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1.
World J Psychiatry ; 14(6): 794-803, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38984340

RESUMEN

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

2.
Front Public Health ; 12: 1368401, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952728

RESUMEN

Objective: To investigate the association between dietary and some other environmental factors and the risk of inflammatory bowel diseases (IBD) in Chinese population. Materials and methods: A multicenter case-control study was conducted involving 11 hospitals across China. A total of 1,230 subjects were enrolled consecutively, and diet and environmental factor questionnaires were collected. IBD patients were matched with healthy controls (HC) using propensity-score matching (PSM) at a 1:1 ratio with a caliper value of 0.02. Multivariate conditional logistic regression analyses were performed to evaluate the associations between diet, environmental factors, and IBD. Results: Moderate alcohol and milk consumption, as well as daily intake of fresh fruit, were protective factors for both Crohn's disease (CD) and ulcerative colitis (UC). Conversely, the consumption of eggs and chocolate increased the risk of IBD. Outdoor time for more than 25% of the day was a protective factor only for CD. In eastern regions of China, CD patients had higher egg consumption and less outdoor time, while UC patients consumed more chocolate. IBD patients from urban areas or with higher per capita monthly income consumed more fruit, eggs, and chocolate. Conclusions: This study reveals an association between specific foods, outdoor time, and the emergence of IBD in the Chinese population. The findings emphasize the importance of a balanced diet, sufficient outdoor time and activities, and tailored prevention strategies considering regional variations.


Asunto(s)
Dieta , Enfermedades Inflamatorias del Intestino , Puntaje de Propensión , Humanos , China/epidemiología , Femenino , Estudios de Casos y Controles , Masculino , Adulto , Dieta/estadística & datos numéricos , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología
3.
J Am Chem Soc ; 146(28): 18899-18904, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38975975

RESUMEN

In recent years, dysprosium macrocycle single-molecule magnets (SMMs) have received increasing attention due to their excellent air/thermal stability, strong magnetic anisotropy, and rigid molecular skeleton. However, they usually display fast zero-field quantum tunneling of the magnetization (QTM) rate, severely hindering their data storage applications. Herein, we report the design, synthesis, and characterization of an air-stable monodecker didysprosium macrocycle integrating strong single-ion anisotropy, near-perfect local crystal field (CF) symmetry, and efficient exchange bias. These indispensable features enable clear-cut elucidation of the crucial role of very weak antiferromagnetic coupling on magnetization dynamics, creating a prominent SMM with a large effective energy barrier (Ueff) of 670 cm-1, open hysteresis loops at zero field up to 14.9 K, and a record relaxation time of QTM (τQTM), 24281 s, for all known nonradical-bridged lanthanide SMMs.

4.
J Orthop Traumatol ; 25(1): 32, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926180

RESUMEN

BACKGROUND: Lumbar-iliac fixation (LIF) is a common treatment for Tile C1.3 pelvic fractures, but different techniques, including L4-L5/L5 unilateral LIF (L4-L5/L5 ULIF), bilateral LIF (BLIF), and L4-L5/L5 triangular osteosynthesis (L4-L5/L5 TOS), still lack biomechanical evaluation. The sacral slope (SS) is key to the vertical shear of the sacrum but has not been investigated for its biomechanical role in lumbar-iliac fixation. The aim of this study is to evaluate the biomechanical effects of different LIF and SS on Tile C1.3 pelvic fracture under two-legged standing load in human cadavers. METHODS: Eight male fresh-frozen human lumbar-pelvic specimens were used in this study. Compressive force of 500 N was applied to the L4 vertebrae in the two-legged standing position of the pelvis. The Tile C1.3 pelvic fracture was prepared, and the posterior pelvic ring was fixed with L5 ULIF, L4-L5 ULIF, L5 TOS, L4-L5 TOS, and L4-L5 BLIF, respectively. Displacement and rotation of the anterior S1 foramen at 30° and 40° sacral slope (SS) were analyzed. RESULTS: The displacement of L4-L5/L5 TOS in the left-right and vertical direction, total displacement, and rotation in lateral bending decreased significantly, which is more pronounced at 40° SS. The difference in stability between L4-L5 and L5 ULIF was not significant. BLIF significantly limited left-right displacement. The ULIF vertical displacement at 40° SS was significantly higher than that at 30° SS. CONCLUSIONS: This study developed an in vitro two-legged standing pelvic model and demonstrated that TOS enhanced pelvic stability in the coronal plane and cephalad-caudal direction, and BLIF enhanced stability in the left-right direction. L4-L5 ULIF did not further improve the immediate stability, whereas TOS is required to increase the vertical stability at greater SS.


Asunto(s)
Cadáver , Fijación Interna de Fracturas , Fracturas Óseas , Vértebras Lumbares , Huesos Pélvicos , Sacro , Humanos , Masculino , Huesos Pélvicos/lesiones , Fenómenos Biomecánicos , Sacro/lesiones , Sacro/cirugía , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Vértebras Lumbares/fisiopatología , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Ilion , Persona de Mediana Edad , Anciano
5.
J Exp Clin Cancer Res ; 43(1): 160, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38840183

RESUMEN

BACKGROUND: The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate. METHODS: To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction. RESULTS: Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression. CONCLUSIONS: In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Invasividad Neoplásica , Neovascularización Patológica , Tetraspanina 24 , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Tetraspanina 24/metabolismo , Tetraspanina 24/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Ratones , Animales , Línea Celular Tumoral , Masculino , Femenino , Movimiento Celular , Angiogénesis
6.
Stem Cell Res ; 77: 103428, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38696853

RESUMEN

Peripheral blood mononuclear cells (PBMCs) from a 28-year-old male patient with unipolar depression were reprogrammed with reprogramming factors by electroporation. The pluripotency of transgene-free induced pluripotent stem cells (iPSCs) was verified by immunofluorescence staining for pluripotency markers, and these iPSCs were able to differentiate into the 3 germ layers in vitro. These iPSCs also showed normal karyotypes. Thus, we believe that these iPSCs could be valuable models for exploring the underlying biological mechanism of depression and the safety of antidepressants through the use of iPSCs differentiated into different kinds of neurons or brain organoids.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Humanos , Masculino , Células Madre Pluripotentes Inducidas/metabolismo , Adulto , Depresión , Línea Celular , Reprogramación Celular , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/citología
7.
Surg Endosc ; 38(7): 3773-3782, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38789624

RESUMEN

BACKGROUND: Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL). METHODS: Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist. RESULTS: In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30 days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0 days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5 days, p = 0.005) compared to sclerotherapy alone. CONCLUSION: Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL.


Asunto(s)
Hemorragia Gastrointestinal , Hemostasis Endoscópica , Escleroterapia , Humanos , Escleroterapia/métodos , Masculino , Femenino , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Persona de Mediana Edad , Anciano , Hemostasis Endoscópica/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Adulto , Recurrencia
8.
Artículo en Inglés | MEDLINE | ID: mdl-38657895

RESUMEN

Bipolar disorder (BD) is a complex, severe mental illness with cognitive impairment. Impairments in attention and memory are particularly evident. A large number of previous studies have identified CACNA1C and ANK3 gene variants as risk factors for BD and both affect cognitive function in people with BD. However, it is unclear whether there is an interaction effects between the two genes on cognitive impairment in patients. We used 153 Chinese Han Chinese patients with BD to explore the association of CACNA1C and ANK3 variants with attention and immediate memory using Plink software and and performed a epistatic interaction effects analysis. We found that CACNA1C and ANK3 gene variants respectively affected patients' scores on attention and memory tests. The significant SNP in the CACNA1C and ANK3 genes are rs73042126(P = 3.16 × 10-5,FDR = 0.0253) and rs2393640(P = 1.50 × 10-4,FDR = 0.0353) respectively. And they also interacted to affect cognitive functioning in BD patients (attention: P = 0.0289; immediate memory: P = 0.0398). Follow-up studies should increase the sample size, improve the assessment methods and experimental design, and further explore the pathogenic mechanisms of BD.


Asunto(s)
Ancirinas , Trastorno Bipolar , Canales de Calcio Tipo L , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ancirinas/genética , Atención/fisiología , Trastorno Bipolar/genética , Trastorno Bipolar/psicología , Canales de Calcio Tipo L/genética , Cognición , Disfunción Cognitiva/genética , Memoria a Corto Plazo , Pruebas Neuropsicológicas , Pueblos del Este de Asia/genética
9.
J Ethnopharmacol ; 328: 118124, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38556138

RESUMEN

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.


Asunto(s)
Escitalopram , Morinda , Ratones , Animales , Depresión/tratamiento farmacológico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Oligosacáridos/farmacología , Oligosacáridos/uso terapéutico , Inflamación/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Modelos Animales de Enfermedad
10.
Surg Endosc ; 38(4): 1877-1883, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38307960

RESUMEN

BACKGROUND: Endoscopic submucosal dissection (ESD) was widely used for the removal of esophageal tumors, and post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was one of the postoperative adverse events. The aim of this research was to develop and validate a model to predict electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors. MATERIALS AND METHODS: Patients who underwent esophageal ESD in our hospital were retrospectively included. A predictive nomogram was established based on the results of multivariate logistic regression analysis, and bootstrapping resampling was used for internal validation. Besides, the clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA) and clinical impact curve. RESULTS: A total of 552 patients who underwent esophageal ESD were included in the study, and the incidence of PPECS was 12.5% (69/552). Risk factors associated with PEECS (p < 0.1) were analyzed by multivariate logistic regression analysis, and the final model included four variables, namely gender, diabetes, tumor size and operation time. The predictive nomogram was constructed based on the above four variables, and the area under the ROC curve (AUC) was 0.811 (95% CI 0.767-0.855). The calibration curve of the nomogram presented good agreement between the predicted and actual probabilities. DCA showed that the model improved patient outcomes by helping to assess the risk of PEECS in patients compared to an all-or-no treatment strategy. In addition, the clinical impact curve of the model also indicates that the nomogram has a high clinical net benefit. CONCLUSION: In conclusion, we have developed a predictive nomogram for PEECS after ESD for esophageal tumors with good predictive accuracy and discrimination. This predictive nomogram can be effectively used to identify high-risk patients with PEECS, which will help clinicians in clinical decision-making and early intervention.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Humanos , Nomogramas , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Neoplasias Esofágicas/patología , Electrocoagulación/efectos adversos
11.
Heliyon ; 10(4): e25748, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38384516

RESUMEN

Introduction: Fever is one of the postoperative complications of endoscopic submucosal dissection (ESD) and its derivative technology. However, there are few studies on risk factors for fever after ESD and its derivative technology. The aim of this study was to determine the incidence and related risk factors after ESD and its derivative technology for gastric lesions. Materials and methods: A retrospective review of patients with gastric lesions who were treated by ESD and its derivative technology in our hospital from January 2014 to January 2019 was conducted. Results: A total of 1955 patients were included in the present study. A total of 451 (23.1 %) patients presented with fever after ESD and its derived techniques. The highest fever temperature was 37.6 ± 3.12 °C, and the number of days with fever was 1.48 ± 0.85. Through single factor and multiple factor analysis, age (OR: 1.261, 95% CI: 1.009-1.576, p < 0.05), procedure time (OR: 1.457, 95% CI: 1.053-2.016, p < 0.05), postoperative gastric tube placement (OR: 2.098, 95% CI: 1:616-2.723, p < 0.05), intraoperative hemorrhage (OR: 1.537, 95% CI: 1.196-1.974, p < 0.05) and perforation (OR: 1.970, 95% CI: 1.531-2.535, p < 0.05) were independent risk factors for postoperative fever. Conclusion: Age ≥56 years old, procedure time ≥60 min, gastric tube placement, intraoperative hemorrhage and perforation were independent risk factors for postoperative fever after gastric ESD and its derivative technology. Attention should be given to such patients to minimize the risk of postoperative fever.

12.
Food Chem ; 441: 138361, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38199112

RESUMEN

Trimethylamine (TMA) is an organic amine with strong pungent smell which is an indicator gas for evaluating fish freshness according to the international standard. In this work, as-synthesize α-Fe2O3 solid nanocubes (NCs), α-Fe2O3 nucleoshell NCs and α-Fe2O3 hollow NCs were used as sensing material to develop an outstanding TMA gas sensor. The response of the α-Fe2O3 hollow NCs sensors towards 20 ppm TMA at 230 ℃ was 6.3. Meanwhile, these sensors showed exceptional response/recovery time, low limit of detection, great selectivity, and outstanding linear relationship. Furthermore, the analysis of gases released during the decomposition of Carassius auratus (0-10 days) was conducted, which demonstrated the assessment of TMA by α-Fe2O3 hollow NCs sensor can evaluate the freshness of Carassius auratus. Such a novel sensor signifies the outstanding application potential in efficient gas-sensing properties of TMA, which will make the tremendous contribution for Carassius auratus product evaluation in the future.


Asunto(s)
Carpas , Carpa Dorada , Metilaminas , Animales , Estudios de Factibilidad , Gases
13.
Surg Endosc ; 38(4): 1791-1806, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38291159

RESUMEN

BACKGROUND: Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. METHODS: We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. RESULTS: A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). CONCLUSIONS: Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.


Asunto(s)
Hemostasis Endoscópica , Hemostáticos , Úlcera Péptica , Humanos , Úlcera/complicaciones , Úlcera/terapia , Estudios Retrospectivos , Úlcera Péptica Hemorrágica/etiología , Endoscopía Gastrointestinal/efectos adversos , Hemostasis Endoscópica/efectos adversos , Úlcera Péptica/complicaciones , Recurrencia
14.
Small ; 20(25): e2307247, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38243871

RESUMEN

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.


Asunto(s)
Sistemas CRISPR-Cas , Lípidos , Morus , Nanopartículas , Hojas de la Planta , Nanopartículas/química , Hojas de la Planta/química , Animales , Administración Oral , Morus/química , Lípidos/química , Ratones , Enfermedades del Colon/terapia , Humanos , Masculino , Liposomas
15.
J Nanobiotechnology ; 22(1): 4, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38169394

RESUMEN

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Morus , Nanopartículas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Hojas de la Planta
16.
Adv Mater ; 36(14): e2309516, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38085512

RESUMEN

The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR) is constructed. Under near-infrared irradiation, the resultant P127-AuS@CURs generate transient mild photothermia (TMP; ≈42 °C, 10 min), which facilitates their penetration through colonic mucus and favors multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieves intracellular oxidative stress, improves wound healing, and reduces immune responses by polarizing the proinflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intralumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevates the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites can also mitigate colitis symptoms by regulating genes associated with antioxidation, anti-inflammation, and wound healing. Overall, the intestinal intralumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Curcumina , Nanopartículas , Humanos , Nanomedicina , Colitis/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Curcumina/farmacología , Antiinflamatorios/uso terapéutico , Membrana Mucosa/metabolismo
17.
PhytoKeys ; 235: 129-136, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38058552

RESUMEN

As a primary source of anticancer camptothecin, Camptotheca (Nyssaceae) is an economically valuable genus and has long been recorded as endemic to China. Here, Camptotheca is reported as a new record to the flora of Vietnam with the discovery of a wild population of C.acuminata from Lai Chau Province of northern Vietnam. Based on the consultation of relevant literature and type specimens of C.acuminata, a lectotype of the species is designated. Photographic illustrations, morphological description and a distribution map of C.acuminata is provided, and a key to all known species of Nyssaceae in Vietnam is presented, too.

18.
Ann Med ; 55(2): 2243988, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37669097

RESUMEN

BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.


Asunto(s)
Infecciones por Helicobacter , Neoplasias Gástricas , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , China/epidemiología , Prevalencia , Factores de Riesgo , Helicobacter pylori , Infecciones por Helicobacter/complicaciones , Detección Precoz del Cáncer , Humanos , Adulto , Persona de Mediana Edad , Anciano , Masculino , Femenino
19.
Science ; 381(6663): 1205-1211, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37708281

RESUMEN

Learning is highly important for edge intelligence devices to adapt to different application scenes and owners. Current technologies for training neural networks require moving massive amounts of data between computing and memory units, which hinders the implementation of learning on edge devices. We developed a fully integrated memristor chip with the improvement learning ability and low energy cost. The schemes in the STELLAR architecture, including its learning algorithm, hardware realization, and parallel conductance tuning scheme, are general approaches that facilitate on-chip learning by using a memristor crossbar array, regardless of the type of memristor device. Tasks executed in this study included motion control, image classification, and speech recognition.

20.
BMC Psychiatry ; 23(1): 692, 2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37743466

RESUMEN

BACKGROUND: Schizophrenia was clinically documented to co-occur with fractures and aberrant bone mineral density (BMD), but the potential causal relationship remained unclear. This study aimed to test the causal effects between schizophrenia and fractures as well as aberrant BMD by conducting Mendelian randomization (MR) analyses. METHODS: Two-sample MR was utilized, based on instrumental variables from large genome-wide association studies (GWAS) of schizophrenia as exposure, to identify the causal association of schizophrenia with mixed fractures, fractures at different body sites (including skull and facial bones, shoulder and upper arm, wrist and hand, and femur) and BMDs of forearm (FA), femoral neck (FN), lumbar spine (LS) and estimated BMD (eBMD). Multivariable Mendelian randomization (MVMR) analysis was performed to minimize the confounding effect of body mass index (BMI). RESULTS: Result from inverse variance weighting (IVW) method provided evidence schizophrenia increased the risk of fractures of skull and facial bones [odds ratio (OR) = 1.0006, 95% confidence interval (CI): 1.0003 to 1.0010] and femur [OR =1.0007, 95% CI: 1.0003 to 1.0011], whereas, decreased the level of eBMD [ß (95%CI): -0.013 (-0.021, -0.004)]. These causal effects still existed after adjusting for BMI. Sensitivity analyses showed similar results. However, no causal effect of schizophrenia on fracture or BMD in other parts was detected. CONCLUSION: The current finding confirmed that schizophrenia was causally associated with the fractures of skull, face and femur as well as eBMD, which might remind psychiatrists to pay close attention to the fracture risk in schizophrenic patients when formulating their treatment strategies.


Asunto(s)
Fracturas Óseas , Esquizofrenia , Humanos , Densidad Ósea/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Esquizofrenia/complicaciones , Esquizofrenia/genética , Fracturas Óseas/genética
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