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1.
J Environ Sci (China) ; 148: 57-68, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095190

RESUMEN

The expandable graphite (EG) modified TiO2 nanocomposites were prepared by the high shear method using the TiO2 nanoparticles (NPs) and EG as precursors, in which the amount of EG doped in TiO2 was 10 wt.%. Followed by the impregnation method, adjusting the pH of the solution to 10, and using the electrostatic adsorption to achieve spatial confinement, the Pt elements were mainly distributed on the exposed TiO2, thus generating the Pt/10EG-TiO2-10 catalyst. The best CO oxidation activity with the excellent resistance to H2O and SO2 was obtained over the Pt/10EG-TiO2-10 catalyst: CO conversion after 36 hr of the reaction was ca. 85% under the harsh condition of 10 vol.% H2O and 100 ppm SO2 at a high gaseous hourly space velocity (GHSV) of 400,000 hr-1. Physicochemical properties of the catalysts were characterized by various techniques. The results showed that the electrostatic adsorption, which riveted the Pt elements mainly on the exposed TiO2 of the support surface, reduced the dispersion of Pt NPs on EG and achieved the effective dispersion of Pt NPs, hence significantly improving CO oxidation activity over the Pt/10EG-TiO2-10 catalyst. The 10 wt.% EG doped in TiO2 caused the TiO2 support to form a more hydrophobic surface, which reduced the adsorption of H2O and SO2 on the catalyst, greatly inhibited deposition of the TiOSO4 and formation of the PtSO4 species as well as suppressed the oxidation of SO2, thus resulting in an improvement in the resistance to H2O and SO2 of the Pt/10EG-TiO2-10 catalyst.


Asunto(s)
Grafito , Oxidación-Reducción , Platino (Metal) , Dióxido de Azufre , Titanio , Titanio/química , Grafito/química , Dióxido de Azufre/química , Platino (Metal)/química , Catálisis , Monóxido de Carbono/química , Agua/química , Contaminantes Atmosféricos/química , Modelos Químicos
2.
Clin Ther ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39242322

RESUMEN

PURPOSE: Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. METHODS: Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. FINDINGS: GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. IMPLICATIONS: This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.

3.
Front Endocrinol (Lausanne) ; 15: 1428125, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234503

RESUMEN

Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1. Results: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG. Conclusion: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.


Asunto(s)
Necrosis de la Cabeza Femoral , Osteonecrosis , Humanos , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Necrosis de la Cabeza Femoral/terapia , Metaanálisis en Red , Osteonecrosis/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
4.
Artículo en Inglés | MEDLINE | ID: mdl-39222472

RESUMEN

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. METHODS: Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1ß, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. RESULTS: High levels of TRAIL, CXCL12, and IL-1ß were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1ß: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1ß, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). CONCLUSION: Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.

5.
Sci Rep ; 14(1): 21639, 2024 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284844

RESUMEN

Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.


Asunto(s)
Capsicum , Manipulación de Alimentos , Capsicum/química , Manipulación de Alimentos/métodos , Ácidos Grasos/análisis , Fenoles/análisis , Desecación/métodos , Gusto , Valor Nutritivo , Capsaicina/análisis
6.
Front Cardiovasc Med ; 11: 1445076, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267809

RESUMEN

Introduction: The morbidity and mortality rates of coronary heart disease are significant, with PCI being the primary treatment. The high incidence of ISR following PCI poses a challenge to its effectiveness. Currently, there are numerous studies on ISR risk prediction models after PCI, but the quality varies and there is still a lack of systematic evaluation and analysis. Methods: To systematically retrieve and evaluate the risk prediction models for ISR after PCI. A comprehensive search was conducted across 9 databases from inception to March 1, 2024. The screening of literature and extraction of data were independently carried out by two investigators, utilizing the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS). Additionally, the risk of bias and applicability were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Results: A total of 17 studies with 29 models were included, with a sample size of 175-10,004 cases, and the incidence of outcome events was 5.79%-58.86%. The area under the receiver operating characteristic curve was 0.530-0.953. The top 5 predictors with high frequency were diabetes, number of diseased vessels, age, LDL-C and stent diameter. Bias risk assessment into the research of the risk of higher bias the applicability of the four study better. Discussion: The overall risk of bias in the current ISR risk prediction model post-PCI is deemed high. Moving forward, it is imperative to enhance study design and specify the reporting process, optimize and validate the model, and enhance its performance.

7.
Chempluschem ; : e202400302, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230969

RESUMEN

The organic-inorganic hybrid fluorescent hyperbranched polymer, including hyperbranched polysiloxane and hyperbranched polyborate, have attracted much attention due to their excellent optical properties and wide range of applications. Hyperbranched polysiloxane and polyborates, prepared by introducing Si or B elements into organic polymer chains at the molecular level through rational molecular design and novel synthesis methods, exhibit outstanding photophysical properties as an indispensable branch of organic-inorganic hybrid fluorescent materials. Herein, this review article highlights the recent research progress on hyperbranched polysiloxanes and hyperbranched polyborates, including strategies for regulating their emission wavelengths, quantum yields, and fluorescence lifetimes, potential emission mechanisms, and various applications. Finally, some challenges and promising future directions in the field of organic-inorganic hybrid fluorescent polymers are summarized.

8.
Arch Gerontol Geriatr ; 128: 105626, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39270436

RESUMEN

OBJECTIVE: To investigate the interplay between individual nighttime and midday sleep duration and the number of new-onset chronic diseases and determine the optimal sleep duration associated with lowest number of new-onset chronic diseases. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS) covering a decade and involving 10,828 participants. A random intercept cross-lagged model was used to explore the interplay between nighttime/midday sleep durations and new-onset chronic diseases at both the within-individual and between-individual levels, followed by a dose-response analysis at the between-individual level to determine the optimal sleep duration. New-onset chronic diseases include 14 types of self-reported diseases diagnosed by doctors. RESULTS: Within-individual analysis revealed that increased nighttime/midday sleep duration led to a higher number of new-onset chronic diseases, and an increased number of new-onset chronic diseases resulted in decreased nighttime sleep duration. Between nighttime and midday sleep, one type of sleep duration increase was likely to lead to an increase in another type. Between-individual analysis found a nonlinear relationship between the number of new-onset chronic diseases and nighttime sleep duration, identifying the optimal nighttime sleep duration as 7.46 h. CONCLUSIONS: These findings elucidate the interplay between sleep duration and number of new-onset chronic diseases and underscore the need for public awareness and comprehensive interventions. Future studies should focus on refining sleep monitoring and exploring the sleep-chronic diseases nexus in greater depth.

9.
Front Microbiol ; 15: 1459124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257615

RESUMEN

Pasteurella multocida toxin (PMT) is one of the most important virulence factors of Pasteurella multocida type D. Pasteurella multocida infection has caused enormous economic losses in the pig farming industry. Although it is well known that this bacterial infection causes progressive atrophic rhinitis, its effects on other organ tissues in pigs are unclear. In this study, PMT was expressed and purified, and the cytotoxic effects of PMT on four types of swine cells, LLC-PK1, PAM, IPEC, and ST, were investigated. LLC-PK1 exhibited the highest sensitivity to the cytotoxic effects of PMT. Our studies revealed that a PMT concentration of 0.1 µg/kg can lead to weight loss, whereas a PMT concentration of 0.5 µg/kg can lead to death in mice. PMT causes damage to the intestines, kidneys, lungs, livers, and spleens of mice. Furthermore, PMT caused acute death in pigs at treatment concentrations greater than 5 µg/kg; at PMT concentration of 2.5 µg/kg, weight loss occurred until death. PMT mainly caused damage to the hearts, lungs, livers, spleens and kidneys of pigs. The organ coefficient showed that damage to the heart and kidneys was the most severe and caused the renal pelvis and renal pyramid to dissolve and become cavitated. Pathology revealed hemorrhage in the lungs, liver, and spleen, and the kidneys were swollen and vacuolated, which was consistent with the damaged target organs in the mice. In conclusion, these findings demonstrate that PMT is extremely toxic in vitro and in vivo, causing damage to various organs of the body, especially the kidneys and lungs. This study provides a theoretical basis for the in-depth exploration of the cytotoxic effects of PMT on target organs.

10.
Eur J Med Chem ; 279: 116851, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39255644

RESUMEN

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a promising target for the diagnosis and treatment of various diseases, especially neurodegenerative disorders. Developing PET imaging probes targeting RIPK1 is beneficial for visualizing the connections between RIPK1 and diseases, as well as for related drug development. In this study, we report the design and synthesis of a series of novel RIPK1 inhibitors. Three potent inhibitors, 7i, 7k, and 8a, with good cell anti-necroptosis potency and physicochemical properties, were identified and selected for PET imaging probe development. Subsequently, three PET imaging radioligands ([11C]7k, [18F]7i, and [18F]8a) were successfully synthesized. In mouse PET imaging studies, all three radioligands showed good brain uptake. Among them, probe [18F]8a exhibited good binding specificity in both in vitro autoradiography and in vivo PET imaging studies. Additionally, [18F]8a demonstrated good in vivo metabolic stability. This work highlights the potential of probe [18F]8a for imaging brain RIPK1 in live animals, laying the groundwork for the future development of RIPK1 PET radioligands.

11.
Front Pharmacol ; 15: 1386794, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206264

RESUMEN

Introduction: Obesity, a global epidemic, is caused by an imbalance between energy intake and expenditure. The induction of white adipose browning to increase heat production has emerged as a potential effective strategy to address obesity. Ling-gui-zhu-gan (LGZG), a traditional Chinese medicine formula, has been proved to achieve promising results to combat obesity and related metabolic diseases, yet the mechanisms remain largely unexplored. This study aimed to elucidate the anti-obesity properties and the mechanisms of LGZG by investigating its browning effect on 3T3-L1 adipocytes. Methods: LGZG-containing serum obtained by oral administration of LGZG to animals was added to 3T3-L1 adipocytes to simulate in vivo conditions. Results: The results showed that 49 compounds were identified in LGZG-containing serum by UHPLC-Q-Orbitrap HRMS, including compounds such as atractylenolides and polyporenic acid C, etc. LGZG-containing serum alleviated the lipid accumulation and decreased both intracellular and extracellular triglyceride contents in a dose-dependent manner. This reduction is accompanied by enhanced mitochondrial respiratory and heat production function. Mechanistically, LGZG-containing serum led to a decrease in miR-27b expression and an increase in the mRNA and protein levels of browning-related markers, including UCP1, PRDM16, PGC-1α, PPARγ, CTBP1, and CTBP2. Further investigation using miR-27b mimic transfection confirmed that miR-27b/PRDM16 pathway might be a potential mechanism by which LGZG-containing serum promotes browning of 3T3-L1 adipocytes. Discussion: These results underscore the therapeutic potential of LGZG in addressing obesity and its associated metabolic disorders through the promotion of adipose browning.

12.
Bioanalysis ; : 1-14, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115055

RESUMEN

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection. Methods: Around 10 mmNH4Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis. Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.


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13.
Int J Biol Macromol ; 278(Pt 1): 134662, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128732

RESUMEN

Lead is a common environmental pollutant which can accumulate in the kidney and cause renal injury. However, regulatory effects and mechanisms of Sparassis latifolia polysaccharide (SLP) on lipid metabolism abnormality in kidney exposed to lead are not clarified. In this study, mice were used to construct an animal model to observe the histopathological changes in kidney, measure lead content, damage indicators, differentially expressed metabolites (DEMs) and genes (DEGs) in key signaling pathways that cause lipid metabolism abnormalities based on lipidomics and transcriptomics, which were later validated using qPCR and western blotting. Co-treatment of Pb and N-acetylcysteine (NAC) were used to verify the link between SLP and oxidative stress. Our results indicated that treatment with SLP identified 276 DEMs (including metabolism of glycerophospholipid, sphingolipid, glycerolipid and fatty acid) and 177 DEGs (including genes related to oxidative stress, inflammation, autophagy and lipid metabolism). Notably, regulatory effects of SLP on abnormal lipid metabolism in kidney were mainly associated with oxidative stress, inflammation and autophagy; SLP could regulate abnormal lipid metabolism in kidney by reducing oxidative stress and affecting its downstream-regulated autophagy and inflammatory to alleviate renal injury caused by lead exposure. This study provides a theoretical basis for SLP intervention in lead injury.


Asunto(s)
Autofagia , Inflamación , Riñón , Plomo , Metabolismo de los Lípidos , Estrés Oxidativo , Polisacáridos , Animales , Estrés Oxidativo/efectos de los fármacos , Ratones , Autofagia/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Polisacáridos/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Plomo/toxicidad , Masculino , Lipidómica , Multiómica
14.
Eur J Appl Physiol ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212731

RESUMEN

PURPOSE: to investigate the early consequences of type 1 diabetes (T1D) on the neural strategies of muscle force production. METHODS: motor unit (MU) activity was recorded from the vastus lateralis muscle with High-Density surface Electromyography during isometric knee extension at 20 and 40% of maximum voluntary contraction (MVC) in 8 T1D (4 males, 4 females, 30.5 ± 3.6 years) and 8 matched control (4 males, 4 females, 27.3 ± 5.9 years) participants. Muscle biopsies were also collected from vastus lateralis for fiber type analysis, including myosin heavy chain (MyHC) isoform content via protein and mRNA expression. RESULTS: MVC was comparable between groups as well as MU conduction velocity, action potentials' amplitude and proportions of MyHC protein isoforms. Nonetheless, MU discharge rate, relative derecruitment thresholds and mRNA expression of MyHC isoform I were lower in T1D. CONCLUSIONS: young people with uncomplicated T1D present a different neural control of muscle force production. Furthermore, differences are detectable non-invasively in absence of any functional manifestation (i.e., force production and fiber type distribution). These novel findings suggest that T1D has early consequences on the neuromuscular system and highlights the necessity of a better characterization of neural control in this population.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39215904

RESUMEN

Imaging probe and contrast agents play significant role in combating cancer. Based on special chemical materials, imaging probe can convert cancer symptoms into information-rich images with high sensitivity and signal amplification, accompanying with detection, diagnosis, drug delivery and treatment. In the paper, some inorganic and organic chemical materials as imaging probe, including Ultrasound imaging (US), Optical imaging (OP), Photoacoustic imaging (PA), X-ray Computed Tomography (CT), Magnetic Resonance imaging (MRI), Radionuclide imaging (RNI) probe, as well as multi-modality imaging probe for diagnosis and therapy of tumour were introduced. The sophisticated and comprehensive chemical materials as imaging probe were highlighted in detail. Meanwhile, the advantages and disadvantages of the imaging probe were compared. In order to provide some reference and help researchers for construction imaging probe for tumour diagnosis and treatment, it attempts to exhaustively cover the whole field. Finally, the prospect and challenge for imaging probe were discussed.

16.
J Nanobiotechnology ; 22(1): 518, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210464

RESUMEN

Deoxyribonucleotide (DNA) is uniquely programmable and biocompatible, and exhibits unique appeal as a biomaterial as it can be precisely designed and programmed to construct arbitrary shapes. DNA hydrogels are polymer networks comprising cross-linked DNA strands. As DNA hydrogels present programmability, biocompatibility, and stimulus responsiveness, they are extensively explored in the field of biomedicine. In this study, we provide an overview of recent advancements in DNA hydrogel technology. We outline the different design philosophies and methods of DNA hydrogel preparation, discuss its special physicochemical characteristics, and highlight the various uses of DNA hydrogels in biomedical domains, such as drug delivery, biosensing, tissue engineering, and cell culture. Finally, we discuss the current difficulties facing DNA hydrogels and their potential future development.


Asunto(s)
Materiales Biocompatibles , ADN , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , ADN/química , Humanos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Ingeniería Biomédica/métodos , Técnicas Biosensibles/métodos , Técnicas de Cultivo de Célula/métodos
17.
Oncogene ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164523

RESUMEN

The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy. We unrevealed a notable association between the inclusion of exon 7.2 in the 5'untranslated region (5'UTR) of ALDOA mRNA and TAM resistance. Mechanistically, the inclusion of ALDOA exon 7.2 enhances the translation efficiency of the transcript, resulting in increased ALDOA protein expression, mTOR pathway activity, and the promotion of TAM resistance in breast cancer cells. Moreover, the inclusion of exon 7.2 in ALDOA mRNA is mediated by MSI1 via direct interaction. In addition, elevated inclusion of ALDOA exon 7.2 or expression of MSI1 is associated with an unfavorable prognosis in patients undergoing endocrine therapy. Notably, treatment with Aldometanib, an ALDOA inhibitor, effectively restrains the growth of TAM-resistant breast cancer cells in vitro and in vivo. The present study unveils the pivotal role of an AS event in ALDOA, under the regulation of MSI1, in driving TAM resistance in breast cancer. Therefore, this study provides a promising therapeutic avenue targeting ALDOA to combat TAM resistance.

18.
Front Physiol ; 15: 1427722, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156823

RESUMEN

Background: Ling-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity. Methods: Male C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting. Results: The results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues. Conclusion: Our findings position LGZG as a novel strategy for preventing obesity and improving metabolic health.

19.
Artículo en Inglés | MEDLINE | ID: mdl-39108009

RESUMEN

BACKGROUND: Zinc finger C3H1-type containing (ZFC3H1) might regulate RNA processes. However, research lacks the prognostic value of ZFC3H1 in hepatocellular carcinoma (HCC). METHODS: The study analyzed ZFC3H1 expression in HCC cells and its correlation with patient prognosis using transcriptomics, immunohistochemistry, and quantitative real-time reverse transcription PCR, as well as single-cell RNA expression data. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to investigate the potential ZFC3H1-related cellular functions and signaling pathways. The impact of ZFC3H1 expression on the tumor microenvironment and tumor mutational burden (TMB) was assessed using the ESTIMATE algorithm. Cell-based assays, including cell counting kit 8, proliferation, colony formation, cell cycle, wound healing, and Transwell assays, were conducted to evaluate the influence of ZFC3H1 on hepatocellular carcinoma proliferation and migration. RESULTS: ZFC3H1 is upregulated in HCC and linked to tumor progression. High ZFC3H1 expression is a prognostic risk factor for HCC, according to Kaplan-Meier and Cox regression analyses. ESTIMATE analysis suggested that ZFC3H1 reduces immune cell infiltration and increases the TMB. Patients with low ZFC3H1 expression might respond better to immunotherapy. High ZFC3H1 expression is associated with increased half-maximal inhibitory concentration (IC50) of sorafenib. Functional experiments demonstrated that reducing ZFC3H1 expression inhibited HCC cell proliferation and migration. CONCLUSION: ZFC3H1 is upregulated in HCC, promoting the proliferation and migration of liver cancer cells, impacting the prognosis of HCC patients and the effectiveness of immunotherapy. ZFC3H1 might serve as a therapeutic target and biomarker for HCC.

20.
Heart Lung ; 68: 272-278, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39142089

RESUMEN

BACKGROUND: Early identification of risk factors for adverse COVID-19 progression in patients with autoimmune diseases is crucial for patient management, but data on the Chinese population are scarce. OBJECTIVES: The purpose of this study was to identify predictors of severe COVID-19 in patients using blood cell ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and other inflammatory markers. METHODS: A retrospective study of 855 patients (746 females; median age 49 years) with autoimmune diseases and concurrent COVID-19 was conducted from December 2022 to February 2023 at the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University. Disease severity was assessed according to the 8th edition of the National Health Commission of the People's Republic of China's COVID-19 Diagnosis and Treatment Guidelines. The clinical classification criteria group mild and moderate cases as nonsevere cases and severe and critical cases as severe cases. A multivariate logistic regression model was established to evaluate the relationships between COVID-19 severity and demographic characteristics, comorbidities, medication use, and laboratory findings. RESULTS: The PLR, NLR, and SII were significantly greater in the severe COVID-19 group than in the nonsevere group (all P < 0.05). In addition to classical independent clinical risk factors, increases in the PLR (OR: 1.004, 95 % CI: 1.001∼1.007, p = 0.001), NLR (OR: 1.180, 95 % CI: 1.041∼1.337, p = 0.010), and SII (OR: 0.999, 95 % CI: 0.998∼1.000, p = 0.005) were identified as risk factors for severe COVID-19 in patients with autoimmune diseases. After adjusting for clinical risk factors, the PLR (AUC: 0.592 vs. 0.865; P < 0.05), NLR (AUC: 0.670 vs. 0.866; P < 0.05), and SII (AUC: 0.616 vs. 0.864; P < 0.05) demonstrated higher predictive values. CONCLUSION: Early prediction of severe COVID-19 in patients with autoimmune diseases can be achieved using the NLR, PLR, and SII.

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