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1.
Proc Natl Acad Sci U S A ; 121(2): e2316396121, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38165937

RESUMEN

Plant epidermal cell walls maintain the mechanical integrity of plants and restrict organ growth. Mechanical analyses can give insights into wall structure and are inputs for mechanobiology models of plant growth. To better understand the intrinsic mechanics of epidermal cell walls and how they may accommodate large deformations during growth, we analyzed a geometrically simple material, onion epidermal strips consisting of only the outer (periclinal) cell wall, ~7 µm thick. With uniaxial stretching by >40%, the wall showed complex three-phase stress-strain responses while cyclic stretching revealed reversible and irreversible deformations and elastic hysteresis. Stretching at varying strain rates and temperatures indicated the wall behaved more like a network of flexible cellulose fibers capable of sliding than a viscoelastic composite with pectin viscosity. We developed an analytic framework to quantify nonlinear wall mechanics in terms of stiffness, deformation, and energy dissipation, finding that the wall stretches by combined elastic and plastic deformation without compromising its stiffness. We also analyzed mechanical changes in slightly dehydrated walls. Their extension became stiffer and more irreversible, highlighting the influence of water on cellulose stiffness and sliding. This study offers insights into the structure and deformation modes of primary cell walls and presents a framework that is also applicable to tissues and whole organs.


Asunto(s)
Pared Celular , Celulosa , Celulosa/química , Pared Celular/química , Membrana Celular , Pectinas , Epidermis de la Planta
2.
Proc Natl Acad Sci U S A ; 121(11): e2307803120, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38437542

RESUMEN

Lipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids for gene therapy as exemplified by the worldwide rollout of LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still a major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components of which adsorb onto the LNP surface forming a layer of biomolecules termed the "biomolecular corona (BMC)" which affects LNP stability, biodistribution, and tissue tropism. The mechanisms by which the BMC influences tissue- and cell-specific targeting remains largely unknown, due to the technical challenges in isolating LNPs and their corona from complex biological media. In this study, we present a new technique that utilizes magnetic LNPs to isolate LNP-corona complexes from unbound proteins present in human serum. First, we developed a magnetic LNP formulation, containing >40 superparamagnetic iron oxide nanoparticles (IONPs)/LNP, the resulting LNPs containing iron oxide nanoparticles (IOLNPs) displayed a similar particle size and morphology as LNPs loaded with nucleic acids. We further demonstrated the isolation of the IOLNPs and their corresponding BMC from unbound proteins using a magnetic separation (MS) system. The BMC profile of LNP from the MS system was compared to size exclusion column chromatography and further analyzed via mass spectrometry, revealing differences in protein abundances. This new approach enabled a mild and versatile isolation of LNPs and its corona, while maintaining its structural integrity. The identification of the BMC associated with an intact LNP provides further insight into LNP interactions with biological fluids.


Asunto(s)
Liposomas , Nanopartículas , Ácidos Nucleicos , Humanos , Distribución Tisular , Fenómenos Magnéticos
3.
Liver Int ; 44(8): 1937-1951, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38606676

RESUMEN

BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.


Asunto(s)
Autofagia , Células Estrelladas Hepáticas , Hidroxicloroquina , Cirrosis Hepática , Hidroxicloroquina/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Animales , Autofagia/efectos de los fármacos , Ratones , Cirrosis Hepática/tratamiento farmacológico , Liposomas , Nanopartículas , Masculino , Modelos Animales de Enfermedad , Humanos , Tioacetamida , Ratones Endogámicos C57BL
4.
J Nanobiotechnology ; 22(1): 181, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622641

RESUMEN

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.


Asunto(s)
Ácidos Borónicos , Curcumina , Placa Dental , Glicoles , Nanopartículas Multifuncionales , Nanopartículas , Periodontitis , Humanos , Curcumina/farmacología , Especies Reactivas de Oxígeno , Ésteres , Periodontitis/tratamiento farmacológico , Ácido Hialurónico/farmacología
5.
BMC Nephrol ; 25(1): 75, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429741

RESUMEN

BACKGROUND: Peritoneal dialysis (PD) remains underutilised in Germany, prompting the initiation of the Sustainable Intensification of Peritoneal Dialysis in Schleswig-Holstein (SKIP-SH) project. The SKIP-SH cohort study aims to demonstrate the presumed benefits of PD, including enhanced quality of life and reduced healthcare personnel requirements, and to generate data to strengthen the use of PD. METHODS: The prospective SKIP-SH cohort study recruits patients with advanced chronic kidney disease (CKD) and their caregivers. Comprehensive data, including demographic information, medical history, clinical course, laboratory data, and quality-of-life assessments, are collected. Additionally, biomaterials will be obtained. Primary study objectives are documenting the clinical course and complications, time on therapy for new dialysis patients, reasons influencing treatment modality choices, circumstances at the initiation of dialysis, and quality of life for patients with CKD and their caregivers. The collected biomaterials will serve as a basis for further translational research. Secondary objectives include identifying factors impacting disease-related quality of life, clinical complications, and therapy dropout, estimating ecological footprints, and evaluating healthcare costs and labour time for initiating and sustaining PD treatment. DISCUSSION: PD is notably underutilised in Germany. The current therapy approach for advanced CKD often lacks emphasis on patient-focused care and quality-of-life considerations. Furthermore, adequate explorative research programs to improve our knowledge of mechanisms leading to disease progression and therapy failure in PD patients are scarce. The overarching goal of the SKIP-SH cohort study is to address the notably low PD prevalence in Germany whilst advocating for a shift towards patient-focused care, quality-of-life considerations, and robust translational research. TRIAL REGISTRATION: This study was registered with the German trial registry (Deutsches Register klinischer Studien) on November 7, 2023, under trial number DRKS00032983.


Asunto(s)
Fallo Renal Crónico , Diálisis Peritoneal , Insuficiencia Renal Crónica , Humanos , Diálisis Renal/efectos adversos , Fallo Renal Crónico/epidemiología , Estudios de Cohortes , Calidad de Vida , Estudios Prospectivos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Progresión de la Enfermedad , Materiales Biocompatibles
6.
Protein Expr Purif ; 204: 106231, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36623711

RESUMEN

Recombinant virus-like particles (VLP) with single capsid protein have been successfully produced through prokaryotic system, but for those with multiple capsid proteins such as the foot-and-mouth disease virus (FMDV), this approach is more challenging. In this study, in vitro assembly of FMDV VLP was investigated with its capsids VP1, VP2 and VP3 separately expressed as inclusion bodies. After extraction and solubilization, three capsids were purified in denatured state through a flow-through model, increasing its purity to 90%. VLP assembly for FMDV was observed after diluting the mixture of denatured capsids in the ration of 1: 1: 1, while no VLP appeared if the separately diluted and refolded capsids were co-incubated. This result suggests certain synergetic interactions exist among the three capsids, which are crucial for FMDV VLP assembly. Sodium chloride and capsid protein concentration both greatly affect the assembling efficiency. After purification through size exclusion chromatography, VLP with similar diameter and morphology as inactivated FMDV were obtained, which elicited high IgG titers and B cell activation when vaccinated in mouse. It could also induce specific humoral and cellular immune responses in splenocytes proliferative experiments. Our study demonstrated the feasibility of in vitro assembling FMDV VLP from inclusion bodies of VP1, VP2 and VP3 for the first time.


Asunto(s)
Partículas Similares a Virus Artificiales , Proteínas de la Cápside , Virus de la Fiebre Aftosa , Fiebre Aftosa , Ensamble de Virus , Animales , Ratones , Proteínas de la Cápside/química , Fiebre Aftosa/prevención & control , Virus de la Fiebre Aftosa/química , Cuerpos de Inclusión , Partículas Similares a Virus Artificiales/química
7.
Liver Int ; 43(2): 329-339, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36453086

RESUMEN

BACKGROUND AND AIMS: Myeloid-derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells. METHODS: Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks. RESULTS: The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance. CONCLUSIONS: These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.


Asunto(s)
Hepatitis B Crónica , Células Supresoras de Origen Mieloide , Humanos , Antígenos de Superficie de la Hepatitis B , Antivirales , Antígenos e de la Hepatitis B , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Virus de la Hepatitis B/genética , ADN Viral
8.
BMC Ophthalmol ; 23(1): 418, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37858210

RESUMEN

BACKGROUND: Xen Gel Stent implant is a new minimally invasive surgical treatment for glaucoma that has been proven effectiveness and safety profile. However, it may also lead to some complications. Xen Gel Stent occlusion is a relatively rare complication reported less frequently and has limited treatment experience. In our case report, we proposed a novel surgical treatment using a 10 - 0 nylon suture to successfully recanalize the occluded Xen45 Gel Stent. CASE PRESENTATION: A 16-year-old female patient had bilateral juvenile glaucoma for the past 5 years. Her right eye had undergone three glaucoma surgeries but failed. At a presentation to our hospital, the right eye's intraocular pressure (IOP) was 30 mmHg despite applying four different active principles. Xen45 Gel Stent implant was chosen for treatment, but six days after implantation, the IOP rose to 40 mmHg as a result of an anterior chamber tip occlusion of the Xen45 Gel Stent. Nd: YAG laser shockwave therapy was attempted but failed. The patient eventually had to return to the operating room for a revision procedure. The Xen45 Gel Stent was recanalized from the ab externo by making an L-shaped conjunctival incision at the fornix base and threading a 10 - 0 nylon suture through it. The IOP was successfully controlled in the 11-month follow-up without medication. CONCLUSION: If postoperative occlusion arises after Xen45 Gel Stent implantation, surgery using 10 - 0 nylon suture to recanalize Xen45 Gel Stent should be considered as a relatively safe, effective that does not require removal of Xen45 Gel Stent.


Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma , Humanos , Femenino , Adolescente , Nylons , Resultado del Tratamiento , Glaucoma/cirugía , Presión Intraocular , Stents , Suturas
9.
Ecotoxicol Environ Saf ; 258: 114965, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37141682

RESUMEN

The massive accumulation of polyethylene (PE) in the natural environment has caused persecution to the ecological environment. At present, the mechanism of microbial degradation of PE remains unclear, and the related enzymes for degrading PE need to be further explored. In this study, a strain of Klebsiella pneumoniae Mk-1 which can effectively degrade PE was obtained from the soil. The degradation performance of the strains was evaluated by weight loss rate, SEM, ATR/FTIR, WCA, and GPC. The key gene of PE degradation in the strain was further searched, which may be the laccase-like multi-copper oxidase gene. Then, the laccase-like multi-copper oxidase gene (KpMco) was successfully expressed in E.coli and its laccase activity was verified, which reached 85.19 U/L. The optimum temperature and pH of the enzyme are 45 °C and 4.0, respectively; it shows good stability at 30-40 °C and pH 4.5-5.5; Mn2+ and Cu2+ can activate the enzyme effect. After the enzyme was applied to the degradation of PE film, it was found that the laccase-like multi-copper oxidase did have a certain degradation effect on PE film. This study provides new strain and enzyme gene resources for the biodegradation of PE, thereby promoting the process of PE biodegradation.


Asunto(s)
Polietileno , Suelo , Polietileno/metabolismo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Lacasa/genética , Lacasa/metabolismo , Biodegradación Ambiental
10.
Molecules ; 28(9)2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37175098

RESUMEN

With the increased incidence of wine fraud, a fast and reliable method for wine certification has become a necessary prerequisite for the vigorous development of the global wine industry. In this study, a classification strategy based on three-dimensional fluorescence spectroscopy combined with chemometrics was proposed for oak-barrel and stainless steel tanks with oak chips aged wines. Principal component analysis (PCA), partial least squares analysis (PLS-DA), and Fisher discriminant analysis (FDA) were used to distinguish and evaluate the data matrix of the three-dimensional fluorescence spectra of wines. The results showed that FDA was superior to PCA and PLS-DA in classifying oak-barrel and stainless steel tanks with oak chips aged wines. As a general conclusion, three-dimensional fluorescence spectroscopy can provide valuable fingerprint information for the identification of oak-barrel and stainless steel tanks with oak chips aged wines, while the study will provide some theoretical references and standards for the quality control and quality assessment of oak-barrel aged wines.


Asunto(s)
Quercus , Vino , Vino/análisis , Acero Inoxidable , Quercus/química , Espectrometría de Fluorescencia , Quimiometría , Madera/química
11.
J Headache Pain ; 24(1): 50, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37165344

RESUMEN

BACKGROUND: Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI). METHODS: Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM. RESULTS: Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats. CONCLUSIONS: These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.


Asunto(s)
Dolor Crónico , Hiperalgesia , Ratas , Animales , Hiperalgesia/inducido químicamente , Núcleo Espinal del Trigémino/metabolismo , Receptores de Serotonina 5-HT3/metabolismo , Receptores de Serotonina 5-HT3/uso terapéutico , Serotonina/metabolismo , Ratas Sprague-Dawley , Dolor Facial/etiología , Dolor Crónico/etiología
12.
Zhongguo Zhong Yao Za Zhi ; 48(22): 6075-6081, 2023 Nov.
Artículo en Zh | MEDLINE | ID: mdl-38114214

RESUMEN

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.


Asunto(s)
Aceite de Ricino , Polietilenglicoles , Polietilenglicoles/química , Metanol , Tensoactivos/química , Solventes , Agua/química , Emulsiones/química
13.
J Am Chem Soc ; 144(43): 19896-19909, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36256447

RESUMEN

Switchable catalysis, in combination with epoxide-involved ring-opening (co)polymerization, is a powerful technique that can be used to synthesize various oxygen-rich block copolymers. Despite intense research in this field, the sequence-controlled polymerization from epoxide congeners has never been realized due to their similar ring-strain which exerts a decisive influence on the reaction process. Recently, quaternary ammonium (or phosphonium)-containing bifunctional organoboron catalysts have been developed by our group, showing high efficiency for various epoxide conversions. Herein, we, for the first time, report an operationally simple pathway to access well-defined polyether-block-polycarbonate copolymers from mixtures of epoxides by switchable catalysis, which was enabled through thermodynamically and kinetically preferential ring-opening of terminal epoxides or internal epoxides under different atmospheres (CO2 or N2) using one representative bifunctional organoboron catalyst. This strategy shows a broad substrate scope as it is suitable for various combinations of terminal epoxides and internal epoxides, delivering corresponding well-defined block copolymers. NMR, MALDI-TOF, and gel permeation chromatography analyses confirmed the successful construction of polyether-block-polycarbonate copolymers. Kinetic studies and density functional theory calculations elucidate the reversible selectivity between different epoxides in the presence/absence of CO2. Moreover, by replacing comonomer CO2 with cyclic anhydride, the well-defined polyether-block-polyester copolymers can also be synthesized. This work provides a rare example of sequence-controlled polymerization from epoxide mixtures, broadening the arsenal of switchable catalysis that can produce oxygen-rich polymers in a controlled manner.


Asunto(s)
Dióxido de Carbono , Compuestos Epoxi , Compuestos Epoxi/química , Cinética , Dióxido de Carbono/química , Oxígeno , Catálisis , Polímeros/química , Carbonatos
14.
J Med Virol ; 94(9): 4449-4458, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35610746

RESUMEN

A variant in signal transducer and activator of transcription 4 (STAT4) was reported to correlate with the response of interferon-α (IFN-α) in a retrospective study in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (CHB) patients. Here, we conducted a prospective study to analyze the effect of STAT4 genetic polymorphism on the response of pegylated interferon-α-2a (PegIFN-α-2a) in HBeAg-positive patients. A prospective, multicenter, open-label, parallel cohort study was performed. One hundred and fifty treatment-naïve and 156 nucleos(t)ide analog (NA)-experienced HBeAg-positive CHB patients were enrolled, respectively. All patients received PegIFN-α-2a treatment for 48 weeks and 24-week follow-up post PegIFN-α-2a treatment. Before treatment, STAT4 genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the GT/TT group than in the GG group at week 72 (p = 0.002 and p = 0.023) in treatment-naïve patients. In NA-experienced patients, the HBeAg seroconversion rate in the GT/TT group was higher than that in the GG group at week 72 (p = 0.005). STAT4 rs7574865 gene polymorphism was the strongest independent predictor of HBeAg seroconversion in both paralleled cohorts. Also, patients in the GT/TT group had a higher hepatitis B surface antigen loss rate than in the GG group in the study. There was no significant difference in adverse events between GG and GT/TT groups. This prospective cohort study confirmed that STAT4 rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of naïve and NA-experienced HBeAg-positive CHB patients treated with PegIFN-α-2a.


Asunto(s)
Antivirales , Hepatitis B Crónica , Interferón-alfa , Factor de Transcripción STAT4 , Antivirales/uso terapéutico , Estudios de Cohortes , ADN Viral , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Polimorfismo Genético , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factor de Transcripción STAT4/genética , Seroconversión , Resultado del Tratamiento
15.
Langmuir ; 38(46): 14036-14043, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36367350

RESUMEN

Nucleic acid therapeutics represent a major advance toward treating diseases at their root cause. However, nucleic acids are prone to degradation by serum endonucleases, clearance through the immune system, and rapid degradation in complex medium. To overcome these barriers, nucleic acids frequently include chemical modifications to improve stability or decrease immune responses. Lipid nanoparticles (LNPs) have enabled a dramatic reduction in the dose required to achieve a therapeutic effect by protecting these nucleic acids and improving their intracellular delivery. It has been assumed thus far that nonspecific ionic interactions drive LNP formation and chemical modifications to the nucleic acid backbone to confer improved stability do not impact LNP delivery in any way. Here, we demonstrate that these chemical modifications do impact LNP morphology substantially, and phosphorothioate modifications produce stronger interactions with ionizable amino lipids, resulting in enhanced entrapment. This work represents a major first step toward greater understanding of the interaction between the lipid components and nucleic acids within an LNP.


Asunto(s)
Nanopartículas , Ácidos Nucleicos , Liposomas , ARN Interferente Pequeño
16.
Rapid Commun Mass Spectrom ; 36(18): e9351, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-35802517

RESUMEN

RATIONALE: Thermogravimetry (TG) combined with electrospray and atmospheric chemical ionization (ESI+APCI) mass spectrometry (MS) was developed to rapidly characterize thermal decomposition products of synthetic polymers and plastic products. The ESI-based TG-MS method is useful for characterizing thermally labile, nonvolatile, and polar compounds over an extensive mass range; and the APCI-based TG-MS counterpart is useful for characterizing volatile and nonpolar compounds. Both polar and nonpolar compounds can be simultaneously detected by ESI+APCI-based TG-MS. METHODS: Analytes with different volatility were produced from TG operated at different temperatures, which were delivered through a heated stainless-steel tube to the ESI+APCI source where they reacted with the primary charged species generated from electrospray and atmospheric pressure chemical ionization (ESI+APCI) of solvent and nitrogen. The analyte ions were then detected by an ion trap mass spectrometer. RESULTS: A semi-volatile PEG 600 standard was used as the sample and protonated and sodiated molecular ions together with adduct ions including [(PEG)n + 15]+ , [(PEG)n + 18]+ , and [(PEG)n + 29]+ were detected by TG-ESI+APCI-MS. The technique was further utilized to characterize thermal decomposition products of nonvolatile polypropylene glycol (PPG) and polystyrene (PS) standards, as well as a PS-made water cup and coffee cup lid. The characteristic fragments of PPG and PS with mass differences of 58 and 104 between respective ion peaks were detected at the maximum decomposition temperature (Tmax ). CONCLUSIONS: The information obtained from the TG-ESI+APCI-MS analysis is useful in rapidly distinguishing different types of polymers and their products. In addition, the signals of the additives in the polymer products, including antioxidants and plasticizers, were also detected before the TG temperature reached Tmax .


Asunto(s)
Presión Atmosférica , Espectrometría de Masa por Ionización de Electrospray , Polímeros , Solventes , Espectrometría de Masa por Ionización de Electrospray/métodos , Termogravimetría
17.
Sensors (Basel) ; 20(4)2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32093154

RESUMEN

High-performance flexible strain sensors are playing an increasingly important role in wearable electronics, such as human motion detection and health monitoring, with broad application prospects. This study developed a flexible resistance strain sensor with a porous structure composed of carbon black and multi-walled carbon nanotubes. A simple and low-cost spraying method for the surface of a porous polydimethylsiloxane substrate was used to form a layer of synergized conductive networks built by carbon black and multi-walled carbon nanotubes. By combining the advantages of the synergetic effects of mixed carbon black and carbon nanotubes and their porous polydimethylsiloxane structure, the performance of the sensor was improved. The results show that the sensor has a high sensitivity (GF) (up to 61.82), a wide strain range (0%-130%), a good linearity, and a high stability. Based on the excellent performance of the sensor, the flexible strain designed sensor was installed successfully on different joints of the human body, allowing for the monitoring of human movement and human respiratory changes. These results indicate that the sensor has promising potential for applications in human motion monitoring and physiological activity monitoring.


Asunto(s)
Técnicas Biosensibles/métodos , Monitoreo Fisiológico/métodos , Nanotubos de Carbono/análisis , Dispositivos Electrónicos Vestibles , Dimetilpolisiloxanos/química , Humanos , Porosidad
18.
Small ; 15(50): e1905209, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31631563

RESUMEN

The bidirectional transport of nanoparticles and biological cells is of great significance in efficient biological assays and precision cell screening, and can be achieved with optical conveyor belts in a noncontact and noninvasive manner. However, implantation of these belts into biological systems can present significant challenges owing to the incompatibility of the artificial materials. In this work, an optical conveyor belt assembled from natural biological cells is proposed. The diameter of the belt (500 nm) is smaller than the laser wavelength (980 nm) and, therefore, the evanescent wave stably traps the nanoparticles and cells on the belt surface. By adjusting the relative power of the lasers injected into the belt, the particles or cells can be bidirectionally transported along the bio-conveyor belt. The experimental results are numerically interpreted and the transport velocities are investigated based on simulations. Further experiments show that the bio-conveyor belt can also be assembled with mammalian cells and then applied to dynamic cell transport in vivo. The bio-conveyor belt might provide a noninvasive and biocompatible tool for biomedical assays, drug delivery, and biological nanoarchitectonics.


Asunto(s)
Células/metabolismo , Nanopartículas/química , Adulto , Animales , Transporte Biológico , Simulación por Computador , Escherichia coli/metabolismo , Humanos , Masculino , Poliestirenos/metabolismo , Pez Cebra
19.
Anesth Analg ; 128(2): 349-357, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30169410

RESUMEN

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD. METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of ≤-1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of AM (morning) to PM (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening. RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%-24.76%) of patients 1 week after the operation. A higher preoperative AM/PM salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20-2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19-2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol AM/PM ratio in individuals with POCD was 0.72 (95% CI, 0.56-0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%. CONCLUSIONS: The preoperative salivary cortisol AM/PM ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.


Asunto(s)
Disfunción Cognitiva/metabolismo , Hidrocortisona/metabolismo , Complicaciones Posoperatorias/metabolismo , Cuidados Preoperatorios/tendencias , Saliva/metabolismo , Anciano , Ritmo Circadiano/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Femenino , Humanos , Hidrocortisona/análisis , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/psicología , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/psicología , Saliva/química
20.
Small ; 13(37)2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28783253

RESUMEN

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome-based nanoparticle (designated as LipoMB/CaO2 ) with O2 self-sufficient property for dual-stage light-driven PDT is demonstrated to address this problem. Through a short time irradiation, 1 O2 activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO2 with H2 O, resulting in accelerated O2 production. Accelerated O2 level further regulates hypoxic tumor microenvironment and in turn improves 1 O2 generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO2 to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side-effect. The O2 self-sufficient LipoMB/CaO2 nanoplatform with dual-stage light manipulation is a successful attempt for PDT against hypoxic tumor.


Asunto(s)
Luz , Nanopartículas/química , Oxígeno/química , Fotoquimioterapia , Hipoxia Tumoral , Animales , Apoptosis , Peso Corporal , Compuestos de Calcio/química , Línea Celular Tumoral , Liposomas , Azul de Metileno , Ratones , Nanopartículas/ultraestructura , Necrosis , Óxidos/química , Carga Tumoral , Difracción de Rayos X
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