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1.
Phys Chem Chem Phys ; 26(28): 19543-19553, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38979972

RESUMEN

Rational design of γ-alumina-based catalysts relies on an extensive understanding of the distribution of hydroxyl groups on the surface of γ-alumina and their physicochemical properties, which remain unclear and challenging to determine experimentally due to the structural complexity. In this work, by means of DFT and thermodynamic calculations, various hydroxylation modes of γ-alumina (110) and (100) surfaces at different OH coverages were evaluated, based on which a thermodynamic model to reflect the relationship between temperature and the surface structure was established and the stable hydroxylation modes under experimental conditions were predicted. This enables us to identify the experimentally measured IR spectra. The effect of hydroxyl coverages on the surface Lewis acidity was then analyzed, showing that the presence of hydroxyl groups could promote the Lewis acidity of neighboring Al sites. This work provides fundamental insights into the molecular level understanding of the surface properties of γ-alumina and benefits the rational design of alumina-based catalysts.

2.
BMJ Open ; 14(7): e082799, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025815

RESUMEN

BACKGROUND: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH. METHODS: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence. RESULTS: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability. CONCLUSIONS: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.


Asunto(s)
Anemia , Nomogramas , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Anemia/etiología , Anemia/diagnóstico , Anemia/sangre , Estudios Prospectivos , Anciano , Adulto , Aneurisma Intracraneal/complicaciones
3.
Nat Commun ; 15(1): 5747, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982069

RESUMEN

Friction as a fundamental physical phenomenon dominates nature and human civilization, among which the achievement of molecular rolling lubrication is desired to bring another breakthrough, like the macroscale design of wheel. Herein, an edge self-curling nanodeformation phenomenon of graphite nanosheets (GNSs) at cryogenic temperature is found, which is then used to promote the formation of graphite nanorollers in friction process towards molecular rolling lubrication. The observation of parallel nanorollers at the friction interface give the experimental evidence for the occurrence of molecular rolling lubrication, and the graphite exhibits abnormal lubrication performance in vacuum with ultra-low friction and wear at macroscale. The molecular rolling lubrication mechanism is elucidated from the electronic interaction perspective. Experiments and theoretical simulations indicate that the driving force of the self-curling is the uneven atomic shrinkage induced stress, and then the shear force promotes the intact nanoroller formation, while the constraint of atomic vibration decreases the dissipation of driving stress and favors the nanoroller formation therein. It will open up a new pathway for controlling friction at microscale and nanostructural manipulation.

4.
Chem Sci ; 15(27): 10491-10498, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38994426

RESUMEN

The development of novel near-infrared (NIR) materials with extremely small energy gaps and high stability is highly desirable in bioimaging and phototherapy. Here we report an effective strategy for narrowing the energy gaps of porphyrins by synergistic regulation of meso/ß substituents. The novel NIR absorbing/emitting meso-alkynyl naphthoporphyrins (Zn-TNP and Pt-TNP) are synthesized via the retro-Diels-Alder reaction. X-ray crystallography analysis confirms the highly distorted structures of the complexes. Both compounds exhibit intense Q bands around 800 nm, while Zn-TNP shows deep NIR fluorescence at 847 nm. Pt-TNP displays NIR-II room temperature phosphorescence peaking at 1106 nm with an extremely large Stokes shift of 314 nm, which are the longest wavelengths observed among the reported platinum porphyrinoids. Furthermore, Pt-TNP shows remarkable photostability and a notable capacity for synchronous singlet oxygen and heat generation under NIR light irradiation, demonstrating potential in combined photodynamic/photothermal therapy. A theoretical analysis reveals the progressive lifting of the HOMO by the ß-fused benzene ring, the decrease of the LUMO upon meso-alkynyl substitution, and energy-releasing pathways varying with metal ions. This dual regulation approach demonstrates great promise in designing innovative multifunctional NIR porphyrin materials.

5.
Cell Biol Int ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953242

RESUMEN

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. ACBD3 knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to ACBD3 knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, ACBD3 knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.

6.
J Colloid Interface Sci ; 675: 580-591, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38986331

RESUMEN

Single-atom nanozymes (SANZs) have emerged as new media for enhancing chemodynamic therapy (CDT) to achieve desirable enzyme-like effects and excellent nanoscale specificity. However, non-optimal adsorption of Fenton-like reaction intermediates prevents SANZs from exerting kinetic activity and hinders the CDT effect. Herein, we demonstrate that heteroatom-doped Co single-atom nanozymes (SACNZs) with intrinsic charge transfer exhibit peroxidase-like properties and significantly improve the ability of CDT to treat Staphylococcus aureus-infected wounds. Density functional theory calculations showed that the S-induced charge transfer effect regulated the electronic distribution of the central metal more efficiently than P, thereby lowering the energy levels for the generation of OH and increasing the catalytic effect. Polyvinylpyrrolidone-modified SACNZs showed effects consistent with this theory in both in vitro antibacterial and in vivo ward management assays. This study systematically investigated the relationship between heteroatom-doping and the catalytic activity of metal centres, opening a new perspective for the application of CDT.

7.
Scand J Immunol ; 99(4): e13352, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39008028

RESUMEN

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B-cell lymphoblastic leukaemia (R/R B-ALL). However, a subset of patients does not benefit from CAR-T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR-T therapy. Fifty-five R/R B-ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B-MRD) as indicators for predicting the success of CAR-T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3+ T count, CD4+ T/CD8+ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR-T therapy with AUC of 0.938. Notably, a model based on CD4+ T/CD8+ T ratio, B, Treg and EMD were used in predicting the success of CAR-T therapy with AUC 0.966 [0.908-1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR-T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR-T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR-T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR-T cell therapy.


Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Masculino , Femenino , Adulto , Adolescente , Persona de Mediana Edad , Receptores Quiméricos de Antígenos/inmunología , Niño , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Adulto Joven , Preescolar , Resultado del Tratamiento , Linfocitos T Reguladores/inmunología , Curva ROC , Recurrencia
8.
Langmuir ; 40(28): 14346-14354, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38953474

RESUMEN

The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS2) and iron sulfide (FeS2), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS2 significantly accelerates the conversion of Fe2+/Fe3+ through a cocatalytic reaction that involves the participation of redox pairs of Mo4+/Mo6+, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both in vitro and in vivo results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococcus aureus. The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.


Asunto(s)
Antibacterianos , Disulfuros , Hierro , Molibdeno , Sulfuros , Cicatrización de Heridas , Molibdeno/química , Molibdeno/farmacología , Cicatrización de Heridas/efectos de los fármacos , Sulfuros/química , Sulfuros/farmacología , Animales , Disulfuros/química , Disulfuros/farmacología , Hierro/química , Hierro/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Catálisis , Staphylococcus aureus/efectos de los fármacos , Ratones , Escherichia coli/efectos de los fármacos , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Nanoestructuras/química , Fototerapia , Pruebas de Sensibilidad Microbiana , Terapia Fototérmica , Compuestos Ferrosos
9.
J Adv Res ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960279

RESUMEN

INTRODUCTION: Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated. OBJECTIVES: This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma. METHODS: The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules. RESULTS: The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4. CONCLUSION: Our findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.

10.
Nanomaterials (Basel) ; 14(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38998712

RESUMEN

Magnetic metal absorbing materials have exhibited excellent absorptance performance. However, their applications are still limited in terms of light weight, low thickness and wide absorption bandwidth. To address this challenge, we design a broadband and low-profile multilayer absorber using cobalt-iron (CoFe) alloys doped with rare earth elements (REEs) lanthanum (La) and Neodymium (Nd). An improved estimation of distribution algorithm (IEDA) is employed in conjunction with a mathematical model of multilayer absorbing materials (MAMs) to optimize both the relative bandwidth with reflection loss (RL) below -10 dB and the thickness. Firstly, the absorption performance of CoFe alloys doped with La/Nd with different contents is analysed. Subsequently, IEDA is introduced based on a mathematical model to achieve an optimal MAM design that obtains a balance between absorption bandwidth and thickness. To validate the feasibility of our proposed method, a triple-layer MAM is designed and optimized to exhibit wide absorption bandwidth covering C, X, and Ku bands (6.16-12.82 GHz) and a total thickness of 2.39 mm. Then, the electromagnetic (EM) absorption mechanisms of the triple-layer MAMs are systematically investigated. Finally, the triple-layer sample is further fabricated and measured. The experimental result is in good agreement with the simulated result. This paper presents a rapid and efficient optimization method for designing MAMs, offering promising prospects in microwave applications, such as radar-stealth technology, EM shielding, and reduced EM pollution for electronic devices.

11.
Microbiome ; 12(1): 130, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026313

RESUMEN

BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.


Asunto(s)
Heces , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Viroma , Humanos , Microbioma Gastrointestinal/genética , Animales , Heces/virología , Heces/microbiología , Ratones , Enfermedades Inflamatorias del Intestino/virología , Enfermedades Inflamatorias del Intestino/microbiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Enfermedad de Crohn/virología , Enfermedad de Crohn/microbiología , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Colitis Ulcerosa/virología , Colitis Ulcerosa/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , China , Trasplante de Microbiota Fecal , Estudios de Casos y Controles , Virus/clasificación , Virus/aislamiento & purificación , Virus/genética
12.
Mater Horiz ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39026466

RESUMEN

The overuse of antibiotics has led to the rapid development of multi-drug resistant bacteria, making antibiotics increasingly ineffective against bacterial infections. Consequently, there is an urgent need to develop alternative strategies to combat multi-drug-resistant bacterial infections. In this study, gold nanoparticles modified with ellagic acid (EA-AuNPs) were prepared using a simple and mild one-pot hydrothermal process. EA-AuNPs demonstrated high bactericidal efficacy and broad-spectrum antimicrobial activities against clinical isolates of the antibiotic-resistant ESKAPE pathogens. Furthermore, EA-AuNPs effectively disperse biofilms of multi-drug-resistant bacteria. Additionally, EA-AuNPs mitigated inflammatory responses at the bacterial infection sites. The combined bactericidal and anti-inflammatory treatment with EA-AuNPs resulted in faster curing of peritonitis caused by Staphylococcus aureus in mice compared to treatment with free EA or gentamicin. Moreover, transcriptome analysis revealed that EA-AuNPs exhibited a multi-targeting mechanism, making resistance development in pathogens more challenging than traditional antibiotics that recognize specific cellular targets. Overall, EA-AuNPs emerged as a promising antimicrobial agent against multi-drug-resistant bacterial infections.

13.
Beilstein J Org Chem ; 20: 1405-1411, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952958

RESUMEN

Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity.

14.
Small ; : e2403903, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953301

RESUMEN

Asymmetric electronic environments based on microscopic-scale perspective have injected infinite vitality in understanding the intrinsic mechanism of polarization loss for electromagnetic (EM) wave absorption, but still exists a significant challenge. Herein, Zn single-atoms (SAs), structural defects, and Co nanoclusters are simultaneously implanted into bimetallic metal-organic framework derivatives via the two-step dual coordination-pyrolysis process. Theoretical simulations and experimental results reveal that the electronic coupling interactions between Zn SAs and structural defects delocalize the symmetric electronic environments and generate additional dipole polarization without sacrificing conduction loss owing to the compensation of carbon nanotubes. Moreover, Co nanoclusters with large nanocurvatures induce a strong interfacial electric field, activate the superiority of heterointerfaces and promote interfacial polarization. Benefiting from the aforementioned merits, the resultant derivatives deliver an optimal reflection loss of -58.9 dB and the effective absorption bandwidth is 5.2 GHz. These findings provide an innovative insight into clarifying the microscopic loss mechanism from the asymmetric electron environments viewpoint and inspire the generalized electronic modulation engineering in optimizing EM wave absorption.

15.
Front Vet Sci ; 11: 1390473, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835897

RESUMEN

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

16.
Cell Metab ; 36(6): 1269-1286.e9, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38838640

RESUMEN

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD.


Asunto(s)
Progresión de la Enfermedad , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Humanos , Ratones , Masculino , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Monocitos/metabolismo , Femenino , Persona de Mediana Edad , Inflamación/patología , Inflamación/metabolismo , Hepatocitos/metabolismo , Hepatocitos/patología , Hígado/patología , Hígado/metabolismo , Moléculas de Adhesión Celular/metabolismo
17.
Sci Rep ; 14(1): 13691, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871835

RESUMEN

Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Benzoxazoles , United States Food and Drug Administration , Estados Unidos , Humanos , Benzoxazoles/efectos adversos , Neuropatías Amiloides Familiares , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Vigilancia de Productos Comercializados , Masculino
18.
Biomed Pharmacother ; 177: 116971, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38901201

RESUMEN

Thyroid cancer is a prevalent endocrine malignancy whose global incidence has risen over the past several decades. Ferroptosis, a regulated form of cell death distinguished by the excessive buildup of iron-dependent lipid peroxidates, stands out from other programmed cell death pathways in terms of morphological and molecular characteristics. Increasing evidence suggests a close association between thyroid cancer and ferroptosis, that is, inducing ferroptosis effectively suppresses the proliferation of thyroid cancer cells and impede tumor advancement. Therefore, ferroptosis represents a promising therapeutic target for the clinical management of thyroid cancer in clinical settings. Alterations in ferroptosis-related genes hold potential for prognostic prediction in thyroid cancer. This review summarizes current studies on the role of ferroptosis in thyroid cancer, elucidating its mechanisms, therapeutic targets, and predictive biomarkers. The findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of innovative treatment strategies and accurate predictors for the thyroid cancer.

19.
Saudi Pharm J ; 32(7): 102123, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38911279

RESUMEN

Biodegradable and biocompatible biomaterials have several important applications in drug delivery. The biomaterial family known as poly(ester amide)s (PEAs) has garnered considerable interest because it exhibits the benefits of both polyester and polyamide, as well as production from readily available raw ingredients and sophisticated synthesis techniques. Specifically, α-amino acid-based PEAs (AA-PEAs) are promising carriers because of their structural flexibility, biocompatibility, and biodegradability. Herein, we summarize the latest applications of PEAs in drug delivery systems, including antitumor, gene therapy, and protein drugs, and discuss the prospects of drug delivery based on PEAs, which provides a reference for designing safe and efficient drug delivery carriers.

20.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868877

RESUMEN

BACKGROUND: This study aimed to improve the accuracy of the fibrinogen (Fib) prothrombin time-derived (PT-der) method. To achieve this, a value transfer method was introduced for calibration, and its effectiveness was assessed. METHODS: The PT-der Fib assay was calibrated by pooled samples (assigned by the von Clauss method) in three different ways: 1) multipoint calibration using an automatic dilution system, 2) multipoint calibration using a manual dilution method, and 3) manual calibration with multiple concentrations. Three calibration equations (1, 2, and 3) were obtained and an optimal equation was selected by comparing the detection results of the von Clauss method with the PT-der method. Subsequently, the optimal equation was assessed for an accuracy limit, and linear analysis and reference interval verification were performed following the guidelines (EP15-A and EP6-A) issued by the CLSI. RESULTS: Compared with the other two equations (equation 1 and 2), equation 3, available from manual calibration with multiple concentrations, showed a better performance for the PT-der determination in a primary cohort (n = 208), and a good agreement (99% of the results between 1.52 and 6.30 g/L were interchangeable) was validated (n = 3226). The reference interval was also verified in almost all healthy individuals (39/40). However, the discrep-ancy between the two methods was observed in several specific conditions, such as hyperfibrinolysis. CONCLUSIONS: Manual calibration with multiple concentrations is better for the Fib PT-der method assay. As a rapid, accurate, and economical test, the performance of the Fib PT-der method has been verified and may be more applicable than before.


Asunto(s)
Fibrinógeno , Tiempo de Protrombina , Humanos , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Tiempo de Protrombina/métodos , Calibración , Adulto , Valores de Referencia , Femenino , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven , Anciano , Adolescente , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Anciano de 80 o más Años
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