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1.
Artículo en Inglés | MEDLINE | ID: mdl-39369853

RESUMEN

BACKGROUND: Leukotriene-receptor antagonists (LTRA) and inhaled corticosteroids (ICS) are common controller medications for asthma, but limited studies examine their comparative risks on neuropsychiatric adverse events (NAEs) in asthma patients. OBJECTIVE: To investigate the comparative risks of LTRA versus ICS on seven distinct categories of NAEs in asthma patients at a nationwide level. METHODS: We conducted a nationwide cohort study during 2010-2021. Incident NAEs and its clinical subgroups (e.g., psychotic disorders, anxiety disorders, movement disorders, behavioral and emotional disorders, mood disorders, sleep-related disorders, and personality disorders) were assessed. Cox proportional hazards regressions were employed to quantify the comparative risks. RESULTS: There were 1,249,897 asthma patients aged 6-64 years. Incidence rates for NAEs were 25.10 per 1000 person-years among patients treated with LTRA, and 23.46 per 1000 person-years among those treated with ICS. The incidence rate difference was 1.64 [95%CI: 0.30-2.98] per 1000 person-years. Positive associations of NAEs and three clinical subgroups were found in patients treated with LTRA compared to ICS (hazard ratios (HR): 1.06 [95%CI: 1.00-1.12] for NAEs; HR: 1.88 [95%CI: 1.24-2.84] for psychotic disorders; HR: 1.10 [95%CI: 1.01-1.20] for anxiety disorders; and HR: 1.27 [95%CI: 1.02-1.58] for behavioral and emotional disorders), but not for movement disorders, mood disorders, sleep-related disorders, and personality disorders. CONCLUSIONS: This nationwide cohort study identified heightened risks, ranging from 6% to 88%, of NAEs and three clinical subgroups in asthma patients treated with LTRA compared to ICS. These findings underscore the necessity for clinicians to communicate with patients regarding potential neuropsychiatric harms when prescribing LTRA.

2.
Clin Otolaryngol ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358666

RESUMEN

OBJECTIVE: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22). DESIGN: A prospective cross-sectional study. SETTING: The rhinology ward at our institution, a tertiary hospital. PARTICIPANTS: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22. RESULTS: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists. CONCLUSION: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30.

3.
J Asthma ; : 1-10, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269783

RESUMEN

OBJECTIVE: This study aimed to explore the effects of Parkin (Prkn) knockout in a juvenile mouse model of asthma. METHODS: Prkn knockout (KO) and wild type (WT) mice were utilized to establish a juvenile mouse asthma model. The asthma model involved exposure to hyperoxia/ovalbumin (OVA), encompassing hyperoxia from postnatal day 1 (P1) to P7, sensitization on P21 and P28, and challenge from P36 to P42. Room air/phosphate-buffered saline (PBS) served as the control condition. Following airway resistance measurement, bronchoalveolar lavage fluid (BALF) was collected for cellular analysis, and lung tissues were subjected to histological examination and oxidative stress assessment. Serum levels of ovalbumin-specific immunoglobulin E (IgE), total IgE, interleukin-4 (IL-4), IL-5, and IL-13 were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: WT mice exposed to hyperoxia/OVA showed decreased body weight and increased airway resistance compared to those exposed to control condition. Conversely, KO mice exhibited increased body weight under asthma conditions. KO mice with asthma had reduced total cell counts, along with lower levels of lymphocytes, eosinophils, and neutrophils, compared to WT asthma mice. Histological assessment showed attenuated inflammation and reduced collagen deposition in KO mice relative to WT mice, with lower serum levels of inflammatory markers and improved lung oxidative stress profiles. No significant differences were observed between KO and WT mice under room air/PBS conditions. CONCLUSIONS: Parkin knockout in juvenile mice mitigates asthma-related alterations in airway resistance, histopathological changes, inflammation status, and oxidative stress. These findings highlight a protective role of Parkin deficiency against asthma-associated pathologies.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39320506

RESUMEN

Nanoassemblies based on drug conjugates with high drug loading efficiency and stability have been regarded as promising candidates for the next generation of drug formulations. However, they are mostly amphiphilic. Here, a dual-hydrophobic drug conjugate-based nanoassembly has been created for enhanced synergistic antiproliferation against colorectal cancer cells. Camptothecin (CPT) and doxorubicin (DOX) were chosen as the hydrophobic drugs and covalently linked with a disulfide bond (-ss-). The synthesized CPT-ss-DOX can self-assemble into nanocubes (NCs) in an aqueous solution with the assistance of a small amount of polyethylene glycol (PEG), named PEGylated CPT-ss-DOX NCs. The PEGylated CPT-ss-DOX NCs were approximately 111.8 nm, possessing a crystal structure and a very low critical aggregation concentration (8.36 µg·mL-1). The self-assembly mechanism was studied using molecular docking and molecular dynamic simulation methods. The NCs demonstrated excellent storage stability and improved water solubility of CPT and DOX. These NCs could be taken up by cancer cells and gradually release the drugs. In addition, they had higher toxicity to cancer cells than a mixture of CPT and DOX, while they displayed reduced toxicity to normal cells. Due to assembly and PEG modification, the NCs improved drug retention time and enhanced accumulation at the tumor site. More importantly, they significantly inhibited colorectal tumor growth (58.37%) in vivo, superior to the CPT+DOX mix (42.63%). Moreover, the NCs reduced the cardiac toxicity of free drugs. Therefore, the prepared PEGylated CPT-ss-DOX NCs hold great potential for clinical transformation and provide a novel method for the self-delivery of hydrophobic molecules in cancer therapy.

5.
Chem Commun (Camb) ; 60(77): 10692-10695, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39239662

RESUMEN

A mechanism based on multiple hydrogen bonds was proposed to describe the great water stability of some hydrated Cu paddle-wheel-based MOFs, which was demonstrated through density functional theory (DFT) calculations and single-crystal X-ray diffraction (SCXRD) of water-loaded MOFs. This mechanism endowed Cu-TDPAT with exceptional water stability and outstanding atmospheric water harvesting capability.

6.
Pharmaceuticals (Basel) ; 17(9)2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39338366

RESUMEN

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with myocardial fatty acid metabolism. Carnitine palmitoyltransferase-1ß (CPT-1ß) is the rate-limiting enzyme responsible for ß-oxidation of long-chain fatty acids. Intermedin (IMD) is a pivotal bioactive small molecule peptide, participating in the protection of various cardiovascular diseases. However, the role and underlying mechanisms of IMD in DCM are still unclear. In this study, we investigated whether IMD alleviates DCM via regulating CPT-1ß. A rat DCM model was established by having rats to drink fructose water for 12 weeks. A mouse DCM model was induced by feeding mice a high-fat diet for 16 weeks. We showed that IMD and its receptor complexes levels were significantly down-regulated in the cardiac tissues of DCM rats and mice. Reduced expression of IMD was also observed in neonatal rat cardiomyocytes treated with palmitic acid (PA, 300 µM) in vitro. Exogenous and endogenous IMD mitigated cardiac hypertrophy, fibrosis, dysfunction, and lipid accumulation in DCM rats and IMD-transgenic DCM mice, whereas knockout of IMD worsened these pathological processes in IMD-knockout DCM mice. In vitro, IMD alleviated PA-induced cardiomyocyte hypertrophy and cardiac fibroblast activation. We found that CPT-1ß enzyme activity, mRNA and protein levels, and acetyl-CoA content were increased in T2DM patients, rats and mice. IMD up-regulated the CPT-1ß levels and acetyl-CoA content in T2DM rats and mice. Knockdown of CPT-1ß blocked the effects of IMD on increasing acetyl-CoA content and on inhibiting cardiomyocyte hypertrophy and cardiac fibroblast activation. IMD receptor antagonist IMD17-47 and the phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt) inhibitor LY294002 reversed the effects of IMD on up-regulating CPT-1ß and acetyl-CoA expression and on inhibiting cardiomyocyte hypertrophy and cardiac fibroblast activation. We revealed that IMD alleviates DCM by up-regulating CPT-1ß via calcitonin receptor-like receptor/receptor activity-modifying protein (CRLR/RAMP) receptor complexes and PI3K/Akt signaling. IMD may serve as a potent therapeutic target for the treatment of DCM.

7.
J Agric Food Chem ; 72(38): 20892-20904, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39255954

RESUMEN

Apple ring rot, caused by the pathogenic fungus Botryosphaeria dothidea, has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against B. dothidea, with an EC50 value of 8.8 µg/mL. Transcriptome, metabolome, and physiological assays revealed that DTB may target mitochondria and disrupt the tricarboxylic acid (TCA) cycle and oxidative phosphorylation processes. This interference led to increased accumulation of reactive oxygen species and subsequent lipid peroxidation, ultimately inhibiting fungal growth. Furthermore, DTB exhibited an inhibitory potency against apple ring rot at a concentration of 31.2 µg/mL, achieving rates ranging from 67.7 to 81.6% across four distinct apple cultivars. These results indicated that DTB could serve as a novel fungicide for controlling apple ring rot in apple cultivation, transportation, and storage.


Asunto(s)
Ascomicetos , Fungicidas Industriales , Malus , Enfermedades de las Plantas , Malus/microbiología , Malus/química , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Ascomicetos/efectos de los fármacos , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Diterpenos/farmacología , Diterpenos/química , Frutas/microbiología , Frutas/química
8.
Eur J Pharmacol ; 983: 176998, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39271038

RESUMEN

BACKGROUND: Bacterial keratitis is a common cause of blindness. Antibiotic treatment leads to the rapid release of lipopolysaccharide (LPS), which can activate corneal fibroblasts and cause persistent and excessive inflammatory responses. The anti-inflammatory drugs currently used to treat keratitis have serious side effects. Therefore, the ability of sodium butyrate (NaB), which can suppress the production of proinflammatory cytokines and promote the production of anti-inflammatory cytokines, to ameliorate keratitis was assessed in the present study. METHODS: The effect of NaB on the viability of primary human corneal fibroblasts was assayed with a CCK-8 kit. Cell migration was assessed by an in vitro scratch assay. Cell phenotypes were assessed by Western blotting and immunofluorescence staining. An antibody array was used to measure the production of proinflammatory cytokines and chemokines. RESULTS: At 0-1 mM, NaB had no significant effect on cell viability, promoted the expression of the keratocyte marker keratocan and inhibited the fibroblast marker vimentin. Inhibition of cell migration was observed in the wound healing assay. By targeting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, NaB decreased the levels of inflammation-related cytokines and chemokines whose expression was induced by LPS. CONCLUSIONS: NaB maintained the keratocyte phenotype, inhibited cell migration, and relieved LPS-induced inflammatory responses through the JAK/STAT signalling pathway.

9.
Nanoscale ; 16(35): 16451-16457, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39171723

RESUMEN

Through modulating the multidentate ligands, solvent environments, and inorganic tin precursors during the synthesis processes, we have successfully prepared a series of unprecedented heterometallic Sn-Ti oxo clusters with structural diversity and different physiochemical attributes. Initially, two Sn6Ti10 clusters were synthesized using trimethylolpropane as a structure-oriented ligand and SnCl4·5H2O as a tin source. Then, when a larger pentadentate ligand di(trimethylolpropane) was used instead of trimethylolpropane and aprotic acetonitrile solvent was introduced into the reaction system, four low-nuclearity Sn-Ti oxo clusters were discovered, including two Sn1Ti1, one Sn2Ti2 and one Sn2Ti6. Finally, two mixed-valence state clusters, SnII4SnIV2TiIV14 and SnII4SnIV4TiIV20, were obtained by transforming the tin precursor from SnCl4·5H2O to SnCl2·2H2O and adjusting the acetonitrile solution with trace acetic acid/formic acid. Sn8Ti20 is the highest-nuclearity heterometallic Sn-Ti oxo cluster to date. Moreover, comparative electrocatalytic CO2 reduction experiments were carried out, and it was concluded that the Sn8Ti20-decorated electrode showed the most satisfactory performance due to the influence of mixed-valence states of the Sn atoms and the charging effects provided by 20 Ti4+ ions. This study presents important guiding significance for the design, synthesis and application optimization of functional heterometallic nanoclusters.

10.
Front Psychol ; 15: 1276618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171240

RESUMEN

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's α = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations.

11.
Acad Radiol ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39174359

RESUMEN

RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3‰) in the 35-44 years age group and 25 (4.2‰) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.

12.
Animals (Basel) ; 14(16)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39199917

RESUMEN

This study investigated the effects of dietary energy levels during late gestation on mineral content in the plasma, colostrum, and milk of jennies postpartum. Twenty-four pregnant multiparous DeZhou jennies, aged 6.0 ± 0.1 years, with a body weight of 292 ± 33 kg, an average parity number of 2.7 ± 0.1, and similar expected dates of confinement (74 ± 4 days), were randomly allocated to three groups and fed three diets: high energy (12.54 MJ/kg, HE), medium energy (12.03 MJ/kg, ME), and low energy (11.39 MJ/kg, LE). Blood samples were collected from the jugular vein of each jenny at time points of 0 h, 24 h, 48 h, 5 d, 7 d, and 14 d after parturition. Additionally, milk samples were collected through manual milking, and an analysis of the mineral content was conducted. The results showed that compared with HE, both ME and LE significantly increased the levels of calcium (Ca), phosphorus (P), zinc (Zn), selenium (Se), molybdenum (Mo), and cobalt (Co) in the plasma and Ca, P, magnesium (Mg), copper (Cu), manganese (Mn), Zn, selenium (Se), molybdenum (Mo), and Co in the milk of jennies postpartum (p < 0.05); ME also increased the levels of potassium (K), iron (Fe), and Mn in plasma and K and Fe in milk (p < 0.05). The levels of Ca, K, Mg, P, Fe, Cu, Mn, Co, Se, Zn, and Mo in plasma and milk gradually decreased with increasing postpartum time. Their contents were the highest at 0 h postpartum, rapidly decreased after 24 h postpartum, and declined to the lowest on day 14 postpartum. The interaction between dietary energy level and postpartum time showed that although the concentrations of the minerals Ca, P, K, Mg, Fe, Cu, Mn, Zn, Co, Se, and Mo decreased in jennies' plasma and milk in the treatment groups with different energy levels as postpartum time increased, the pattern of change was also influenced by dietary energy level. The influence of dietary energy level in late gestation on the mineral content of milk and plasma during the postpartum colostrum phase was higher than that during the milk phase. In conclusion, this study demonstrated that, under the current experimental conditions, the mineral content of the colostrum, milk, and plasma of jennies after parturition was dependent on the dietary energy level during late gestation.

14.
Cancer Lett ; 600: 217161, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39117067

RESUMEN

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.


Asunto(s)
Autofagia , Plaquetas , Carcinoma Hepatocelular , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Animales , Humanos , Masculino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Plaquetas/metabolismo , Plaquetas/patología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Serina-Treonina Quinasas TOR/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética
15.
Int Immunopharmacol ; 141: 112863, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146779

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease that causes persistent inflammation involving the joints, cartilage, and synovium. In individuals with RA, alterations in the composition of intestinal bacteria suggest the vital role of gut microbiota in immune dysfunction. Multiple therapies commonly used to treat RA can also alter the diversity of gut microbiota, further suggesting the modulation of gut microbiota as a prevention or treatment for RA. Therefore, a better understanding of the changes in the gut microbiota that accompany RA should facilitate the development of novel therapeutic approaches. In this study, B. coagulans BACO-17 not only significantly reduced paw swelling, arthritis scores, and hind paw and forepaw thicknesses but also protected articular cartilage and the synovium against RA degeneration, with a corresponding downregulation of TNF-α expression. The inhibition or even reversing of RA progression highlights B. coagulans BACO-17 as a novel therapeutic for RA worth investigating.


Asunto(s)
Artritis Reumatoide , Bacillus coagulans , Progresión de la Enfermedad , Microbioma Gastrointestinal , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Membrana Sinovial/inmunología , Membrana Sinovial/patología , Membrana Sinovial/efectos de los fármacos , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos , Probióticos/uso terapéutico , Humanos , Ratones , Ratas , Condrocitos/efectos de los fármacos , Condrocitos/inmunología
16.
Eur J Pharmacol ; 982: 176900, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39168432

RESUMEN

Atrial fibrosis is associated with the occurrence of atrial fibrillation (AF) and regulated by the transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signalling pathway. Unfortunately, the mechanisms of regulation of TGF-ß1/Smad2/3-induced atrial fibrosis and vulnerability to AF remain still unknown. Previous studies have shown that sirtuin3 (SIRT3) sulfhydration has strong anti-fibrotic effects. We hypothesised that SIRT3 sulfhydration inhibits angiotensin II (Ang-II)-induced atrial fibrosis via blocking the TGF-ß1/Smad2/3 signalling pathway. In this study, we found that SIRT3 expression was decreased in the left atrium of patients with AF compared to that in those with sinus rhythm (SR). In vitro, SIRT3 knockdown by small interfering RNA significantly expanded Ang-II-induced atrial fibrosis and TGF-ß1/Smad2/3 signalling pathway activation, whereas supplementation with Sodium Hydrosulfide (NaHS, exogenous hydrogen sulfide donor and sulfhydration agonist) and SIRT3 overexpression using adenovirus ameliorated Ang-II-induced atrial fibrosis. Moreover, we observed suppression of the TGF-ß1/Smad2/3 pathway when Ang-II was combined with NaHS treatment, and the effect of this co-treatment was consistent with that of Ang-II combined with LY3200882 (Smad pathway inhibitor) on reducing atrial fibroblast proliferation and cell migration in vitro. Supplementation with dithiothreitol (DTT, a sulfhydration inhibitor) and adenovirus SIRT3 shRNA blocked the ameliorating effect of NaHS and AngII co-treatment on atrial fibrosis in vitro. Finally, continued treatment with NaHS in rats ameliorated atrial fibrosis and remodelling, and further improved AF vulnerability induced by Ang-II, which was reversed by DTT and adenovirus SIRT3 shRNA, suggesting that SIRT3 sulfhydration might be a potential therapeutic target in atrial fibrosis and AF.


Asunto(s)
Angiotensina II , Fibrilación Atrial , Fibrosis , Atrios Cardíacos , Sulfuro de Hidrógeno , Transducción de Señal , Sirtuina 3 , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Anciano , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Angiotensina II/farmacología , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Fibrilación Atrial/prevención & control , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Sirtuina 3/metabolismo , Sirtuina 3/genética , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
17.
Chemosphere ; 364: 143109, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39151579

RESUMEN

Sulfide biomineralization is a microorganism-induced process for transforming the environmentally hazardous cadmium into useful resource utilization. This study successfully constructed cadmium sulfide nanoparticles-Rhodopseudomonas palustris (Bio-CdS NPs-R. palustris) hybrids. For the self-assembling hybrids, Bio-CdS NPs were treated as new artificial-antennas to enhance photosynthesis, especially under low light (LL). Bacterial physiological results of hybrids were significantly increased, particularly for cells under LL, with higher enhancement photon harvesting ability. The enhancement included the pigment contents, and the ratio of the peripheral light-harvesting complex Ⅱ (LH2) to light-harvesting Ⅰ (1.33 ± 0.01 under LL), leading to the improvements of light-harvesting, transfer, and antenna conversion efficiencies. Finally, the stimulated electron chain of hybrids improved bacterial metabolism with increased nicotinamide adenine dinucleotide (NADH, 174.5% under LL) and adenosine triphosphate (ATP, 41.1% under LL). Furthermore, the modified photosynthetic units were induced by the up-regulated expression of fixK, which was activated by reduced oxygen tension of the medium for hybrids. fixK up-regulated genes encoding pigments (crt, and bch) and complexes (puf, pucAB, and pucC), leading to improved light-harvesting and transfer, and transform ability. This study provides a comprehensive understanding of the solar energy utilization mechanism of in-situ semiconductor-phototrophic microbe hybrids, contributing to further theoretical insight into their practical application.


Asunto(s)
Compuestos de Cadmio , Luz , Fotosíntesis , Rhodopseudomonas , Sulfuros , Sulfuros/química , Rhodopseudomonas/metabolismo , Compuestos de Cadmio/química , Biomineralización , Biodegradación Ambiental , Nanopartículas/química
18.
Pancreas ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39102586

RESUMEN

BACKGROUND: Assessment of the presence of choledocholithiasis is crucial among acute biliary pancreatitis (ABP). Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) are widely used to identify the gallstones of common bile duct (CBD). EUS provides better diagnostic accuracy and sensitivity than MRCP but carries a certain risk due to sedation. We investigated the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis for better selection of MRCP or EUS. METHODS: A total of 2321 ABP patients were retrospectively included in this study. Based on the exclusion criteria, 337 ABP patients with negative MRCP results were ultimately included. Among these patients, 75 patients had positive EUS findings. Univariate and multivariate logistic regression models were used to screen the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. RESULTS: Patients with positive EUS findings were older (62.0 vs. 55.0) and had higher rate of cholecystectomy history (18.7% vs. 7.3%) than those with negative EUS findings. The result of univariate logistic regression showed that the history of cholecystectomy, age and sex were potential risk factors (all p < 0.05). Then after adjusting the other potential risk factors (Direct bilirubin (DBIL), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP)), a history of cholecystectomy (OR = 2.859 [1.312,6.23]), older age (1.03 [1.009,1.052]) and male (2.016 [1.152,3.528]) were independent risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. CONCLUSIONS: The history of cholecystectomy, older age and male are independently associated with an increased risk of negative diagnosis of MRCP in ABP patients with choledocholithiasis. We suggest that patients with these risk factors should undergo EUS first, rather than MRCP.

19.
Shanghai Kou Qiang Yi Xue ; 33(3): 279-284, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39104344

RESUMEN

PURPOSE: To study the clinical efficacy of small intestinal submucosa (SIS) absorbable biological membrane in alveolar bone defect repair. METHODS: A total of 102 patients with alveolar bone defect who received guided bone regeneration (GBR) in our hospital from January 2020 to January 2022 were selected and divided into Bio-Gide group (51 cases using Bio-Gide absorbable biofilm) and SIS group (51 cases using SIS absorbable biofilm) by computer random number generator. The perioperative related indicators, blood calcium, blood phosphorus, biocompatibility, periodontal attachment loss (PAL) length, pulp sensitivity, tooth mobility, alveolar bone volume and adverse events of the two groups were compared. Statistical analysis was performed with SPSS 24.0 software package. RESULTS: There was no significant difference in operation time, intraoperative blood loss, visual analogue scale (VAS) score of pain on the first day after operation, VAS score on the fifth day after operation, wound healing time, blood calcium and phosphorus levels before operation, 1 d and 12 d after operation, PAL length before operation, 3 months, 6 months and 12 months after operation, pulp sensitivity and tooth looseness grade 1 and 2 percentage at 3, 6 and 12 months after operation, bone width increase, bone height increase at 12 months after operation and adverse event rate between the two groups (P>0.05). Compared with Bio-Gide group, the wound healing time and biofilm absorption time were shortened in SIS group(P<0.05), and the incidence of rejection was decreased 12 d after operation (P<0.05). CONCLUSIONS: SIS absorbable biofilm and Bio-Gide absorbable biofilm have similar efficacy and safety in repairing GBR for alveolar bone defects, but the former is more biocompatible and the latter can provide longer barrier function.


Asunto(s)
Biopelículas , Mucosa Intestinal , Humanos , Pérdida de Hueso Alveolar , Regeneración Ósea , Intestino Delgado , Implantes Absorbibles
20.
ACS Omega ; 9(32): 35197-35208, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39157101

RESUMEN

A series of minimally sized regular dodecahedron-embedded metallofullerene REC20 clusters (RE = Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Eu, and Gd) as basic units of nanoassembled materials with tunable magnetism and UV sensitivity have been explored using density functional theory (DFT). The contribution of the 4f orbital of the rare earth atom at the center of the C20 cage to the frontier molecular orbital of REC20 gives the REC20 cluster additional stability. The AdNDP orbitals of the four REC20 superatoms that conform to the spherical jellium model indicate that through natural population analysis and spin density diagrams, we observe a monotonic increase in the magnetic moment from Ce to Gd. This is attributed to the increased number of unpaired electrons in the 4f orbitals of lanthanide rare earth atoms. The UV-visible spectrum of REC20 clusters shows strong absorption in the mid-UV and near-UV bands. REC20 clusters encapsulating lanthanide rare earth atoms stand out for their tunable magnetism, UV sensitivity, and stability, making them potential new self-assembly materials.

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