Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 332
Filtrar
1.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39000510

RESUMEN

Poplar coma, the fluff-like appendages of seeds originating from the differentiated surface cells of the placenta and funicle, aids in the long-distance dispersal of seeds in the spring. However, it also poses hazards to human safety and causes pollution in the surrounding environment. Unraveling the regulatory mechanisms governing the initiation and development of coma is essential for addressing this issue comprehensively. In this study, strand-specific RNA-seq was conducted at three distinct stages of coma development, revealing 1888 lncRNAs and 52,810 mRNAs. The expression profiles of lncRNAs and mRNAs during coma development were analyzed. Subsequently, potential target genes of lncRNAs were predicted through co-localization and co-expression analyses. Integrating various types of sequencing data, lncRNA-miRNA-TF regulatory networks related to the initiation of coma were constructed. Utilizing identified differentially expressed genes encoding kinesin and actin, lncRNA-miRNA-mRNA regulatory networks associated with the construction and arrangement of the coma cytoskeleton were established. Additionally, relying on differentially expressed genes encoding cellulose synthase, sucrose synthase, and expansin, lncRNA-miRNA-mRNA regulatory networks related to coma cell wall synthesis and remodeling were developed. This study not only enhances the comprehension of lncRNA but also provides novel insights into the molecular mechanisms governing the initiation and development of poplar coma.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , MicroARNs , Populus , ARN Largo no Codificante , ARN Mensajero , Populus/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , MicroARNs/genética , Perfilación de la Expresión Génica/métodos , Semillas/genética , Semillas/crecimiento & desarrollo
2.
Acta Trop ; 257: 107320, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39002739

RESUMEN

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

3.
Redox Biol ; 75: 103268, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39032396

RESUMEN

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

4.
Risk Manag Healthc Policy ; 17: 1239-1251, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765781

RESUMEN

Introduction: Traditional Chinese medicine (TCM) holds great potential in promoting healing and relieving pain for herpes zoster (HZ) treatments. Evidence showed that both healthcare professionals' (HCPs) belief and knowledge influence their attitudes, which result in their expression and direct behavior. However, little is known in this area regarding TCM treatments for HZ. This study aimed to understand the HCPs' perceptions, attitudes, beliefs, and practices toward TCM and its services for HZ. Methods: During July 2021 and October 2022, a cross-sectional study of HCPs querying demographics, perceptions, attitudes, beliefs, and practices toward TCM and TCM services for HZ was conducted. The frequency and percentage or mean and standard deviation were used to present categorical data and continuous data, respectively. A Chi-square analysis compared nurses' and doctors' views on TCM treatments for HZ. Results: Out of 306 eligible respondents, 66.0% used TCM content in clinical practice less than 40% of the time. Respondents reported that there were three main advantages of TCM for HZ, including better crusting and healing, fewer side effects, and mitigating complications. A total of 41.3% (81/196) of the respondents who had cared for/treated HZ patients applied TCM treatments. The three factors most associated with referrals/providing TCM to patients were postherpetic neuralgia, early erythema or papules, and acute pain. Compared to nurses, doctors showed more endorsement of the efficacy and cost-effectiveness of TCM treatments for HZ patients. Conclusion: The study found that most healthcare professionals in HZ had a favorable view of TCM, but lacked practical experience administering it to patients. Programs should be developed to provide evidence-based TCM treatments and encourage combining TCM with Western medicine for better patient care.

5.
Front Immunol ; 15: 1404828, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745647

RESUMEN

Objectives: Interstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS). Methods: Here, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately. Results: Peripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/µL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/µL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS. Conclusions: Patients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD.


Asunto(s)
Progresión de la Enfermedad , Células Asesinas Naturales , Enfermedades Pulmonares Intersticiales , Miositis , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Células Asesinas Naturales/inmunología , Miositis/inmunología , Miositis/sangre , Miositis/diagnóstico , Pronóstico , Anciano , Estudios Prospectivos , Adulto , Depleción Linfocítica , Helicasa Inducida por Interferón IFIH1/inmunología , Factores de Riesgo , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/inmunología , Recuento de Linfocitos , Estudios Longitudinales
6.
Sci Adv ; 10(14): eadk8093, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578989

RESUMEN

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.


Asunto(s)
Vacuna BCG , Tuberculosis , Humanos , Ácido Linoleico , Inmunidad Entrenada , Multiómica , Adyuvantes Inmunológicos/farmacología
7.
Mitochondrial DNA B Resour ; 9(2): 304-308, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414806

RESUMEN

Whether Barbella flagellifera (Cardot) Nog. belongs to Neodicladiella has not yet been determined, and a study of the complete chloroplast (cp) genome of B. flagellifera would aid in determining its evolutionary position. In this study, we aimed to sequence the complete cp genome of B. flagellifera, an epiphytic species found in tropical and subtropical forests. The complete cp genome is 125,025 base pairs (bp) long and appears as a typical quadrilateral structure with a large single-copy (86,854 bp), a small single-copy (18,473 bp), and a pair of inverted repeats (19,698 bp). The overall GC content of the sequence is 41.0% and the genome encodes 127 genes, including 82 protein-coding genes, 37 tRNAs, and eight rRNAs. Phylogenetic analysis reveals that B. flagellifera clustered into a clade with other Hypnales groups with high bootstrap support. The complete cp genome presented here will provide helpful information for species identification of Barbella genus and Neodicladiella genus in Meteoriaceae.

8.
Biomaterials ; 306: 122483, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38330742

RESUMEN

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".


Asunto(s)
Osteoartritis , Factores de Transcripción , Animales , Humanos , Ratones , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/metabolismo , Inflamación/metabolismo , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Osteoartritis/metabolismo , Membrana Sinovial/metabolismo , Factores de Transcripción/metabolismo
9.
J Mol Neurosci ; 74(1): 24, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38386166

RESUMEN

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.


Asunto(s)
Glutatión Transferasa , Accidente Cerebrovascular Hemorrágico , Animales , Ratones , Antioxidantes , Hemorragia Cerebral/genética , Modelos Animales de Enfermedad , Glutatión , Glutatión Transferasa/genética , Hemina/farmacología , Neuronas , ARN Mensajero
10.
Am J Hum Genet ; 111(3): 594-613, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38423010

RESUMEN

The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile). In patient-derived fibroblasts, bi-allelic SNF8 variants cause loss of ESCRT-II subunits. Snf8 loss of function in zebrafish results in global developmental delay and altered embryo morphology, impaired optic nerve development, and reduced forebrain size. In vivo experiments corroborated the pathogenicity of the tested SNF8 variants and their variable impact on embryo development, validating the observed clinical heterogeneity. Taken together, we conclude that loss of ESCRT-II due to bi-allelic SNF8 variants is associated with a spectrum of neurodevelopmental/neurodegenerative phenotypes mediated likely via impairment of the autophagic flux.


Asunto(s)
Epilepsia Generalizada , Atrofia Óptica , Animales , Humanos , Niño , Pez Cebra/genética , Atrofia Óptica/genética , Fenotipo , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética
11.
Cell Res ; 34(3): 183-184, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38228880
12.
J Cancer ; 15(4): 889-907, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38230219

RESUMEN

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

13.
Adv Biol (Weinh) ; 8(3): e2300510, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38085135

RESUMEN

Brown adipose tissue undergoes rapid postnatal development to mature and plays a crucial role in thermoregulation and energy expenditure, which protects against cold and obesity. Herein, it is shown that the expression of Trim21 mRNA level of interscapular brown adipose tissue elevates after birth, and peaks at P14 (postnatal day 14). Trim21 depletion severely impairs the maturation of interscapular brown adipose tissue, decreases the expression of a series of thermogenic genes, and reduces energy expenditure. Consistently, the loss of Trim21 also leads to a suppression of white adipose tissue "browning", in response to cold exposure and a ß-adrenergic agonist, CL316,243. In addition, Trim21-/- mice are more prone to high-fat diet-induced obesity compared with the control littermates. Taken together, the study for the first time reveals a critical role of Trim21 in regulating iBAT postnatal development and thermogenesis.


Asunto(s)
Tejido Adiposo Pardo , Tejido Adiposo Blanco , Animales , Ratones , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Metabolismo Energético/genética , Obesidad/genética , Obesidad/metabolismo , Termogénesis/genética
15.
Front Public Health ; 11: 1297472, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38125844

RESUMEN

Objective: This study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate. Methods: Data on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed. Results: The deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% (p = 0.000, 95%CI: 12.14-13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92-5.53%), BP 3.30% (3.06-3.55%), and Hb 2.92% (2.68-3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate (p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals (p < 0.05). Logistic regression showed that sex, blood donation history, sleep quality, diet and mental status were independent risk factors for ALT deferral (p < 0.05), with odds ratios (ORs) of 5.057, 2.735, 1.594, 3.679, and 1.957, respectively. Age, blood donation history, sleep quality and mental state were independent risk factors for BP deferral (p < 0.05), with ORs of 0.256, 3.658, 6.042, and 1.812, respectively. Gender, blood donation history and diet were independent risk factors for Hb deferral (p < 0.05), with ORs of 0.244, 0.542, and 3.103, respectively. Conclusion: Students' health problems require attention. Effective health education should improve self-health management and pre-donation health behaviour to encourage regular blood donation.


Asunto(s)
Donación de Sangre , Donantes de Sangre , Humanos , Estudios Retrospectivos , Hemoglobinas/análisis , Estudiantes , Composición Familiar , Estilo de Vida
16.
Bone Res ; 11(1): 56, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884520

RESUMEN

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21-/-) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21-/- and Ctsk-cre; Trim21f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/ß-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.


Asunto(s)
Osteogénesis , Osteoporosis , Animales , Femenino , Humanos , Ratones , beta Catenina/genética , Huesos/metabolismo , Diferenciación Celular/genética , Osteogénesis/genética , Osteoporosis/genética
17.
J Geriatr Cardiol ; 20(8): 577-585, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37675263

RESUMEN

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS: The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

18.
Dentomaxillofac Radiol ; 52(7): 20230051, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37395620

RESUMEN

OBJECTIVE: Pre-operative differentiation between pleomorphic adenoma (PA) and Warthin's tumor (WT) of the major salivary glands is crucial for treatment decisions. The purpose of this study was to develop and validate a nomogram incorporating clinical, conventional ultrasound (CUS) and shear wave elastography (SWE) features to differentiate PA from WT. METHODS: A total of 113 patients with histological diagnosis of PA or WT of the major salivary glands treated at Fujian Medical University Union Hospital were enrolled in training cohort (n = 75; PA = 41, WT = 34) and validation cohort (n = 38; PA = 22, WT = 16). The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening the most optimal clinical, CUS, and SWE features. Different models, including the nomogram model, clinic-CUS (Clin+CUS) and SWE model, were built using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts, and then compared among the three models. RESULTS: The nomogram incorporating the clinical, CUS and SWE features showed favorable predictive value for differentiating PA from WT, with the area under the curves (AUCs) of 0.947 and 0.903 for the training cohort and validation cohort, respectively. Decision curve analysis showed that the nomogram model outperformed the Clin+CUS model and SWE model in terms of clinical usefulness. CONCLUSIONS: The nomogram had good performance in distinguishing major salivary PA from WT and held potential for optimizing the clinical decision-making process.


Asunto(s)
Adenolinfoma , Adenoma Pleomórfico , Diagnóstico por Imagen de Elasticidad , Humanos , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/patología , Nomogramas , Glándulas Salivales , Adenolinfoma/diagnóstico por imagen
19.
ACS Omega ; 8(28): 24922-24930, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37483218

RESUMEN

Nitrate is a contaminant widely found in surface water, and a high concentration of nitrate can pose a serious threat to human health. Zero-valent iron is widely used to reduce nitrate in aqueous solution, but an acidic condition is required. Zero-valent aluminum has a much lower redox potential (E0(Al3+/Al0) = -1.662 V) than zero-valent iron (E0(Fe2+/Fe0) = -0.44 V), making it a better choice for reduction of nitrate. However, a passive oxide film covering on Al surfaces inhibits its electron transfer. In this work, metal Al powder was activated by a soaking procedure in deionized water. It was found that nitrate in neutral solution can be efficiently and completely reduced by soaked Al, even if the concentration of nitrate-N was up to 100 mg L-1. Using an optimal soaking time, the soaked Al can remove >90% of nitrate in aqueous solution within ∼2 h at 50 °C. Furthermore, the nitrate reduction efficiency increased with increasing reaction temperature and dosage of Al powder. After reaction, only ∼50% of pristine N content was left in the form of ammonia ions (NH4+) in aqueous solution. Mechanism analyses showed that after soaking, Al particle surfaces were covered by a layer of loose and fine Al(OH)3 grains, which can shorten the induction time for the beginning of the reaction between inner Al and outside ions or molecules. This is the reason why soaked Al has a high efficiency for nitrate removal. The present results indicate that soaking is an effective way to activate Al to remove nitrate in water.

20.
Environ Sci Pollut Res Int ; 30(39): 90980-90992, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37468774

RESUMEN

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.


Asunto(s)
Mercurio , Femenino , Embarazo , Humanos , Estudios Transversales , China , Mercurio/análisis , Factores de Riesgo , Conducta Alimentaria
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...