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1.
Hematology ; 29(1): 2372482, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38994874

RESUMEN

BACKGROUND: CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear. AIM: To explore the relationship between CD83 and CD4+ T cell subsets and clarify the role of CD83 in the pathogenesis of ITP. METHODS: RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4+ T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression. RESULTS: The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4+ T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-ß, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression. CONCLUSION: The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients.


Asunto(s)
Antígenos CD , Antígeno CD83 , Inmunoglobulinas , Glicoproteínas de Membrana , Púrpura Trombocitopénica Idiopática , Humanos , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/patología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Antígenos CD/metabolismo , Inmunoglobulinas/genética , Inmunoglobulinas/metabolismo , Femenino , Masculino , Adulto , Persona de Mediana Edad , Citocinas/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo
2.
Wideochir Inne Tech Maloinwazyjne ; 19(2): 152-159, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38973789

RESUMEN

Aim: The aim of the article was to systematically evaluate the clinical efficacy and safety of transanal endoscopic microsurgery (TEM) and endoscopic submucosal dissection (ESD) in the treatment of rectal tumors. Material and methods: Control studies were conducted on cases included in the electronic databases Medline, Embase, Cochrane Library, and CNKI. Patients with colorectal tumors were included in the TEM and ESD groups for treatment, with the main indicators being R0 resection rate, postoperative perforation and bleeding incidence, and tumor recurrence rate. The meta-analysis was carried out using RevMan 5.3 software. Results: A total of 10 studies were included, with 736 patients. The analysis showed that for the recurrence rate in the TEM group compared to ESD, OR = 1.23, 95% CI = 0.56-2.72, p = 0.60; for the R0 resection rate between the TEM group and ESD group, OR = 1.35, 95% CI = 0.82-2.22, p = 0.24; for the incidence of perforation in the TEM and ESD groups, OR = 0.59, 95% CI = 0.25-1.40, p = 0.23. The inter-group comparison of these three items was statistically significant. Compared with the ESD group, the hospitalization time and the incidence of bleeding of the TEM group were both lower, with SD = 0.48, 95% CI = 0.26-0.69, p < 0.001 and OR = 0.35, 95% CI = 0.13-0.92, p = 0.03. The differences were statistically significant. Conclusions: Both TEM and ESD endoscopic treatment techniques can achieve a higher R0 resection rate and lower risk of tumor recurrence in the treatment of colorectal tumors. However, TEM may have higher surgical safety than ESD technology, and can shorten postoperative hospitalization time and lower postoperative bleeding rate.

3.
World J Oncol ; 15(4): 648-661, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38993258

RESUMEN

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

4.
BMJ Open Diabetes Res Care ; 12(4)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013633

RESUMEN

INTRODUCTION: Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR. RESEARCH DESIGN AND METHODS: We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects. RESULTS: Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein (Mgarp) gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells. CONCLUSIONS: This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.


Asunto(s)
Retinopatía Diabética , Células Endoteliales , Perfilación de la Expresión Génica , Análisis de la Célula Individual , Retinopatía Diabética/genética , Retinopatía Diabética/patología , Células Endoteliales/patología , Células Endoteliales/metabolismo , Humanos , Animales , Proliferación Celular , Retina/patología , Retina/metabolismo , Transcriptoma , Movimiento Celular/genética , Ratones , Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización Patológica/genética , Proteínas Mitocondriales/genética , Células Cultivadas
5.
BMC Med Genomics ; 17(1): 164, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898455

RESUMEN

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.


Asunto(s)
Biología Computacional , Mieloma Múltiple , Ubiquitinación , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Biología Computacional/métodos , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Nomogramas , Análisis por Conglomerados
6.
BMC Med ; 22(1): 229, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38853264

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear. METHODS: Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression. RESULTS: RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway. CONCLUSIONS: Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.


Asunto(s)
Síndrome del Ovario Poliquístico , Edición de ARN , eIF-2 Quinasa , Humanos , Síndrome del Ovario Poliquístico/genética , Femenino , Edición de ARN/genética , eIF-2 Quinasa/genética , Adulto , Células HEK293 , Perfilación de la Expresión Génica , Relevancia Clínica
7.
Mol Cancer ; 23(1): 132, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926757

RESUMEN

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Carcinoma de Células Renales , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Proteínas de Fusión Oncogénica , Humanos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Proteínas de Fusión Oncogénica/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Reordenamiento Génico , Biomarcadores de Tumor/genética , Resultado del Tratamiento , Pronóstico , Péptidos y Proteínas de Señalización Intracelular/genética
8.
PLoS One ; 19(6): e0303948, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843204

RESUMEN

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.


Asunto(s)
Terapia por Acupuntura , Periodo Posparto , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Terapia por Acupuntura/métodos , Terapia por Acupuntura/efectos adversos , Femenino , Lactancia , Prolactina/sangre , Lactancia Materna , Resultado del Tratamiento , Galactorrea/terapia , Leche Humana
10.
Comput Biol Med ; 177: 108610, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38820776

RESUMEN

Accurately quantifying the height of central serous chorioretinopathy (CSCR) lesion is of great significance for assisting ophthalmologists in diagnosing CSCR and evaluating treatment efficacy. The manual measurement results dominated by single optical coherence tomography (OCT) B-scan image in clinical practice face the dilemma of weak reference, poor reproducibility, and experience dependence. In this context, this paper constructs two schemes: Scheme Ⅰ draws on the idea of ensemble learning, namely, integrating multiple models for locating starting key point in the height direction of lesion in the inference stage, which appropriately improves the performance of a single model. Scheme Ⅱ designs an adaptive gradient threshold (AGT) technique, followed by the construction of cascading strategy, which involves preliminary location of starting key point through deep learning, and then employs AGT for precise adjustment. This strategy not only achieves effective location for starting key point, but also significantly reduces the large appetite of deep learning model for training samples. Subsequently, AGT continues to play a crucial role in locating the terminal key point in the height direction of lesion, further demonstrating its feasibility and effectiveness. Quantitative and qualitative key point location experiments in the height direction of lesion on 1152 samples, as well as the final height measurement display, consistently conveys the superiority of the constructed schemes, especially the cascading strategy, expanding another potential tool for the comprehensive analysis of CSCR.


Asunto(s)
Coriorretinopatía Serosa Central , Aprendizaje Profundo , Tomografía de Coherencia Óptica , Humanos , Coriorretinopatía Serosa Central/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Interpretación de Imagen Asistida por Computador/métodos , Algoritmos
11.
BMC Genomics ; 25(1): 431, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693480

RESUMEN

Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.


Asunto(s)
COVID-19 , Edición de ARN , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/virología , SARS-CoV-2/genética , Adenosina/metabolismo , Inosina/metabolismo , Inosina/genética , Transcriptoma , Ojo/metabolismo , Ojo/virología
12.
Biochem Biophys Res Commun ; 720: 150065, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38749188

RESUMEN

Neovascular eye diseases, including proliferative diabetic retinopathy and retinopathy of prematurity, is a major cause of blindness. Laser ablation and intravitreal anti-VEGF injection have shown their limitations in treatment of retinal neovascularization. Identification of a new therapeutic strategies is in urgent need. Our study aims to assess the effects of Cryptotanshinone (CPT), a natural compound derived from Salvia miltiorrhiza Bunge, in retina neovascularization and explore its potential mechanism. Our study demonstrated that CPT did not cause retina tissue toxicity at the tested concentrations. Intravitreal injections of CPT reduced pathological angiogenesis and promoted physical angiogenesis in oxygen-induced retinopathy (OIR) model. CPT improve visual function in OIR mice and reduced cell apoptosis. Moreover, we also revealed that CPT diminishes the expression of inflammatory cytokines in the OIR retina. In vitro, the administration of CPT effectively inhibited endothelial cells proliferation, migration, sprouting, and tube formation induced by the stimulation of human retinal vascular endothelial cells (HRVECs) with VEGF165. Mechanistically, CPT blocking the phosphorylation of VEGFR2 and downstream targeting pathway. After all, the findings demonstrated that CPT exhibits potent anti-angiogenic and anti-inflammatory effects in OIR mice, and it has therapeutic potential for the treatment of neovascular retinal diseases.


Asunto(s)
Inyecciones Intravítreas , Ratones Endogámicos C57BL , Fenantrenos , Neovascularización Retiniana , Animales , Fenantrenos/farmacología , Fenantrenos/administración & dosificación , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/patología , Neovascularización Retiniana/metabolismo , Humanos , Ratones , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/administración & dosificación , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología
13.
BMJ Open ; 14(4): e077623, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38569691

RESUMEN

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).

15.
Cell Death Discov ; 10(1): 196, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38670942

RESUMEN

Uveal melanoma (UVM), an uncommon yet potentially life-threatening ocular cancer, arises from melanocytes in the uveal tract of the eye. The exploration of novel oncotargets for UVM is of paramount importance. In this study, we show that PCK1 (phosphoenolpyruvate carboxykinase 1) expression is upregulated in various UVM tissues as well as in primary UVM cells and immortalized lines. Furthermore, bioinformatics studies reveal that PCK1 overexpression in UVM correlates with advanced disease stages and poor patient survival. Genetic silencing (utilizing viral shRNA) or knockout (via CRISPR/Cas9) of PCK1 significantly curtailed cell viability, proliferation, cell cycle progression, and motility, while provoking apoptosis in primary and immortalized UVM cells. Conversely, ectopic overexpression of PCK1, achieved through a viral construct, bolstered UVM cell proliferation and migration. Gαi3 expression and Akt phosphorylation were reduced following PCK1 silencing or knockout, but increased after PCK1 overexpression in UVM cells. Restoring Akt phosphorylation through a constitutively active mutant Akt1 (S473D) ameliorated the growth inhibition, migration suppression, and apoptosis induced by PCK1 silencing in UVM cells. Additionally, ectopic expression of Gαi3 restored Akt activation and counteracted the anti-UVM cell effects by PCK1 silencing. In vivo, the growth of subcutaneous xenografts of primary human UVM cells was significantly inhibited following intratumoral injection of adeno-associated virus (aav) expressing PCK1 shRNA. PCK1 depletion, Gαi3 downregulation, Akt inhibition, proliferation arrest, and apoptosis were detected in PCK1-silenced UVM xenografts. Collectively, our findings demonstrate that PCK1 promotes UVM cell growth possibly by modulating the Gαi3-Akt signaling pathway.

16.
Front Immunol ; 15: 1379853, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650937

RESUMEN

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.


Asunto(s)
Fenotipo , Animales , Ratones , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos/inmunología , Proliferación Celular , Línea Celular Tumoral , Ratones Endogámicos C57BL , Apoptosis , Fagocitosis , Movimiento Celular/inmunología
17.
Sci Adv ; 10(16): eadn2752, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38630828

RESUMEN

Nonlocal effects originating from interactions between neighboring meta-atoms introduce additional degrees of freedom for peculiar characteristics of metadevices, such as enhancement, selectivity, and spatial modulation. However, they are generally difficult to manipulate because of the collective responses of multiple meta-atoms. Here, we experimentally demonstrate the nonlocal metasurface to realize the spatial modulation of dark-field emission. Plasmonic asymmetric split rings (ASRs) are designed to simultaneously excite local dipole resonance and nonlocal quasi-bound states in the continuum and spatially extended modes. With one type of unit, nonlocal effects are tailored by varying array periods. ASRs at the metasurface's edge lack sufficient interactions, resulting in stronger dark-field scattering and thus edge emission properties of the metasurface. Pixel-level spatial control is demonstrated by simply erasing some units, providing more flexibility than conventional local metasurfaces. This work paves the way for manipulating nonlocal effects and facilitates applications in optical trapping and sorting at the nanoscale.

18.
Front Neurosci ; 18: 1337739, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38586196

RESUMEN

Background: Anxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians. Methods: We searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords. Results: A total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively. Conclusion: The study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind-body exercise to improve mood. In addition, future researchers can explore the mind-body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.

19.
Heliyon ; 10(8): e29334, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655307

RESUMEN

Purpose: To develop a multimodal deep transfer learning (DTL) fusion model using optical coherence tomography angiography (OCTA) images to predict the recurrence of retinal vein occlusion (RVO) and macular edema (ME) after three consecutive anti-VEGF therapies. Methods: This retrospective cross-sectional study consisted of 2800 B-scan OCTA macular images collected from 140 patients with RVO-ME. The central macular thickness (CMT) > 250 µm was used as a criterion for recurrence in the three-month follow-up after three injections of anti-VEGF therapy. The qualified OCTA image preprocessing and the lesion area segmentation were performed by senior ophthalmologists. We developed and validated the clinical, DTL, and multimodal fusion models based on clinical and extracted OCTA imaging features. The performance of the models and experts predictions were evaluated using several performance metrics, including the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: The DTL models exhibited higher prediction efficacy than the clinical models and experts' predictions. Among the DTL models, the Vgg19 performed better than that of the other models, with an AUC of 0.968 (95 % CI, 0.943-0.994), accuracy of 0.913, sensitivity of 0.922, and specificity of 0.902 in the validation cohort. Moreover, the fusion Vgg19 model showed the highest prediction efficacy among all the models, with an AUC of 0.972 (95 % CI, 0.946-0.997), accuracy of 0.935, sensitivity of 0.935, and specificity of 0.934 in the validation cohort. Conclusions: Multimodal fusion DTL models showed robust performance in predicting RVO-ME recurrence and may be applied to assist clinicians in determining patients' follow-up time after anti-VEGF therapy.

20.
Polymers (Basel) ; 16(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38543333

RESUMEN

In order to solve the problems of insufficient active functions (antibacterial and antioxidant activities) and the poor degradability of traditional plastic packaging materials, biodegradable chitosan (CS)/polyvinyl alcohol (PVA) nanocomposite active films reinforced with natural plant polyphenol-quercetin functionalized layered clay nanosheets (QUE-LDHs) were prepared by a solution casting method. In this study, QUE-LDHs realizes a combination of the active functions of QUE and the enhancement effect of LDHs nanosheets through the deposition and complexation of QUE and copper ions on the LDHs. Infrared and thermal analysis results revealed that there was a strong interface interaction between QUE-LDHs and CS/PVA matrix, resulting in the limited movement of PVA molecules and the increase in glass transition temperature and melting temperature. With the addition of QUE-LDHs, the active films showed excellent UV barrier, antibacterial, antioxidant properties and tensile strength, and still had certain transparency in the range of visible light. As QUE-LDHs content was 3 wt%, the active films exhibited a maximum tensile strength of 58.9 MPa, representing a significant increase of 40.9% compared with CS/PVA matrix. Notably, the UV barrier (280 nm), antibacterial (E. coli) and antioxidant activities (DPPH method) of the active films achieved 100.0%, 95.5% and 58.9%, respectively. Therefore, CS/PVA matrix reinforced with QUE-LDHs has good potential to act as an environmentally and friendly active packaging film or coating.

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