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1.
Sci Rep ; 14(1): 23656, 2024 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-39390073

RESUMEN

A copper-based metal-organic framework named NH2-Cu-MOF has been synthesized and utilized as an effective broad-spectrum antimicrobial material in this article. The obtained NH2-Cu-MOF exhibits satisfying antibacterial activity against both gram-positive bacteria (S. aureus and S. epidermidis) and gram-negative bacteria (E. coli and K. peneumoniae). Additionally, the biocompatibility of this NH2-Cu-MOF has been validated through animal studies, showing no significant adverse effects, thereby confirming its high biocompatibility. These findings prove that NH2-Cu-MOF has positive effects upon the treatment of bacteria-infected wounds, which holds great potential to be applied in biochemistry field.


Asunto(s)
Antibacterianos , Cobre , Estructuras Metalorgánicas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Cobre/química , Cobre/farmacología , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Animales , Bacterias Gramnegativas/efectos de los fármacos , Ratones
2.
Adv Funct Mater ; 34(33)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39399303

RESUMEN

Stretchable electrodes are an essential component in soft actuator systems. In particular, Joule heating electrodes (JHEs) are required for thermal actuation systems. A highly stretchable, patternable, and low-voltage operating JHE based on hybrid layers of silver nanowires (AgNWs) and carbon nanotubes (CNTs) is reported. The conductive layers were applied on a locally pre-strained bistable electroactive polymer (BSEP) membrane to form a wrinkled conductive surface with a low resistance of 300 Ω/sq, and subsequently patterned to a serpentine trace by laser engraving. The resistance of the resulting electrode remains nearly unchanged up to ~80-90% area strain. By applying a voltage of 7 - 9 V to the electrode, the temperature of the BSEP membrane increased to more than 60 °C, well above the polymer's phase transition temperature of 46 °C, thereby lowering its modulus by a factor of 103. An electronic Braille device based on the JHEs on a BSEP membrane was assembled with a diaphragm chamber. The electrode was patterned into 3 × 2 individually addressable pixels according to the standard U.S. Braille cell format. Through Joule heating of the pixels and local expansion of the BSEP membrane using a small pneumatic pressure, the pixels deformed out of the plane by over 0.5 mm to display specific Braille letters. The Braille content can be refreshed for 20,000 cycles at the same operating voltage.

3.
Mikrochim Acta ; 191(11): 679, 2024 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-39422792

RESUMEN

A simple one-pot green synthesis method was used to prepare urease-inorganic hybrid nanoflowers (UE-HNFs), which had a high surface-to-volume ratio to improve enzyme catalytic efficiency and make urease reusable. A portable colorimetric microliter tube based on urease-inorganic hybrid nanoflowers (UE-HNFs-PCMT), as an urea colorimetric biosensor, was developed for determining urea concentration in milk. The combination of urea colorimetric biosensor and a smartphone is used for capturing the colour change of milk after reaction. There was a good linear relationship between colour intensity of the image (Δ intensity) and urea concentration (43-600 mg L-1), with a detection limit of 12.81 mg L-1. UE-HNFs-PCMT has the advantages of no need for complex equipment, easy operation, reusability, low detection cost, good portability, and environmental friendliness and can achieve urea detection in milk.


Asunto(s)
Técnicas Biosensibles , Colorimetría , Límite de Detección , Leche , Nanoestructuras , Urea , Ureasa , Ureasa/química , Urea/análisis , Urea/química , Leche/química , Colorimetría/métodos , Animales , Técnicas Biosensibles/métodos , Nanoestructuras/química , Enzimas Inmovilizadas/química , Teléfono Inteligente
4.
Food Chem X ; 23: 101756, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39295963

RESUMEN

Studies have demonstrated the protective effect of milk fat globule membrane (MFGM) on probiotics in harsh environments. However, currently, there are no reports on the encapsulation of probiotics using MFGM. In this study, MFGM and pullulan (PUL) polysaccharide fibers were prepared by electrostatic spinning and used to encapsulate probiotics, with whey protein isolates (WPI)/PUL as the control. The morphology, physical properties, mechanical properties, survival, and stability of the encapsulated Lacticaseibacillus rhamnosus GG (LGG) were studied. The results showed that the MFGM/PUL solution had significant effects on pH, viscosity, conductivity, and stability. Electrostatic spinning improved the mechanical properties and encapsulation ability of the polymer formed by MFGM/PUL. LGG encapsulated in MFGM/PUL nanofibers survived rate was higher than WPI/PUL nanofibers in mimic intestinal juice, which could be attributed to the phospholipid content contained in MFGM. These results demonstrate that MFGM is a promising material for probiotic encapsulation, providing an important basis for the potential use of MFGM/PUL nanofibers as a robust encapsulation matrix.

5.
Lipids Health Dis ; 23(1): 240, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107777

RESUMEN

OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.


Asunto(s)
HDL-Colesterol , LDL-Colesterol , Colesterol , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Colesterol/sangre , Dilatación Patológica/sangre , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anciano , LDL-Colesterol/sangre , Vasos Coronarios/patología , Vasos Coronarios/diagnóstico por imagen , HDL-Colesterol/sangre , Factores de Riesgo , Triglicéridos/sangre , Oportunidad Relativa
6.
Curr Vasc Pharmacol ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39069811

RESUMEN

BACKGROUND: Myocardial metabolism is closely related to functional changes after myocardial infarction (MI). OBJECTIVE: This study aimed to present an integrative examination of human ischemic cardiomyopathy. METHODS: We used both GSE121893 single-cell suspension sequencing and GSE19303 transcription microarray data sets from the GEO database, along with a murine MI model for full-spectrum metabolite detection. Through a systematic investigation that involved differential metabolite identification and functional enrichment analysis, we shed light on the pivotal role of energy metabolism dysregulation in the progression of MI. RESULTS: Our findings revealed an association between the core regulatory genes CDKN1A, FOS, ITGB4, and MAP2K1 and the underlying pathophysiology of the disease. These genes are identified as critical elements in the complex landscape of myocardial ischemic disorder, highlighting novel insights into therapeutic targets and the intricate biological mechanisms involved. CONCLUSION: This analysis provides a framework for future research on the metabolic alterations associated with MI.

7.
Int J Biol Macromol ; 277(Pt 1): 134010, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39032891

RESUMEN

Capsular polysaccharide (CPS) as a probiotic component has the ability to regulate the function of the host's immune system. However, how the structure and function of heat-killed CPS are altered remains unclear. In the present study, CPS were isolated and purified from live (LCPS) and heat-killed (HCPS) Lacticaseibacillus paracasei 6235. The differences in structure and immunomodulation between LCPS and HCPS were compared and analyzed. The results demonstrate that after heat killed, the molecular weight of CPS decreased from 23.4 kDa to 17.5 kDa, with the disappearance of galactosamine in the monosaccharide composition, and changes in the microstructure. Methylation analysis and nuclear magnetic resonance analysis revealed that the LCPS and HCPS are similar in structure, which main units of →3,4)-α-D-Glcp-(1→4)-α-D-Galp-(1→3)-ß-L-Rhap-(1→6)-ß-D-Galp-(1→, and repeating units of →3,4)-α-D-Glcp-(1→, →3)-ß-L-Rhap-(1→, and →4)-α-D-Galp-(1→ residues. Furthermore, both LCPS and HCPS significantly downregulated the expression of pro-inflammatory cytokines in RAW264.7 cells induced by LPS. Specifically, HCPS reduced the levels of IL-6 and IL-1ß by 79.38 % and 88.42 %, respectively, compared to LCPS. Concurrently, both LCPS and HCPS effectively mitigated inflammatory responses through the NF-κB and MAPK signaling pathways. Moreover, compared to LCPS, HCPS increased the protein expression levels of NF-κB/p-NF-κB and IκB/p-IκB by 26.14 % and 28.92 %, respectively. These results suggest that CPS has a role in modulating immune responses and that HCPS is more effective. This study can be further developed into new products related to postbiotics.


Asunto(s)
Calor , Lacticaseibacillus paracasei , Polisacáridos Bacterianos , Ratones , Animales , Células RAW 264.7 , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/farmacología , Lacticaseibacillus paracasei/química , Peso Molecular , FN-kappa B/metabolismo , Cápsulas Bacterianas/química , Cápsulas Bacterianas/inmunología , Interleucina-6/metabolismo , Citocinas/metabolismo , Metilación
8.
World J Gastroenterol ; 30(19): 2505-2511, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38817656

RESUMEN

Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.


Asunto(s)
Dinoprostona , Mucosa Intestinal , Transportadores de Anión Orgánico , Humanos , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Enfermedad Crónica , Dinoprostona/metabolismo , Intestino Delgado/patología , Intestino Delgado/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedades Intestinales/genética , Enfermedades Intestinales/patología , Animales , Hemorragia Gastrointestinal/genética , Hemorragia Gastrointestinal/etiología , Úlcera/genética , Úlcera/patología
9.
Small ; 20(33): e2311914, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38566542

RESUMEN

The high-performance hole transporting material (HTM) is one of the most important components for the perovskite solar cells (PSCs) in promoting power conversion efficiency (PCE). However, the low conductivity of HTMs and their additional requirements for doping and post-oxidation greatly limits the device performance. In this work, three novel pyrene-based derivatives containing methoxy-substituted triphenylamines units (PyTPA, PyTPA-OH and PyTPA-2OH) are designed and synthesized, where different numbers of hydroxyl groups are connected at the 2- or 2,7-positions of the pyrene core. These hydroxyl groups at the 2- or 2,7-positions of pyrene play a significantly role to enhance the intermolecular interactions that are able to generate in situ radicals with the assistance of visible light irradiation, resulting in enhanced hole transferring ability, as well as an enhanced conductivity and suppressed recombination. These pyrene-core based HTMs exhibit excellent performance in PSCs, which possess a higher PCE than those control devices using the traditional spiro-OMeTAD as the HTM. The best performance can be found in the devices with PyTPA-2OH. It has an average PCE of 23.44% (PCEmax = 23.50%), which is the highest PCE among the reported PSCs with the pyrene-core based HTMs up to date. This research offers a novel avenue to design a dopant-free HTM by the combination of the pyrene core, methoxy triphenylamines, and hydroxy groups.

10.
J Psychiatr Res ; 172: 244-253, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38412787

RESUMEN

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.


Asunto(s)
Trastorno Depresivo Mayor , Reflujo Gastroesofágico , Trastornos Mentales , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/genética , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/genética , Estudio de Asociación del Genoma Completo
11.
J Org Chem ; 89(5): 3319-3330, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38362859

RESUMEN

High-efficiency narrow-band luminescent materials have attracted intense interest, resulting in their great colorimetric purity. This has led to a variety of high-tech applications in high-definition displays, spectral analysis, and biomedicine. In this study, a rigid pyrene core was employed as the molecular backbone, and four narrow-band pyrene-based blue emitters were synthesized using various synthetic methods (such as Lewis-acid catalyzed cyclization domino reactions, Pd-catalyzed coupling reactions like Suzuki-Miyaura and Sonogashira). Due to the steric effect of the hydroxy group at the 2-position, the target compounds exhibit deep blue emission (<429 nm, CIEy < 0.08) with full width at half-maximum (FWHM) less than 33 nm both in solution and when solidified. The experimental and theoretical results indicated that the substituents at the 1- and 3-positions afford a large dihedral angle with the pyrene core, and the molecular motion is almost fixed by multiple intra- and intermolecular hydrogen bonding interactions in the crystallized state, leading to a suppression of the vibrational relaxation of the molecular structure. Moreover, we observed that the suppression of the vibrational relaxation in the molecular structures and the construction of rigid conjugated structures can help develop narrow-band organic light-emitting materials.

12.
J Cancer ; 15(5): 1414-1428, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38356721

RESUMEN

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

13.
J Org Chem ; 89(3): 1681-1691, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38207100

RESUMEN

Pyrene-based derivatives have been widely deployed in organic luminescent materials because of their bright fluorescence, high charge carrier mobility, and facile modification. Nevertheless, the fluorescence output of conventional pyrenes is prone to quenching upon aggregation due to extensive intermolecular π-π stacking interactions. To address this issue, a set of new Y-shaped pyrene-containing luminogens are synthesized from a new bromopyrene chemical precursor, 2-hydroxyl-7-tert-butyl-1,3-bromopyrene, where the bromo and hydroxyl groups at the pyrene core can be readily modified to obtain the target products and provide great flexibility in tuning the photophysical performances. When the hydroxy group at the 2-position of pyrene was replaced by a benzyl group, the steric hindrance of the benzyl group not only efficiently inhibits the detrimental intermolecular π-π stacking interactions but also rigidifies the molecular conformation, resulting in a narrow-band blue emission. Moreover, the TPE-containing compounds 2c and 3c possessed characteristic aggregation-induced emission (AIE) properties with fluorescence quantum yields of up to 66% and 38% in the solid state, respectively. Thus, this article has methodically investigated the factors influencing the optical behavior, such as intermolecular interactions, and the steric effects of the substituent group, thereby opening up the potential to develop narrow-band pyrene-based blue emitters for OLED device applications.

14.
Foods ; 13(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38201190

RESUMEN

Porcine intestinal mucosal proteins are novel animal proteins that contain large amounts of free amino acids and peptides. Although porcine intestinal mucosal proteins are widely used in animal nutrition, the peptide bioactivities of their enzymatic products are not yet fully understood. In the present study, we investigated the effect of porcine intestinal mucosal peptides (PIMP) on the RAW264.7 cell model of LPS-induced inflammation. The mRNA expression of inflammatory factors (interleukin 6, tumor necrosis factor-α, and interleukin-1ß) and nitrous oxide levels were all measured by quantitative real-time PCR and cyclooxygenase-2 protein expression measured by Western blot. To investigate the modulating effect of PIMP and to establish a model of dextran sodium sulfate (DSS)-induced colitis in mice, we examined the effects of hematoxylin-eosin staining, myeloperoxidase levels, pro-inflammatory factor mRNA content, tight junction protein expression, and changes in intestinal flora. Nuclear factor κB pathway protein levels were also assessed by Western blot. PIMP has been shown in vitro to control inflammatory responses and prevent the activation of key associated signaling pathways. PIMP at doses of 100 and 400 mg/kg/day also alleviated intestinal inflammatory responses, reduced tissue damage caused by DSS, and improved intestinal barrier function. In addition, PIMP at 400 mg/kg/day successfully repaired the dysregulated gut microbiota and increased short-chain fatty acid levels. These findings suggest that PIMP may positively influence inflammatory responses and alleviate colitis. This study is the first to demonstrate the potential of PIMP as a functional food for the prevention and treatment of colitis.

15.
Luminescence ; 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053240

RESUMEN

Three new pyrrolo[3,2-b]pyrrole derivatives containing methoxyphenyl, pyrene or tetraphenylethylene (TPE) units (compounds 1-3) have been designed, synthesized and fully characterized. The aggregation-induced emission (AIE) properties of compounds 1-3 were tested in different water fraction (fw ) of tetrahydrofuran (THF). The pyrrolo[3,2-b]pyrrole derivative 3 containing TPE units exhibited typical AIE features with an enhanced emission (∼32-fold) in the solid state versus in solution; compounds 1 and 2 exhibited an aggregation-caused quenching effect. In addition, the steric and electronic effects of the peripheral moieties on the emission behavior, both in solution and in the solid state, have been investigated. Moreover, pyrrolo[3,2-b]pyrrole 1 exhibits high sensitivity and selectivity for dichloromethane and chloroform solvents, with the system displaying a new emission peak and fast response time under ultraviolet irradiation.

16.
ACS Appl Mater Interfaces ; 15(51): 59787-59794, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38097388

RESUMEN

Electrophysiological (EP) signals, referred to as low-level biopotentials driven by active or passive human movements, are of great importance for kinesiology, rehabilitation, and human-machine interaction. To capture high-fidelity EP signals, bioelectrodes should possess high conductivity, high stretchability, and high conformability to skin. While traditional metal bioelectrodes are endowed with stretchability via complex structural designs, they are vulnerable to external or internal inference due to their low fracture strain and large modulus. Here, we report a self-healing elastic composite of silver nanowire (AgNW), graphite nanosheet, and styrene-block-poly(ethylene-ran-butylene)-block-polystyrene, which exhibits high stretchability of ε = 500%, high conductivity of σ = ∼1923 S·cm-1, and low resistance change (ΔR/R0) of 0.14 at ε = 40% while its resistance increases ∼0.8% after a 24 h stretching operation at ε = 50%. We employed the elastic composites for accurate and stable monitoring of electrocardiograph and surface electromyography (sEMG) signals. Further, we demonstrate an all-solution and printable process to obtain a large-scale sEMG bioelectrode array, enabling highly conformal adhesion on skin and high-fidelity gesture recognition.


Asunto(s)
Nanocables , Humanos , Nanocables/química , Gestos , Plata/química , Epidermis , Electrofisiología
17.
Brain Behav ; 13(11): e3225, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37654024

RESUMEN

BACKGROUND: Parkinson's disease (PD) is a common degenerative nervous system disease. At present, there are certain limitations in various treatment options aimed at preventing or delaying the progression of PD. Therefore, the exploration of new drugs for PD is beneficial. Mendelian randomization (MR) analysis can be used to explore the association between drugs and diseases. In this study, MR analysis was adopted to investigate the causal relationship between 23 drugs and PD. These drugs have been approved for the treatment of different diseases, such as salicylic acid and derivatives (collectively called salicylates, e.g., aspirin, used for fever and pain relief), antithrombotic agents (e.g., warfarin, aspirin, used for preventing thrombotic events). METHODS: The GWAS data for the 23 drugs were obtained from the UK Biobank (UKB) project, while the GWAS data for PD were sourced from FinnGen. Single-Nucleotide Polymorphisms (SNPs) were selected as instrumental variables (IVs). We first performed a series of quality control steps (including MR-PRESSO) to select the appropriate SNPs. Two-sample MR analysis was performed using five different methods, including inverse variance weighting (IVW) with random-effects model, weighted median, MR-Egger, simple model, and weighted model. At the same time, sensitivity analysis was carried out using the MR-Egger and Cochran's Q test to ensure the authenticity and reliability of the results. RESULTS: In MR-PRESSO, salicylates and antithrombotic agents showed statistically significant associations with PD, respectively. In the main MR analysis (IVW), there was a negative causal relationship between salicylates and PD (OR = 0.73, 95% CI = 0.54-0.98, p = .039). Similarly, there was a negative causal relationship between antithrombotic agents and PD (OR = 0.70, 95%CI = 0.52-0.96, p = .027). No statistically significant association was found between the remaining 21 drugs and PD. CONCLUSION: This MR study demonstrated that salicylates and antithrombotic agents can reduce the risk of PD, thus providing a novel avenue for future drug exploration in PD.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Fibrinolíticos , Análisis de la Aleatorización Mendeliana , Reproducibilidad de los Resultados , Aspirina/efectos adversos , Ácido Salicílico , Estudio de Asociación del Genoma Completo
18.
Nutrients ; 15(7)2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37049598

RESUMEN

Intestinal epithelial barrier function is closely associated with the development of many intestinal diseases. Heat-killed Lacticaseibacillus paracasei (HK-LP) has been shown to improve intestinal health and enhance immunity. However, the function of HK-LP in the intestinal barrier is still unclear. This study characterized the inflammatory effects of seven HK-LP (1 µg/mL) on the intestinal barrier using lipopolysaccharide (LPS) (100 µg/mL)-induced Caco-2 cells. In this study, HK-LP 6105, 6115, and 6235 were selected, and their effects on the modulation of inflammatory factors and tight junction protein expression (claudin-1, zona occludens-1, and occludin) were compared. The effect of different cultivation times (18 and 48 h) was investigated in response to LPS-induced intestinal epithelial barrier dysfunction. Our results showed that HK-LP 6105, 6115, and 6235 improved LPS-induced intestinal barrier permeability reduction and transepithelial resistance. Furthermore, HK-LP 6105, 6115, and 6235 inhibited the pro-inflammatory factors (TNF-α, IL-1ß, IL-6) and increased the expression of the anti-inflammatory factors (IL-4, IL-10, and TGF-ß). HK-LP 6105, 6115, and 6235 ameliorated the inflammatory response. It inhibited the nuclear factor kappa B (NF-κB) signaling pathway-mediated myosin light chain (MLC)/MLC kinase signaling pathway by downregulating the Toll-like receptor 4 (TLR4)/NF-κB pathway. Thus, the results suggest that HK-LP 6150, 6115, and 6235 may improve intestinal health by regulating inflammation and TJ proteins. Postbiotics produced by these strains exhibit anti-inflammatory properties that can protect the intestinal barrier.


Asunto(s)
Lipopolisacáridos , FN-kappa B , Humanos , FN-kappa B/metabolismo , Células CACO-2 , Lipopolisacáridos/farmacología , Cadenas Ligeras de Miosina , Lacticaseibacillus , Mucosa Intestinal/metabolismo , Calor , Quinasa de Cadena Ligera de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/farmacología , Fosforilación , Antiinflamatorios/farmacología , Uniones Estrechas/metabolismo
19.
J Clin Med ; 12(5)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36902511

RESUMEN

OBJECTIVES: Our study aimed to demonstrate the influence of left ventricular (LV) diastolic dysfunction on the diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR). METHODS: One hundred vessels from 90 patients were retrospectively analyzed. All patients underwent echocardiography, coronary computed tomography angiography (CCTA), CT-FFR, invasive coronary angiography (ICA), and fractional flow reserve (FFR). The study population was divided into normal and dysfunction groups according to the LV diastolic function, and the diagnostic performance in both groups was assessed. RESULTS: There was a good correlation between CT-FFR and FFR (R = 0.768 p < 0.001) on a per-vessel basis. The sensitivity, specificity, and accuracy were 82.3%, 81.8%, and 82%, respectively. The sensitivity, specificity, and accuracy were 84.6%, 88.5%, and 87.2% in the normal group and 81%, 77.5%, and 78.7% in the dysfunction group, respectively. CT-FFR showed no statistically significant difference in the AUC in the normal group vs. the dysfunction group (AUC: 0.920 [95% CI 0.787-0.983] vs. 0.871 [95% CI 0.761-0.943], Z = 0.772 p = 0.440). However, there was still a good correlation between CT-FFR and FFR in the normal group (R = 0.767, p < 0.001) and dysfunction group (R = 0.767 p < 0.001). CONCLUSIONS: LV diastolic dysfunction had no effect on the diagnostic accuracy of CT-FFR. CT-FFR has good diagnostic performance in both LV diastolic dysfunction and the normal group and can be used as an effective tool for finding lesion-specific ischemia while screening for arterial disease in patients.

20.
Dis Markers ; 2022: 6575052, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36393969

RESUMEN

Background: Renal transplantation can significantly improve the survival rate and quality of life of patients with end-stage renal disease, but the probability of acute rejection (AR) in adult renal transplant recipients is still approximately 12.2%. Machine learning (ML) is superior to traditional statistical methods in various clinical scenarios. However, the current AR model is constructed only through simple difference analysis or a single queue, which cannot guarantee the accuracy of prediction. Therefore, this study identified and validated new gene sets that contribute to the early prediction of AR and the prognosis prediction of patients after renal transplantation by constructing a more accurate AR gene signature through ML technology. Methods: Based on the Gene Expression Omnibus (GEO) database and multiple bioinformatic analyses, we identified differentially expressed genes (DEGs) and built a gene signature via LASSO regression and SVM analysis. Immune cell infiltration and immunocyte association analyses were also conducted. Furthermore, we investigated the relationship between AR genes and graft survival status. Results: Twenty-four DEGs were identified. A 5 gene signature (CPA6, EFNA1, HBM, THEM5, and ZNF683) were obtained by LASSO analysis and SVM analysis, which had a satisfied ability to differentiate AR and NAR in the training cohort, internal validation cohort and external validation cohort. Additionally, ZNF683 was associated with graft survival. Conclusion: A 5 gene signature, particularly ZNF683, provided insight into a precise therapeutic schedule and clinical applications for AR patients.


Asunto(s)
Trasplante de Riñón , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Calidad de Vida , Supervivencia de Injerto , Pronóstico , Riñón
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