by pumping liquid in or out of the cavity. The proposed lens combines the advantages of electrowetting lens and mechanical lens. Therefore, it can provide a large focal length tuning range with good image quality. The shortest positive and negative focal length are ∼6.02 mm and ∼-11.15 mm, respectively. The maximum resolution of our liquid lens can be reached 18 lp/mm. We also designed and fabricated a zoom system using the hybrid driving variable-focus optofluidic lens. In the experiment, the zoom range of the system is 14 mm∼30 mm and the zoom ratio is ∼2.14× without any mechanical moving parts. Its applications for zoom telescope system and zoom microscope and so on are foreseeable.

2.
Ophthalmology ; 125(9): 1421-1430, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29759820

RESUMEN

PURPOSE: To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO). DESIGN: Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. PARTICIPANTS: This study included 2 kinds of human RHO mutation knock-in mouse models: RhoP23H and RhoD190N. In total, 23 RhoP23H/P23H, 43 RhoP23H/+, and 31 RhoD190N/+ mice were used for analysis. METHODS: This study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA. MAIN OUTCOME MEASURES: Electroretinographic and histologic analysis. RESULTS: The thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both RhoP23H and RhoD190N disease models were preserved more significantly using ablate-and-replace gene therapy (P < 0.001), but not by gene replacement monotherapy. CONCLUSIONS: As a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest.


Asunto(s)
Terapia Genética/métodos , Retinitis Pigmentosa/genética , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Modelos Animales de Enfermedad , Electrorretinografía , Vectores Genéticos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/terapia
3.
Graefes Arch Clin Exp Ophthalmol ; 256(3): 583-588, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29376197

RESUMEN

PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities. METHODS: We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing. RESULTS: Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 µm2 and the average central corneal thickness (CCT) was 551 ± 33 µm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.


Asunto(s)
ADN Mitocondrial/genética , Epitelio Corneal/diagnóstico por imagen , Síndrome Endotelial Iridocorneal/genética , Enfermedades Mitocondriales/genética , Mutación Puntual , Análisis Mutacional de ADN , Humanos , Síndrome Endotelial Iridocorneal/metabolismo , Síndrome Endotelial Iridocorneal/patología , Microscopía Acústica , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
4.
Ann Neurol ; 80(3): 461-5, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27422481

RESUMEN

Essential tremor (ET) patients have abnormal climbing fiber (CF) synapses in the parallel fiber territory in the cerebellum, and these abnormal CF synapses are inversely correlated with tremor severity. We therefore examined CF synaptic pathology in ET cases with and without thalamic deep brain stimulation (DBS) and assessed the association with tremor severity. We found that CF synaptic pathology was inversely correlated with tremor severity in ET cases without DBS, and this correlation disappeared in ET cases with DBS. Our data suggest that DBS might have effects in modulating excitatory synapses in ET cerebellum, in addition to its symptomatic effects on tremor. Ann Neurol 2016;80:461-465.


Asunto(s)
Enfermedades Cerebelosas/patología , Estimulación Encefálica Profunda , Temblor Esencial/fisiopatología , Temblor Esencial/terapia , Fibras Nerviosas/patología , Sinapsis/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad
5.
Analyst ; 141(5): 1633-6, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26844973

RESUMEN

Bacteria colonies were analyzed using paper spray ionization coupled with a portable mass spectrometer. The spectra were averaged and processed using multivariate analysis to discriminate between different species of bacteria based on their unique phospholipid profiles. Full scan mass spectra and product ion MS/MS data were compared to those recorded using a benchtop linear ion trap mass spectrometer.


Asunto(s)
Bacterias/aislamiento & purificación , Espectrometría de Masas/instrumentación , Miniaturización , Bacterias/química , Papel , Factores de Tiempo
6.
Analyst ; 140(3): 696-700, 2015 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-25475256

RESUMEN

A method is presented in which ions are generated and manipulated in the ambient environment using polymeric electrodes produced with a consumer-grade 3D printer. The ability to focus, separate, react, and detect ions in the ambient environment is demonstrated and the data agree well with simulated ion behaviour.


Asunto(s)
Electrodos , Iones , Plásticos , Polímeros/química , Compuestos de Amonio Cuaternario/análisis , Compuestos de Amonio Cuaternario/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Aire
7.
Int J Pharm ; 653: 123844, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38272193

RESUMEN

Discovering new ligands for enhanced drug uptake and delivery has been the core interest of the drug delivery field. This study capitalizes on the natural "eat-me" signal of calreticulin (CRT), proposing a novel strategy for functionalizing liposomes to improve cellular uptake. CRT is presented on the surfaces of apoptotic cells, and it plays a crucial role in immunogenic cell death (ICD). This is because it is essential for antigen uptake via low-density lipoprotein (LDL) receptor-mediated phagocytosis. Inspired by this mechanism, we interrogated CRT's "eat-me" feature using CRT-derived peptides to functionalize liposomes. We studied liposomal formulation stability, properties, cellular uptake, toxicity, and intracellular trafficking in dendritic cells. We identified key peptide fragments of CRT, specifically from the hydrophilic P-domain, that are compatible with liposomal formulations. Contrary to the more hydrophobic N-domain peptides, the P-domain peptides induced significantly higher liposomal uptake in DC2.4 dendritic cells than cationic DOTAP and anionic DPPG liposomes without inducing toxicity. The P-domain-derived peptides led to enhanced liposomal uptake into DC2.4 dendritic cells compared to the standard DPPC liposomes. The uptake can be partially blocked by the receptor-associated protein (RAP). Upon internalization, P-domain-peptide-decorated liposomes showed higher co-localization with lysosomes compared to the standard DPPC liposomes. Our findings illuminate CRT's operational role and identify P-domain peptides as promising agents for developing biomimetic drug delivery systems that can potentially replicate CRT's "eat-me" function.


Asunto(s)
Calreticulina , Liposomas , Liposomas/química , Péptidos/química , Sistemas de Liberación de Medicamentos , Células Dendríticas
8.
J Control Release ; 375: 366-388, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39179112

RESUMEN

Recent advancements in RNA therapeutics highlight the critical need for precision gene delivery systems that target specific organs and cells. Lipid nanoparticles (LNPs) have emerged as key vectors in delivering mRNA and siRNA, offering protection against enzymatic degradation, enabling targeted delivery and cellular uptake, and facilitating RNA cargo release into the cytosol. This review discusses the development and optimization of organ- and cell-specific LNPs, focusing on their design, mechanisms of action, and therapeutic applications. We explore innovations such as DNA/RNA barcoding, which facilitates high-throughput screening and precise adjustments in formulations. We address major challenges, including improving endosomal escape, minimizing off-target effects, and enhancing delivery efficiencies. Notable clinical trials and recent FDA approvals illustrate the practical applications and future potential of LNP-based RNA therapies. Our findings suggest that while considerable progress has been made, continued research is essential to resolve existing limitations and bridge the gap between preclinical and clinical evaluation of the safety and efficacy of RNA therapeutics. This review highlights the dynamic progress in LNP research. It outlines a roadmap for future advancements in RNA-based precision medicine.

9.
Biol Open ; 13(5)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38713004

RESUMEN

Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the ß-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis. Ouabain blocks macropinocytosis, which is an essential step in Wnt signaling, probably explaining the strong effects of Ouabain on this pathway. In Xenopus embryos, brief Ouabain treatment at the 32-cell stage, critical for the earliest Wnt signal in development-inhibited brains, could be reversed by treatment with Lithium chloride, a Wnt mimic. Inhibiting membrane trafficking may provide a way of targeting Wnt-driven cancers.


Asunto(s)
Neoplasias del Colon , Pinocitosis , ATPasa Intercambiadora de Sodio-Potasio , Vía de Señalización Wnt , Animales , Humanos , Línea Celular Tumoral , Neoplasias del Colon/metabolismo , Neoplasias del Colon/etiología , Ouabaína/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Xenopus
10.
Front Plant Sci ; 15: 1332443, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38504896

RESUMEN

Introduction: Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus. Methods: Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia. The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics. Results: The newly discovered species, Salvia guidongensis, exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria, S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia, suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis, comparing them with those of closely related species. Discussion: The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia.

11.
Acta Crystallogr C Struct Chem ; 80(Pt 8): 366-374, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38967632

RESUMEN

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

12.
Heliyon ; 10(9): e30505, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38726194

RESUMEN

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

13.
Analyst ; 138(16): 4624-30, 2013 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-23762894

RESUMEN

Rapid qualitative and quantitative analysis of 4-methylimidazole (4-MEI) in caramel and beverage samples is demonstrated using the paper spray form of ambient ionization mass spectrometry. The minimum level of pure 4-MEI detectable using multiple reaction monitoring (MRM) in a triple quadrupole instrument was 3 pg µL⁻¹ in neat solvent and 5 pg µL⁻¹ in a matrix containing caramel. This method was used to analyze 11 caramel samples for 4-MEI. After implementing effective quality control protocols, average relative standard deviations for paper spray triple quadrupole MS were less than 15% and the linear dynamic range was three orders of magnitude. Results obtained on three different days by two different analyst groups agreed closely. An ion trap tandem MS method of approximate quantitative analysis is also described and it gave similar precision to the triple quadrupole experiment when fluctuations in ion currents were cancelled by simultaneously isolating the analyte and internal standard and fragmenting both in an ion trap simultaneous MRM experiment. As another alternative, a rapid qualitative screening method based on the use of high-resolution measurements instead of tandem mass spectrometry using an Orbitrap was also tested and found to give a detection limit of 100 pg µL⁻¹.


Asunto(s)
Bebidas/análisis , Carbohidratos/análisis , Imidazoles/análisis , Papel , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masas/métodos
14.
Analyst ; 138(16): 4443-7, 2013 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-23774310

RESUMEN

An ambient method for rapid monitoring and quantitation of drugs of abuse in dried blood spots was developed using paper spray tandem mass spectrometry (PS-MS).


Asunto(s)
Drogas Ilícitas/sangre , Papel/normas , Detección de Abuso de Sustancias/normas , Espectrometría de Masas en Tándem/normas , Animales , Bovinos , Espectrometría de Masas/métodos , Espectrometría de Masas/normas , Detección de Abuso de Sustancias/métodos , Espectrometría de Masas en Tándem/métodos
15.
Analyst ; 138(13): 3740-8, 2013 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-23675580

RESUMEN

Paper spray (PS) ambient ionization is implemented using a portable mass spectrometer and applied to the detection of alkyl quaternary ammonium salts in a complex oil matrix. These salts are commonly used as active components in the formulation of corrosion inhibitors. They were identified in oil and confirmed by their fragmentation patterns recorded using tandem mass spectrometry (MS/MS). The cations of alkyl and benzyl-substituted quaternary ammonium salts showed characteristic neutral losses of CnH2n (n carbon number of the longest chain) and C7H8, respectively. Individual quaternary ammonium compounds were detected at low concentrations (<1 ng µL(-1)) and over a dynamic range of ∼5 pg µL(-1) to 500 pg µL(-1) (ppb). Direct detection of these compounds in complex oil samples without prior sample preparation or pre-concentration was also demonstrated using a home-built miniature mass spectrometer at levels below 1 ng µL(-1).


Asunto(s)
Espectrometría de Masas/instrumentación , Papel , Corrosión , Petróleo , Compuestos de Amonio Cuaternario/análisis , Compuestos de Amonio Cuaternario/química
16.
Pharmaceutics ; 15(2)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36839795

RESUMEN

In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic cancer cell line) was significantly increased compared with the other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic cancer.

17.
Dis Markers ; 2022: 9965190, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212179

RESUMEN

Objective: This study aims to clinically investigate and compare the therapeutic effects and treatment cycle between traditional direct bonding and OrthGuide computer-aided indirect bonding in orthodontic treatment. Methods: Forty patients treated at the Department of Orthodontics, Beijing Rytime Dental Hospital between July 1, 2016, and December 31, 2019, were included. The patients were divided into a control group (n = 20, traditional direct bonding) and a test group (n = 20, OrthGuide computer-aided indirect bonding). The American Board of Orthodontics (ABO) measurement was performed on patients using Uceph cephalometric analysis software to compare intragroup and intergroup differences, and the treatment cycles of all patients were recorded. Results: After treatment, U1-NA (mm), ∠U1-SN (°), LL-EP (mm), and UL-EP (mm) in the control group were significantly lower than before treatment, and there was no significant difference in other ABO measurement indexes, while the test group showed no marked difference in all ABO measurements between pre- and posttreatment. Further, intergroup comparison showed no significant difference in ABO measurements in pre- and posttreatment between the two groups. The test group had a shorter treatment cycle than the control group, with an average treatment cycle of 21.20 ± 7.14 months in the control group and 17.17 ± 4.16 months in the test group. Conclusion: There was no significant difference in the therapeutic effects between the direct and indirect bonding techniques. However, OrthGuide computer-assisted indirect bonding demonstrated a significantly shorter treatment cycle and might be more efficient than traditional direct bonding.


Asunto(s)
Computadores , Programas Informáticos , Humanos
18.
Front Nutr ; 9: 974443, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36407550

RESUMEN

Background: Erectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied. Materials and methods: Data on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results. Results: A total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all P < 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all P < 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results. Conclusion: Increasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.

19.
Biomaterials ; 278: 121166, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34634663

RESUMEN

In this study, PEGylated poly (lactide-co-glycolide) (PLGA) thermosensitive composite hydrogels (DTgels) loaded with bispecific anti-cluster of differentiation 3 (CD3) scFv T-cell/anti-epidermal growth factor receptor (EGFR) Fab engager (BiTEE) were subcutaneously (s.c.) injected for the in situ formation of a drug deposit to resolve limitations of the clinical application of the BiTEE of a short half-life and potential side effects. Three kinds of DTgels prepared with different ratios of methoxy poly (ethylene glycol) (mPEG)-PLGA (diblock copolymer, DP) and PLGA-PEG-PLGA (triblock copolymer, TP) were designated DTgel-1, DTgel-2, and DTgel-2S. All three DTgel formulations showed thermosensitive properties with a sol-gel transition temperature at 28-34 °C, which is suitable for an injection. An in vitro release study showed that all DTgel formulations loaded with stabilized BiTEE extended the release of the BiTEE for up to 7 days. In an animal pharmacokinetics study, an s.c. injection of BiTEE/DTgel-1, BiTEE/DTgel-2, or BiTEE/DTgel-2S respectively prolonged the half-life of the BiTEE by 3.5-, 2.0-, and 2.2-fold compared to an intravenous injection of the BiTEE solution. Simultaneously, BiTEE/DTgel formulations showed almost no proinflammatory cytokine release in mice injected with T cells after s.c. administration. Results of an animal antitumor (MDA-MB-231) study indicated that an s.c. injection of the BiTEE/DTgel formulations significantly improved the antitumor efficacy compared to an intravenous (i.v.) or s.c. injection of the BiTEE solution. Moreover, BiTEE/DTgel formulations led to enhanced T-cell recruitment to solid-tumor sites. In conclusion, the in situ formation of injectable PEGylated PLGA thermosensitive hydrogels loaded with the BiTEE was successfully carried out to increase its half-life, maintain a constant blood level within therapeutic windows, and enhance T-cell recruitment to solid-tumor sites resulting in exceptional treatment efficacy.


Asunto(s)
Portadores de Fármacos , Polietilenglicoles , Animales , Diferenciación Celular , Hidrogeles , Ratones , Poliésteres , Temperatura
20.
Technol Cancer Res Treat ; 20: 15330338211035260, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34313171

RESUMEN

OBJECTIVE: The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy). METHODS: We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis. RESULTS: Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; P < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; P < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; P < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; P = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; P = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; P = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; P = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; P < 0.05). CONCLUSION: The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.


Asunto(s)
Empalme Alternativo , Biomarcadores de Tumor , Neoplasias de la Próstata Resistentes a la Castración/etiología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Isoformas de ARN , Receptores Androgénicos/genética , Humanos , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico
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