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1.
Int J Biol Macromol ; 279(Pt 3): 135311, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236948

RESUMEN

Magnetic lignin nanoparticles (MLNs) were prepared by inducing their self-assembly through lignin regeneration in the [N-methyl-2-pyrrolidone][C1-C4 carboxylic acid] ionic liquids ([NMP]ILs), which are low-cost protic ionic liquid. [NMP]ILs are self-assembling solvent that can enhance the adsorption capacity of MLNs to a greater degree than tetrahydrofuran or H2O. Additionally, the anion types of [NMP]IL greatly influence the physiochemical properties of MLNs. The MLNs prepared through self-assembly with [NMP][formate] (MLN/[NMP][For]) exhibited a higher maximum adsorption capacity (134.53 mg/g) than the [NMP]ILs of C2-C4 carboxylate anions. MLN/[NMP][For] demonstrated stable adsorption within a pH range of 6-10 or at high salt concentrations (0.01-0.5 mol/L), retaining over 80 % of its regeneration efficiency after 5 cycles. In addition, MLN/[NMP][For] selectively removed cationic dyes in mixed binary anionic-cationic dye solutions. This work demonstrated the feasibility of preparing magnetic biosorbents with good selectivity and stability though regeneration and by adjusting the anions of ionic liquids.

2.
Int J Food Sci Nutr ; : 1-11, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245583

RESUMEN

To investigate the impact of four visual elements, namely text, colour, image, and shape, on the visual perception of Chinese consumers when observing nutrition labels, as well as to enhance their attention towards nutritional information, this study examines the visual effects of nutrition labels incorporating these elements through eye movement experiments, questionnaire surveys, subjective evaluations, and other research methods. The aim is to determine the optimal design solution. The results revealed that participants displayed the highest level of attention towards the round x image group, followed by the colour group. Thus, exceptional image design and a suitable colour scheme can significantly enhance consumers' attention during browsing. This study offers valuable references and guidance for the redesign of food nutrition labels, while also presenting research insights for the application of visual perception in other domains.

3.
Front Bioeng Biotechnol ; 12: 1460870, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280342

RESUMEN

Introduction: Nanofibrous spheres, with their injectable format and biomimetic three-dimensional topologies that emulate the complexity of natural extracellular environments, have become increasingly attractive for applications in biomedical and regenerative medicine. Our research contributes to this growing field by detailing the design and fabrication of a novel series of polylactic acid/nano-hydroxyapatite (PLA/nHA) hybrid nanofibrous spheres. Methods: These advanced structures were created by integrating electrospinning and electrospray techniques, which allowed for precise control over the nanofibrous spheres, especially in size. We have conducted a comprehensive investigation into the nanofibrous spheres' capacity to deliver stem cells efficiently and maintain their viability post-implantation, as well as their potential to induce osteogenic differentiation. Results and Discussion: The results show that these nanofibrous spheres are biocompatible and injectable, effectively supporting the attachment, growth, and differentiation of bone marrow-derived mesenchymal stem cells while aiding in their targeted transportation to bone defect areas to execute their regenerative functions. The findings of this study could significantly impact the future development of biocompatible materials for a range of therapeutic applications, including bone tissue engineering and regenerative therapy.

4.
Front Immunol ; 15: 1432307, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281680

RESUMEN

Background: Limited availability and side effects of opioids have led to an increased use of non-opioid analgesia in animal disease models. However, by affecting the immune-inflammatory reactions, analgesia may disrupt the resolution of the host inflammation and modulate the survival in septic animals. This study used a clinically relevant sepsis mouse model of peritoneal contamination and infection (PCI) to investigate the antinociceptive and anti-inflammatory properties of two non-opioid analgesics. Methods: Adult C57BL/6J mice were intraperitoneally injected with a human feces suspension and received either no analgesics (Non-A), Meloxicam, or Metamizole orally. The mice were monitored for pain and illness. Mortality was assessed at 7 days post-PCI. A separate group of mice was sacrificed 24 hours after infection. Blood, peritoneal lavage fluid (PLF), liver, and spleen were harvested for pathogen load quantification via qPCR, macrophage phenotyping, neutrophil infiltration/activation, and systemic/tissue cytokine release by flow cytometry. Results: Meloxicam but not Metamizole reduced the mortality of septic mice by 31% on day 7 compared to the Non-A group. Both analgesics effectively alleviated pain but did not affect illness severity, body weight, and temperature. Meloxicam quadrupled the bacterial burden in the blood and PLF. In high IL-6 responders, Meloxicam treatment was associated with reduced circulating IL-10 and IL-1ß compared to the Non-A septic group. In low IL-6 responders, Meloxicam increased circulating MCP-1 levels and decreased PGE2 levels compared to Non-A septic mice. Notably, Meloxicam reduced spleen neutrophil infiltration by 20% compared to two other sepsis groups. Conclusion: Metamizole and Meloxicam effectively relieved pain and increased the animals' basal activity in the PCI sepsis model. Meloxicam prolonged survival yet triggered maladaptive responses due to its immunosuppressive features that decreased tissue bacterial clearance during sepsis. In contrast, Metamizole constitutes a safe and effective non-opioid alternative for analgesic control in the non-surgical PCI sepsis model.


Asunto(s)
Dipirona , Modelos Animales de Enfermedad , Meloxicam , Ratones Endogámicos C57BL , Sepsis , Animales , Meloxicam/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Sepsis/mortalidad , Dipirona/uso terapéutico , Dipirona/farmacología , Ratones , Analgésicos/uso terapéutico , Analgésicos/farmacología , Inmunomodulación/efectos de los fármacos , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Masculino , Citocinas/metabolismo , Citocinas/sangre , Peritonitis/tratamiento farmacológico , Peritonitis/inmunología , Peritonitis/microbiología , Peritonitis/mortalidad , Humanos
5.
Sci Rep ; 14(1): 20519, 2024 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227626

RESUMEN

We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P < 0.001). The difference between the two groups was not significant for the concentrations of CRP, C1q and inflammatory cytokines on the thirtieth day of the trial. According to the second level of vitamin D, there was a 14.3% difference in positive infection rates between the vitamin D adequate (> 30 ng/mL) and deficient groups (< 20 ng/mL). Adequate vitamin D had a tendency to prevent COVID-19.Trial registration: ClinicalTrials.gov NCT05673980, dated: 12/2022.


Asunto(s)
Proteína C-Reactiva , COVID-19 , Citocinas , SARS-CoV-2 , Vitamina D , Humanos , Masculino , Vitamina D/sangre , Vitamina D/uso terapéutico , Vitamina D/análogos & derivados , Vitamina D/administración & dosificación , Femenino , COVID-19/prevención & control , COVID-19/sangre , COVID-19/epidemiología , Adulto , Persona de Mediana Edad , Citocinas/sangre , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Ergocalciferoles/uso terapéutico , Ergocalciferoles/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Complemento C1q/metabolismo
6.
FEMS Microbiol Lett ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271451

RESUMEN

In recent years, the emergence of multidrug-resistant bacteria has limited the selection of drugs for treating bacterial infections, reduced clinical efficacy, and increased treatment costs and mortality. It is urgent to find alternative antibiotics. In order to explore a new method for controlling methicillin resistant Staphylococcus aureus (S. aureus) , this study isolated and purified a multi drug resistant S. aureus broad-spectrum phage JPL-50 from wastewater. JPL-50 belongs to the Siphoviridae family after morphological observation, biological characterization, and transmission electron microscopy (TEM) fragmentation spectrum analysis. It can cleave 84% of tested S. aureus (168/200) , in which 100% of tested mastitis-associated strains (48/48) and 72.04% of MRSA strains (67/93) were lysed. In addition, it has an optimal growth temperature of about 30°C, a high activity within a wide pH range (pH 3-10) , and an optimal multiplicity of infection of 0.01. The one-step growth curve shows a latent time of 20 minutes, an explosive time of 80 minutes. JPL-50 was 16, 927 bp in length and was encoded by double-stranded DNA, with no genes associated with bacterial resistance or virulence factors detected. In a therapeutic study, injection of the phage JPL-50 once and for 7 times in 7 days protected 40% and 60% of the mice from fatal S.aureus infection, respectively. More importantly, JPL-50-doxycycline combination could effectively inhibit host S.aureus in vitro and reduce the use of doxycycline within 8 hours. In conclusion, the bacteriophage JPL-50 has a wide lysis spectrum, high lysis rate, high tolerance to extreme environments, and moderate in vivo activity, providing ideas for developing multidrug-resistant S. aureus infections.

7.
J Pharm Anal ; 14(8): 100968, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39258173

RESUMEN

There is increasing evidence that the activation of glucagon-like peptide-1 receptor (GLP-1R) can be used as a therapeutic intervention for cognitive disorders. Here, we have screened GLP-1R targeted compounds from Scutellaria baicalensis, which revealed baicalein is a potential GLP-1R small-molecule agonist. Mitophagy, a selective autophagy pathway for mitochondrial quality control, plays a neuroprotective role in multiple cognitive impairment diseases. We noticed that Glp1r knock-out (KO) mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze (MWM) test than their wide-type (WT) counterparts. Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice. Finally, we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner. Our findings shed light on the importance of GLP-1R for cognitive function maintenance, and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis. Furthermore, we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

8.
J Magn Reson Imaging ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39229904

RESUMEN

BACKGROUND: Pathophysiological mechanisms underlying cognitive impairment in end-stage renal disease (ESRD) remain unclear, with limited studies on the temporal variability of neural activity and its coupling with regional perfusion. PURPOSE: To assess neural activity and neurovascular coupling (NVC) in ESRD patients, evaluate the classification performance of these abnormalities, and explore their relationships with cognitive function. STUDY TYPE: Prospective. POPULATION: Exactly 33 ESRD patients and 35 age, sex, and education matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: The 3.0T/3D pseudo-continuous arterial spin labeling, resting-state functional MRI, and 3D-T1 weighted structural imaging. ASSESSMENT: Dynamic (dfALFF) and static (sfALFF) fractional amplitude of low-frequency fluctuations and cerebral blood flow (CBF) were assessed. CBF-fALFF correlation coefficients and CBF/fALFF ratio were determined for ESRD patients and HCs. Their ability to distinguish ESRD patients from HCs was evaluated, alongside assessment of cerebral small vessel disease (CSVD) MRI features. All participants underwent blood biochemical and neuropsychological tests to evaluate cognitive decline. STATISTICAL TESTS: Chi-squared test, two-sample t-test, Mann-Whitney U tests, covariance analysis, partial correlation analysis, family-wise error, false discovery rate, Bonferroni correction, area under the receiver operating characteristic curve (AUC) and multivariate pattern analysis. P < 0.05 denoted statistical significance. RESULTS: ESRD patients exhibited higher dfALFF in triangular part of left inferior frontal gyrus (IFGtriang) and left middle temporal gyrus, lower CBF/dfALFF ratio in multiple brain regions, and decreased CBF/sfALFF ratio in bilateral superior temporal gyrus (STG). Compared with CBF/sfALFF ratio, dfALFF, and sfALFF, CBF/dfALFF ratio (AUC = 0.916) achieved the most powerful classification performance in distinguishing ESRD patients from HCs. In ESRD patients, decreased CBF/fALFF ratio correlated with more severe renal impairment, increased CSVD burden, and cognitive decline (0.4 < |r| < 0.6). DATA CONCLUSION: ESRD patients exhibited abnormal dynamic brain activity and impaired NVC, with dynamic features demonstrating superior discriminative capacity and CBF/dfALFF ratio showing powerful classification performance. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

9.
Int J Mol Sci ; 25(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39201557

RESUMEN

Biofertilizers are environmentally friendly compounds that can enhance plant growth and substitute for chemically synthesized products. In this research, a new strain of the bacterium Bacillus velezensis, designated JZ, was isolated from the roots of strawberry plants and exhibited potent antagonistic properties against Bacillus altitudinis m-1, a pathogen responsible for leaf spot disease in strawberry. The fermentation broth of JZ exerted an inhibition rate of 47.43% against this pathogen. Using an optimized acid precipitation method, crude extracts of lipopeptides from the JZ fermentation broth were obtained. The crude extract of B. velezensis JZ fermentation broth did not significantly disrupt the cell permeability of B. altitudinis m-1, whereas it notably reduced the Ca2+-ATPase activity on the cell membrane and markedly elevated the intracellular reactive oxygen species (ROS) concentration. To identify the active compounds within the crude extract, QTOF-MS/MS was employed, revealing four antimicrobial compounds: fengycin, iturin, surfactin, and a polyene antibiotic known as bacillaene. The strain JZ also produced various plant-growth-promoting substances, such as protease, IAA, and siderophore, which assists plants to survive under pathogen infection. These findings suggest that the JZ strain holds significant potential as a biological control agent against B. altitudinis, providing a promising avenue for the management of plant bacterial disease.


Asunto(s)
Bacillus , Fragaria , Enfermedades de las Plantas , Bacillus/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Fragaria/microbiología , Hojas de la Planta/microbiología , Especies Reactivas de Oxígeno/metabolismo , Lipopéptidos/farmacología , Lipopéptidos/metabolismo , Agentes de Control Biológico/farmacología , Antibiosis
10.
Front Nutr ; 11: 1351503, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193561

RESUMEN

Background: Protein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients. Methods: The novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility. Results: From September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741-0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05). Conclusion: Our results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.

11.
Sci Rep ; 14(1): 19883, 2024 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191842

RESUMEN

Muscle quality index (MQI) is a novel indicator reflecting the quality of skeletal muscles. The association between MQI and the development of advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is unknown. We investigated the association of low MQI with advanced fibrosis among adults with NAFLD using a nationally representative sample of the US population. Adults with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included. Sex-specific standard was used to define low and extremely low MQI. Univariate and multivariate logistic regressions were used to assess the association between MQI level and advanced fibrosis. In the study, 3758 participants with NAFLD were included. The prevalence of low and extremely low MQI was 11.7% (95% CI 10.4-13.0%) and 2.2% (95% CI 1.6-2.8%), respectively. Among these participants, 96 were assessed to have advanced fibrosis. Individuals with low [(odds ratio (OR) 2.45, 95% confidence interval (CI) 1.22-4.91)] and extremely low MQI (OR 10.48, 95% CI 3.20-34.27) were associated with advanced fibrosis in multivariable analysis. A linear trend relationship was also observed between MQI level and the risk of advanced fibrosis (Ptrend = 0.001). Subgroup and sensitivity analyses yielded similar results to the main analyses. Decreased MQI is highly prevalent, and is associated with an increased risk of advanced fibrosis in adult US population with NAFLD.


Asunto(s)
Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Músculo Esquelético/patología , Factores de Riesgo , Estados Unidos/epidemiología , Prevalencia , Estudios Transversales
12.
China CDC Wkly ; 6(30): 727-733, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39114316

RESUMEN

Introduction: This study analyzed long-term trends in the incidence of acute hepatitis B (AHB) in China, focusing on age, period, and cohort effects on incidence. Methods: Data on AHB from 2005 to 2021 were extracted from the National Notifiable Disease Reporting System (NNDRS) of China for analysis. Incidences of AHB were calculated by gender and age group using population denominators from the 2000, 2010, and 2020 censuses. Joinpoint regression was employed to evaluate trends, and an age-period-cohort model was used to assess the age, period, and cohort effects. Results: The annual average incidence of reported AHB in children aged 14 years and below in low, intermediate, and high endemic areas decreased from 1.65, 2.33, and 2.56 per 100,000 in 2005-2010 to 0.56, 0.58, and 0.48 per 100,000 in the 2016-2021 period. The 15-39-year age group in high endemic areas exhibited the most significant decline in incidence, dropping from 23.14 per 100,000 in 2005 to 4.59 per 100,000 in 2021 among males and from 10.62 per 100,000 to 3.21 per 100,000 among females. Age-period-cohort analysis indicated decreasing age, period, and cohort effects for reported AHB incidence in each endemic area, except for a slight upward trend in the 15-19-year age group and in the cohort born between 1951 and 1955. Conclusions: This study demonstrated a rapid decline in AHB incidence across various endemic areas since 2005. Children aged 14 years and below exhibited very low AHB incidences, while the incidence among individuals over 15 years was higher. To further reduce AHB incidence, hepatitis B vaccine (HepB) coverage should be enhanced among adolescents and adults.

13.
Chem Sci ; 15(31): 12480-12487, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39118633

RESUMEN

Porous materials have attracted interest due to their high specific surface area and rich functionality. Immobilizing organocatalysts onto porous polymers not only boosts enantioselectivity but also improves the reaction rates. In this work, a series of porous polymers C-poly-3ms with rigid polyisocyanide-carrying secondary amine pendants as building blocks were successfully prepared. And the pore size and optical activity of C-poly-3ms can be controlled by the length of the polyisocyanide blocks due to their rigid and helical backbone. C-poly-3150 demonstrated a preferred left-handed helix with a θ 364 value of -8.21 × 103. The pore size and S BET of C-poly-3150 were 17.52 nm and 7.98 m2 g-1, respectively. The porous C-poly-3150 catalyzes the asymmetric Michael addition reaction efficiently and generates the target products in satisfactory yield and excellent enantioselectivity. For 6ab, an enantiomeric excess (ee) and a diastereomeric ratio (dr) up to 99% and 99/1 could be achieved, respectively. The recovered catalyst can be recycled at least 6 times in the asymmetric Michael addition reaction while maintaining activity and stereoselectivity.

14.
Curr Med Chem ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39129288

RESUMEN

BACKGROUND: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14ß-hydroxy- 3ß-(ß-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms. METHODS: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed. RESULTS: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis. CONCLUSION: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC.

15.
ACS Appl Mater Interfaces ; 16(35): 46495-46505, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39167418

RESUMEN

Investigating organic carriers' utilization efficiency and bioactivity within organic-inorganic hybrid nanoflowers is critical to constructing sensitive immunosensors. Nevertheless, the sensitivity of immunosensors is interactively regulated by different classes of biomolecules such as antibodies and enzymes. In this work, we introduced a new alkaline phosphatase-antibody-CaHPO4 hybrid nanoflowers (AAHNFs) microreactor based colorimetric immunoprobe. This system integrates a biometric unit (antibody) with a signal amplification element (enzyme) through the biomineralization process. Specifically, the critical factors affecting antibody recognition activity in the formation mechanism of AAHNFs are investigated. The designed AAHNFs retain antibody recognition ability with enhanced protection for encapsulated proteins against high temperature, organic solvents, and long-term storage, facilitating the selective construction of lock structures against antigens. Additionally, a colorimetric immunosensor based on AAHNFs was developed. After ascorbic acid 2-phosphate hydrolysis by alkaline phosphatase (ALP), the generated ascorbic acid decomposes I2 to I-, inducing the localized surface plasmon resonance in the silver nanoplate, which is effectively tuned through shape conversion to develop the sensor. Further, a 3D-printed portable device is fabricated, integrated with a smartphone sensing platform, and applied to the data of collection and analysis. Notably, the immunosensor exhibits improved analytical performance with a 0.1-6.25 ng·mL-1 detection range and a 0.06 ng·mL-1 detection limit for quantitative saxitoxin (STX) analysis. The average recoveries of STX in real samples ranged from 85.9% to 105.9%. This study presents a more in-depth investigation of the recognition element performance, providing insights for improved antibody performance in practical applications.


Asunto(s)
Fosfatasa Alcalina , Colorimetría , Saxitoxina , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/química , Saxitoxina/análisis , Saxitoxina/química , Colorimetría/métodos , Técnicas Biosensibles/métodos , Biocatálisis , Límite de Detección , Nanoestructuras/química , Inmunoensayo/métodos , Ácido Ascórbico/química , Ácido Ascórbico/análisis , Ácido Ascórbico/análogos & derivados , Plata/química
16.
Eur J Med Chem ; 277: 116772, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39167895

RESUMEN

In addressing the urgent need for novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) to combat drug resistance, we employed CuAAC click chemistry to construct a diverse 312-member diarylpyrimidine (DAPY) derivative library. This rapid synthesis approach facilitated the identification of A6N36, demonstrating exceptional HIV-1 RT inhibitory activity. Moreover, it was demonstrated with EC50 values of 1.8-8.7 nM for mutant strains L100I, K103 N, Y181C, and E138K, being equipotent or superior to that of ETR. However, A6N36's efficacy was compromised against specific resistant strains (Y188L, F227L + V106A and RES056), highlighting a need for further optimization. Through scaffold hopping, we optimized this lead to develop 10c, which exhibited broad-spectrum activity with EC50 values ranging from 3.2 to 57.5 nM and superior water solubility. Molecular docking underscored the key interactions of 10c within the NNIBP. Our findings present 10c as a promising NNRTI lead, illustrating the power of click chemistry and rational design in combatting HIV-1 resistance.


Asunto(s)
Fármacos Anti-VIH , Química Clic , Transcriptasa Inversa del VIH , VIH-1 , Inhibidores de la Transcriptasa Inversa , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/síntesis química , VIH-1/efectos de los fármacos , VIH-1/enzimología , Relación Estructura-Actividad , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Estructura Molecular , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Descubrimiento de Drogas , Cobre/química , Cobre/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos
17.
J Photochem Photobiol B ; 258: 112998, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39096719

RESUMEN

Depression, a multifactorial mental disorder, characterized by cognitive slowing, anxiety, and impaired cognitive function, imposes a significant burden on public health. Photobiomodulation (PBM), involving exposure to sunlight or artificial light at a specific intensity and wavelength for a determined duration, influences brain activity, functional connectivity, and plasticity. It is recognized for its therapeutic efficacy in treating depression, yet its molecular and cellular underpinnings remain obscure. Here, we investigated the impact of PBM with 468 nm light on depression-like behavior and neuronal damage in the chronic unpredictable mild stress (CUMS) murine model, a commonly employed animal model for studying depression. Our results demonstrate that PBM treatment ameliorated behavioral deficits, inhibited neuroinflammation and apoptosis, and notably rejuvenates the hippocampal synaptic function in depressed mice, which may be mainly attributed to the up-regulation of brain-derived neurotrophic factor signaling pathways. In addition, in vitro experiments with a corticosterone-induced hippocampal neuron injury model demonstrate reduced oxidative stress and improved mitochondrial function, further validating the therapeutic potential of PBM. In summary, these findings suggest PBM as a promising, non-invasive treatment for depression, offering insights into its biological mechanisms and potential for clinical application.


Asunto(s)
Depresión , Modelos Animales de Enfermedad , Hipocampo , Terapia por Luz de Baja Intensidad , Mitocondrias , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Ratones , Depresión/metabolismo , Depresión/terapia , Hipocampo/efectos de la radiación , Hipocampo/metabolismo , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Sinapsis/efectos de la radiación , Sinapsis/metabolismo , Estrés Oxidativo/efectos de la radiación , Ratones Endogámicos C57BL , Neuronas/efectos de la radiación , Neuronas/metabolismo , Plasticidad Neuronal/efectos de la radiación , Corticosterona , Conducta Animal/efectos de la radiación , Apoptosis/efectos de la radiación , Estrés Psicológico
18.
ACS Nano ; 18(33): 22431-22443, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39103298

RESUMEN

Osteoclastic inhibition using antiresorptive bisphosphonates and osteogenic promotion using antisclerostin agents represent two distinct osteoporosis treatments in clinical practice, each individual treatment suffers from unsatisfactory therapeutic efficacy due to its indirect intervention in osteoclasis and promotion of osteogenesis simultaneously. Although this issue is anticipated to be resolved by drug synergism, a tempting carrier-free dual-medication nanoassembly remains elusive. Herein, we prepare such a nanoassembly made of antiresorptive alendronate (ALN) crystal and antisclerostin polyaptamer (Apt) via a nucleic acid-driven crystallization method. This nanoparticle can protect Apt from rapid nuclease degradation, avoid the high cytotoxicity of free ALN, and effectively concentrate in the cancellous bone by virtue of the bone-binding ability of DNA and ALN. More importantly, the acid microenvironment of cancellous bone triggers the disassociation of nanoparticles for sustained drug release, from which ALN inhibits the osteoclast-mediated bone resorption while Apt promotes osteogenic differentiation. Our work represents a pioneering demonstration of nucleic acid-driven crystallization of a bisphosphonate into a tempting carrier-free dual-medication nanoassembly. This inaugural advancement augments the antiosteoporosis efficacy through direct inhibition of osteoclasis and promotion of osteogenesis simultaneously and establishes a paradigm for profound understanding of the underlying synergistic antiosteoporosis mechanism of antiresorptive and antisclerostin components. It is envisioned that this study provides a highly generalizable strategy applicable to the tailoring of a diverse array of DNA-inorganic nanocomposites for targeted regulation of intricate pathological niches.


Asunto(s)
Alendronato , Cristalización , Osteoclastos , Osteogénesis , Osteoporosis , Alendronato/química , Alendronato/farmacología , Osteogénesis/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoporosis/tratamiento farmacológico , Animales , Ratones , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/química , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Células RAW 264.7 , Humanos , Sinergismo Farmacológico
19.
Sci Total Environ ; 950: 175338, 2024 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-39117206

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are potent inhibitors of DNA that can induce genetic damage, abnormal gene expression, and metabolic disorders upon interfacing with biological macromolecules. However, the mechanism of their interactions with DNA remains elusive. Therefore, this study selected three representative PAHs, including phenanthrene (Phen), pyrene (Pyre), and benzo[a]pyrene (B[a]P), and explored their binding mechanisms with the double-strand DNA (dsDNA) from different species, including 1J1V (Escherichia coli), 6J5B (Arabidopsis thaliana), and 6Q1V (Homo sapiens). The results revealed that binding between PAHs and dsDNA occurred in the groove via van der Waals forces and π-π stacking, with the carboxyl oxygen atom of the thymine (T)-base within dsDNA being the key binding site. This result was further confirmed by the spectroscopic experiments, where significant changes in the peak of the T-base were observed after PAHs-dsDNA binding. More interestingly, the total binding energies of Pyre with the three dsDNA were -138.800 kJ/mol (Pyre-1J1V), -105.523 kJ/mol (Pyre-6J5B), and -127.567 kJ/mol (Pyre-6Q1V), respectively, all of which were higher than those of Phen and B[a]P. This suggests that that Pyre has the strongest dsDNA binding ability. Additionally, analysis of the thermodynamic parameters indicated that the interactions between the three PAHs and dsDNA were exothermic reactions. In contrast, the Pyre-dsDNA interaction predominantly involved van der Waals forces and hydrogen bonding due to the enthalpy change (∆H) < 0 and entropy change (∆S) < 0, while the Phen-dsDNA and B[a]P-dsDNA interactions predominantly involved hydrophobic forces due to ∆H > 0 and ∆S > 0. Furthermore, Pyre caused local distortion of dsDNA, which was more pronounced under atomic force microscopy (AFM). In summary, this study has unveiled a new phenomenon of binding between PAHs and dsDNA. This sheds light on the carcinogenic potential and environmental impacts of PAHs pollution.


Asunto(s)
ADN , Hidrocarburos Policíclicos Aromáticos , Timina , Timina/química , Humanos , Arabidopsis/metabolismo , Escherichia coli , Fenantrenos , Pirenos/química
20.
Psychiatry Res Neuroimaging ; 343: 111866, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39098261

RESUMEN

The involvement of the right hemisphere, mainly the activation of the right cerebral regions, in recovery from post-stroke aphasia has been widely recognized. In contrast, the role of the right white matter pathways in the recovery from post-stroke aphasia is rarely understood. In this study, we aimed to provide a primary overview of the correlation between the structural integrity of the right hemispheric neural tracts based on the dual-stream model of language organization and recovery from post-stroke aphasia by systematically reviewing prior longitudinal interventional studies. By searching electronic databases for relevant studies according to a standard protocol, a total of 10 records (seven group studies and three case studies) including 79 participants were finally included. After comprehensively analyzing these studies and reviewing the literature, although no definite correlation was found between the right hemispheric neural tracts and recovery from post-stroke aphasia, our review provideds a new perspective for investigating the linguistic role of the right hemispheric neural tracts. This suggests that the involvement of the right hemispheric neural tracts in recovery from post-stroke aphasia may be mediated by multiple factors; thus, this topic should be comprehensively investigated in the future.


Asunto(s)
Afasia , Lenguaje , Recuperación de la Función , Accidente Cerebrovascular , Humanos , Afasia/etiología , Afasia/fisiopatología , Afasia/rehabilitación , Accidente Cerebrovascular/complicaciones , Recuperación de la Función/fisiología , Vías Nerviosas/fisiopatología , Lateralidad Funcional/fisiología , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen
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