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1.
BMC Biol ; 22(1): 80, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609974

RESUMO

BACKGROUND: The nuclear lamina links the nuclear membrane to chromosomes and plays a crucial role in regulating chromatin states and gene expression. However, current knowledge of nuclear lamina in plants is limited compared to animals and humans. RESULTS: This study mainly focused on elucidating the mechanism through which the putative nuclear lamina component protein KAKU4 regulates chromatin states and gene expression in Arabidopsis leaves. Thus, we constructed a network using the association proteins of lamin-like proteins, revealing that KAKU4 is strongly associated with chromatin or epigenetic modifiers. Then, we conducted ChIP-seq technology to generate global epigenomic profiles of H3K4me3, H3K27me3, and H3K9me2 in Arabidopsis leaves for mutant (kaku4-2) and wild-type (WT) plants alongside RNA-seq method to generate gene expression profiles. The comprehensive chromatin state-based analyses indicate that the knockdown of KAKU4 has the strongest effect on H3K27me3, followed by H3K9me2, and the least impact on H3K4me3, leading to significant changes in chromatin states in the Arabidopsis genome. We discovered that the knockdown of the KAKU4 gene caused a transition between two types of repressive epigenetics marks, H3K9me2 and H3K27me3, in some specific PLAD regions. The combination analyses of epigenomic and transcriptomic data between the kaku4-2 mutant and WT suggested that KAKU4 may regulate key biological processes, such as programmed cell death and hormone signaling pathways, by affecting H3K27me3 modification in Arabidopsis leaves. CONCLUSIONS: In summary, our results indicated that KAKU4 is directly and/or indirectly associated with chromatin/epigenetic modifiers and demonstrated the essential roles of KAKU4 in regulating chromatin states, transcriptional regulation, and diverse biological processes in Arabidopsis.


Assuntos
Arabidopsis , Cromatina , Animais , Humanos , Cromatina/genética , Histonas , Arabidopsis/genética , Lâmina Nuclear , Regulação da Expressão Gênica , Proteínas Nucleares
2.
Am J Physiol Cell Physiol ; 326(5): C1367-C1383, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38406826

RESUMO

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.


Assuntos
Modelos Animais de Doenças , Ferro , Degeneração Macular , Epitélio Pigmentado da Retina , Animais , Humanos , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/genética , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Camundongos , Ferro/metabolismo , Camundongos Endogâmicos C57BL , Apoptose , Estresse Oxidativo , Linhagem Celular , Senescência Celular , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Proliferação de Células , Retina/metabolismo , Retina/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia
3.
BMC Plant Biol ; 24(1): 177, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38448830

RESUMO

Lamins are the major components of the nuclear lamina, which regulate chromatin structure and gene expression. KAKU4 is a unique nuclear lamina component in the nuclear periphery, modulates nuclear shape and size in Arabidopsis. The knowledge about the regulatory role of KAKU4 in leaf development remains limited. Here we found that knockdown of KAKU4 resulted in an accelerated leaf senescence phenotype, with elevated levels of H2O2 and hormones, particularly SA, JA, and ABA. Our results demonstrated the importance of KAKU4 as a potential negative regulator in age-triggered leaf senescence in Arabidopsis. Furthermore, we conducted combination analyses of transcriptomic and epigenomic data for the kaku4 mutant and WT leaves. The knockdown of KAKU4 lowered H3K27me3 deposition in the up-regulated genes associated with hormone pathways, programmed cell death, and leaf senescence, including SARD1, SAG113/HAI1, PR2, and so forth. In addition, we found the functional crosstalks between KAKU4 and its associated proteins (CRWN1/4, PNET2, GBPL3, etc.) through comparing multiple transcriptome datasets. Overall, our results indicated that KAKU4 may inhibit the expression of a series of genes related to hormone signals and H2O2 metabolism by affecting the deposition of H3K27me3, thereby suppressing leaf senescence.


Assuntos
Arabidopsis , Arabidopsis/genética , Histonas , Peróxido de Hidrogênio , Senescência Vegetal , Hormônios
4.
Nutr Cancer ; 76(6): 529-542, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567899

RESUMO

Astaxanthin (AST) is a natural marine carotenoid with a variety of biological activities. This study aimed to demonstrate the possible mechanisms by which AST improves skeletal muscle atrophy in cancer cachexia. In this study, the effects of different doses of AST (30 mg/kg b.w., 60 mg/kg b.w. and 120 mg/kg b.w.) on skeletal muscle functions were explored in mice with cancer cachexia. The results showed that AST (30, 60 and 120 mg/kg b.w.) could effectively protect cachexia mice from body weight and skeletal muscle loss. AST dose-dependently ameliorated the decrease in myofibres cross-sectional area and increased the expression of myosin heavy chain (MHC). AST treatment decreased both the serum and muscle level of IL-6 but not TNF-α in C26 tumor-bearing cachexia mice. Moreover, AST alleviated skeletal muscle atrophy by decreasing the expression of two muscle-specific E3 ligases MAFBx and MuRF-1. AST improved mitochondrial function by downregulating the levels of muscle Fis1, LC3B and Bax, upregulating the levels of muscle Mfn2 and Bcl-2. In conclusion, our study show that AST might be expected to be a nutritional supplement for cancer cachexia patients.


Assuntos
Caquexia , Músculo Esquelético , Atrofia Muscular , Xantofilas , Animais , Xantofilas/farmacologia , Caquexia/tratamento farmacológico , Caquexia/etiologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Camundongos , Masculino , Proteínas Musculares/metabolismo , Interleucina-6/metabolismo , Camundongos Endogâmicos BALB C , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Cadeias Pesadas de Miosina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Linhagem Celular Tumoral
5.
Fish Shellfish Immunol ; 144: 109283, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092094

RESUMO

L-type lectins (LTLs) contain a carbohydrate recognition domain homologous to leguminous lectins, and have functions in selective protein trafficking, sorting and targeting in the secretory pathway of animals. In this study, a novel LTL, designated as ToERGIC-53, was cloned and identified from obscure puffer Takifugu obscurus. The open reading frame of ToERGIC-53 contained 1554 nucleotides encoding 517 amino acid residues. The deduced ToERGIC-53 protein consisted of a signal peptide, a leguminous lectin domain (LTLD), a coiled-coil region, and a transmembrane region. Quantitative real-time PCR showed that ToERGIC-53 was expressed in all examined tissues, with the highest expression level in the liver. The expression of ToERGIC-53 was significantly upregulated after infection with Vibrio harveyi and Staphylococcus aureus. Recombinant ToERGIC-53-LTLD (rToERGIC-53-LTLD) protein could not only agglutinate and bind to one Gram-positive bacterium (S. aureus) and three Gram-negative bacteria (V. harveyi, V. parahaemolyticus and Aeromonas hydrophila), but also bind to glycoconjugates on the surface of bacteria such as lipopolysaccharide, peptidoglycan, mannose and galactose. In addition, rToERGIC-53-LTLD inhibited the growth of bacteria in vitro. All these results suggested that ToERGIC-53 might be a pattern recognition receptor involved in antibacterial immune response of T. obscurus.


Assuntos
Infecções Bacterianas , Lectinas , Animais , Lectinas/genética , Takifugu/genética , Takifugu/metabolismo , Staphylococcus aureus/metabolismo , Receptores de Reconhecimento de Padrão/genética , Filogenia , Imunidade Inata/genética , Lectinas Tipo C/genética
6.
Nucleic Acids Res ; 50(D1): D1456-D1467, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34534340

RESUMO

With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.


Assuntos
Bases de Dados Genéticas , Anotação de Sequência Molecular , Plantas/classificação , Software , Cromatina/genética , Plantas/genética
7.
J Dairy Sci ; 107(6): 3400-3412, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38135045

RESUMO

Hypothyroidism has been found to have an effect on the nutritional composition of human milk during pregnancy. This study aims to explore the combined influence of rheological properties, macronutrient content, particle size, and the zeta potential of milk fat globules, as well as the composition of milk fat globule membrane (MFGM) proteins on the quality of human milk in gestational hypothyroidism. The study revealed that human milk from the group with hypothyroidism during pregnancy (AHM) was less viscoelastic and stable when compared with normal pregnancy group human milk (NHM). Furthermore, the particle size and macronutrient content of NHM were found to be larger than that of AHM. In contrast, the zeta potential of AHM was greater than that of NHM. The sodium dodecyl sulfate-PAGE results disclosed that the composition of MFGM proteins in these 2 groups were generally the same, but the content of AHM was lower than that of NHM. In conclusion, this study confirms that hypothyroidism during pregnancy can have a significant effect on the quality of human milk.


Assuntos
Hipotireoidismo , Leite Humano , Reologia , Feminino , Humanos , Gravidez , Leite Humano/química , Hipotireoidismo/veterinária , Glicolipídeos
8.
Artigo em Inglês | MEDLINE | ID: mdl-38231603

RESUMO

PURPOSE: To evaluate the outcomes of modified combined fascia sheath and levator muscle complex suspension to correct severe congenital ptosis in pediatrics and the effect on refractive status. METHODS: This prospective, case series study enrolled patients (aged ≤18 years) with simple severe congenital ptosis at Zhongshan Ophthalmic Center. All patients were treated with combined fascia sheath + levator muscle suspension and followed up for 3 months. Preoperative and postoperative cycloplegic refraction and the best-corrected visual acuity were performed. The types of astigmatism include with-the-rule, against-the-rule, and oblique. RESULTS: Thirty-six patients (50 eyes) were enrolled. The mean age was 7.11 ± 3.72 years. The surgery success rate was 90.0%. Following surgery, the eyelid contour of all eyes exhibited natural symmetry and satisfactory curvature. The eyelid height difference in OUs was ≤1 mm for 42 eyes. For 47 eyes, the eyelid crease was symmetry. Two eyes had conjunctival prolapse, and 1 eye developed trichiasis. After surgery, cylinder power changed from mean -1.14 ± 1.27 D to -1.54 ± 1.25 D (p < 0.001) and best-corrected visual acuity improved from mean 0.205 ± 0.217 logarithm of the minimum angle of resolution to 0.168 ± 0.176 logarithm of the minimum angle of resolution (p = 0.048). The quantities of with-the-rule increased from 35 eyes to 41 eyes, oblique from 4 eyes to 6 eyes, while against-the-rule decreased from 11 eyes to 3 eyes (p = 0.01). CONCLUSIONS: Combined fascia sheath + levator muscle suspension under general anesthesia is effective and safe for severe congenital ptosis in pediatrics. However, astigmatism increased and the types of astigmatism changed after surgery.

9.
Molecules ; 29(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38542979

RESUMO

Recently, perovskite (ABO3) nanomaterials have been widely explored as a class of versatile electrocatalysts for oxygen evolution reactions (OER) due to their remarkable compositional flexibility and structural tunability, but their poor electrical conductivity hinders hydrogen evolution reaction (HER) activity and further limits the large-scale application of perovskite oxide in overall water splitting (OWS). In this study, hollow-nanotube-structure LaxCo0.4Fe0.6O3-δ (x = 1.0, 0.9, and 0.8) perovskites with superior HER/OER activity were synthesized on nickel-iron alloy foam (denoted LaxCoFe/NFF) using hydrothermal with a subsequent calcination strategy. Among them, La0.9CoFe/NFF not only exhibited extraordinary HER electrocatalytic performance (160.5 mV@10 mA cm-2 and 241.0 mV@100 mA cm-2) and stability (20 h@10 mA cm-2), but also displayed significant OER electrocatalytic activity (234.7 mV@10 mA cm-2 and 296.1 mV@100 mA cm-2) and durability (20 h@10 mA cm-2), outperforming many recently reported HER/OER perovskite catalysts. The increase in oxygen vacancies caused by the introduction of La deficiency leads to the expansion of the lattice, which greatly accelerates the HER/OER process of La0.9CoFe/NFF. Additionally, the naturally porous skeleton can prevent catalysts from aggregating as well as delay the corrosion and dissolution of catalysts in the electrolyte under high applied potentials. Furthermore, the assembled two-electrode configuration, utilizing La0.9CoFe/NFF (cathode and anode) electrodes, only requires a low cell voltage of 1.573 V at 10 mA cm-2 for robust alkaline OWS, accompanied by remarkable durability over 20 h. This work provides inspiration for the design and preparation of high-performance and stable bifunctional perovskite electrocatalysts for OWS.

10.
Int Ophthalmol ; 44(1): 277, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916702

RESUMO

PURPOSE: Exploring the prevalence of dry eye (DE) and the changes of tear film stability in patients with primary acquired obstruction of the nasolacrimal duct (PANDO). METHODS: In this cross-sectional, observational study, 370 eyes in 223 patients with PANDO were assessed. The ocular surface disease index (OSDI) was used to evaluate ocular surface symptoms, and the Keratograph 5M non-invasive ocular surface analyser was used to assess ocular surface parameters. According to the TFOS DEWS II criteria, patients with OSDI ≥ 13 and NIKBUT < 10 s were diagnosed with DE. RESULTS: Of the 223 PANDO patients, 65 (29.1%) met the diagnostic criteria for DE. Compared with patients without DE, PANDO patients with DE were significantly older (p < 0.001), had a longer duration of epiphora (p = 0.023), and more likely to have a positive regurgitation on pressure over the lacrimal sac (ROPLAS) sign (p = 0.003). Multifactorial analysis showed that older age, positive ROPLAS and hypertension were significant independent predictors of DE (p < 0.05). Among the 147 unilateral PANDO patients without DE, the TMH, NIKBUT-first, NIKBUT-average and bulbar erythema scores were significantly higher in the PANDO sides. CONCLUSIONS: This study illustrated the prevalence of DE in PANDO patients was 29.1% and DE is more likely to occur in those who are older, have hypertension and are positive for ROPLAS. In addition, in patients with unilateral nasolacrimal duct obstruction, a decrease in tear film stability was observed in the healthy eye.


Assuntos
Síndromes do Olho Seco , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Lágrimas , Humanos , Obstrução dos Ductos Lacrimais/diagnóstico , Feminino , Masculino , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/metabolismo , Estudos Transversais , Lágrimas/metabolismo , Lágrimas/fisiologia , Pessoa de Meia-Idade , Idoso , Prevalência , Adulto , Idoso de 80 Anos ou mais
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 174-180, 2024 Feb 15.
Artigo em Zh | MEDLINE | ID: mdl-38436316

RESUMO

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.


Assuntos
Comportamento Problema , Pré-Escolar , Humanos , Função Executiva , Percepção Auditiva , China , Pais
12.
Plant J ; 110(3): 863-880, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35167131

RESUMO

Plant Knotted1-like homeobox (KNOX) genes encode homeodomain-containing transcription factors. In rice (Oryza sativa L.), little is known about the downstream target genes of KNOX Class II subfamily proteins. Here we generated chromatin immunoprecipitation (ChIP)-sequencing datasets for HOS59, a member of the rice KNOX Class II subfamily, and characterized the genome-wide binding sites of HOS59. We conducted trait ontology (TO) analysis of 9705 identified downstream target genes, and found that multiple TO terms are related to plant structure morphology and stress traits. ChIP-quantitative PCR (qPCR) was conducted to validate some key target genes. Meanwhile, our IP-MS datasets showed that HOS59 was closely associated with BELL family proteins, some grain size regulators (OsSPL13, OsSPL16, OsSPL18, SLG, etc.), and some epigenetic modification factors such as OsAGO4α and OsAGO4ß, proteins involved in small interfering RNA-mediated gene silencing. Furthermore, we employed CRISPR/Cas9 editing and transgenic approaches to generate hos59 mutants and overexpression lines, respectively. Compared with wild-type plants, the hos59 mutants have longer grains and increased glume cell length, a loose plant architecture, and drooping leaves, while the overexpression lines showed smaller grain size, erect leaves, and lower plant height. The qRT-PCR results showed that mutation of the HOS59 gene led to upregulation of some grain size-related genes such as OsSPL13, OsSPL18, and PGL2. In summary, our results indicate that HOS59 may be a repressor of the downstream target genes, negatively regulating glume cell length, rice grain size, plant architecture, etc. The identified downstream target genes and possible interaction proteins of HOS59 improve our understanding of the KNOX regulatory networks.


Assuntos
Oryza , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Oryza/genética , Oryza/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Cancer Cell Int ; 23(1): 12, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707875

RESUMO

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

14.
Exp Eye Res ; 234: 109572, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451566

RESUMO

Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1ß, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Leucostasia , Camundongos , Humanos , Animais , Retinopatia Diabética/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fator VIII/metabolismo , Fator VIII/farmacologia , Fator VIII/uso terapêutico , Células Endoteliais/metabolismo , Leucostasia/metabolismo , Retina/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo
15.
Exp Eye Res ; 233: 109524, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37290629

RESUMO

Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) is a potential regulator of photoreceptor development. To investigate the mechanisms underlying MAP4K4 during the neuronal development of retinal photoreceptors, we generated knockout models of C57BL/6j mice in vivo and 661 W cells in vitro. Our findings revealed homozygous lethality and neural tube malformation in mice subjected to Map4k4 DNA ablation, providing evidence for the involvement of MAP4K4 in early stage embryonic neural formation. Furthermore, our study demonstrated that the ablation of Map4k4 DNA led to the vulnerability of photoreceptor neurites during induced neuronal development. By monitoring transcriptional and protein variations in mitogen-activated protein kinase (MAPK) signaling pathway-related factors, we discovered an imbalance in neurogenesis-related factors in Map4k4 -/- cells. Specifically, MAP4K4 promotes jun proto-oncogene (c-JUN) phosphorylation and recruits other factors related to nerve growth, ultimately leading to the robust formation of photoreceptor neurites. These data suggest that MAP4K4 plays a decisive role in regulating the fate of retinal photoreceptors through molecular modulation and contributes to our understanding of vision formation.


Assuntos
Neurogênese , Transdução de Sinais , Animais , Camundongos , DNA , Camundongos Endogâmicos C57BL , Células Fotorreceptoras de Vertebrados , Quinase Induzida por NF-kappaB
16.
Amino Acids ; 55(3): 325-336, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36604337

RESUMO

Doxorubicin (DOX) is a cornerstone of chemotherapy for solid tumors and leukemias. DOX-induced cognitive impairment, termed chemo brain, has been reported in cancer survivors, whereas its mechanism remains poorly understood. Here we initially evaluated the cognitive impairments of mice treated with clinically relevant, long-term, low-dosage of DOX. Using HILIC-MS/MS-based targeted metabolomics, we presented the changes of 21 amino acids across six anatomical brain regions of mice with DOX-induced chemo brain. By mapping the altered amino acids to the human metabolic network, we constructed an amino acid-based network module for each brain region. We identified phenylalanine, tyrosine, methionine, and γ-aminobutyric acid as putative signatures of three regions (hippocampus, prefrontal cortex, and neocortex) highly associated with cognition. Relying on the reported mouse brain metabolome atlas, we found that DOX might perturb the amino acid homeostasis in multiple brain regions, similar to the changes in the aging brain. Correlation analysis suggested the possible indirect neurotoxicity of DOX that altered the brain levels of phenylalanine, tyrosine, and methionine by causing metabolic disorders in the liver and kidney. In summary, we revealed the region-specific amino acid signatures as actionable targets for DOX-induced chemo brain, which might provide safer treatment and improve the quality of life among cancer survivors.


Assuntos
Qualidade de Vida , Espectrometria de Massas em Tandem , Camundongos , Humanos , Animais , Doxorrubicina/efeitos adversos , Encéfalo/metabolismo , Aminoácidos/metabolismo , Metionina/metabolismo , Tirosina/metabolismo , Fenilalanina/metabolismo
17.
Lasers Med Sci ; 38(1): 75, 2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36807698

RESUMO

The objective of this study was to evaluate the efficacy and safety of super pulse CO2 laser-assisted punctoplasty with canalicular curettage in primary canaliculitis. In this retrospective serial case study, the clinical data of 26 patients who underwent super pulse CO2 laser-assisted punctoplasty for the treatment of canaliculitis were collected from January 2020 to May 2022. The clinical presentation, intraoperative and microbiologic findings, surgical pain severity, postoperative outcome, and complications were studied. Of the 26 patients, most were females (female:male 20:6), with a mean age of 60.1 ± 16.1 years (range, 19-93). Mucopurulent discharge (96.2%), eyelid redness and swelling (53.8%), and epiphora (38.5%) were the most common presentations. During the surgery, concretions were present in 73.1% (19/26) of the patients. The surgical pain severity scores ranged from 1 to 5, according to the visual analog scale, with a mean score of 3.2 ± 0.8. This procedure resulted in complete resolution in 22 (84.6%) patients and significant improvement in 2 (7.7%) patients, and 2 (7.7%) patients required additional lacrimal surgery with a mean follow-up time of 10.9 ± 3.7 months. The surgical procedure of super pulse CO2 laser-assisted punctoplasty followed by curettage appears to be a safe, effective, minimally invasive, and well-tolerated treatment for primary canaliculitis.


Assuntos
Canaliculite , Lasers de Gás , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Canaliculite/tratamento farmacológico , Canaliculite/cirurgia , Estudos Retrospectivos , Dióxido de Carbono/uso terapêutico , Curetagem/métodos , Resultado do Tratamento
18.
Sensors (Basel) ; 23(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37050834

RESUMO

With the rapid development of Internet of Things technology, cloud computing, and big data, the combination of medical systems and information technology has become increasingly close. However, the emergence of intelligent medical systems has brought a series of network security threats and hidden dangers, including data leakage and remote attacks, which can directly threaten patients' lives. To ensure the security of medical information systems and expand the application of zero trust in the medical field, we combined the medical system with the zero-trust security system to propose a zero-trust medical security system. In addition, in its dynamic access control module, based on the RBAC model and the calculation of user behavior risk value and trust, an access control model based on subject behavior evaluation under zero-trust conditions (ABEAC) was designed to improve the security of medical equipment and data. Finally, the feasibility of the system is verified through a simulation experiment.


Assuntos
Segurança Computacional , Confiança , Humanos , Big Data , Simulação por Computador , Computação em Nuvem
19.
Int Ophthalmol ; 43(1): 63-71, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35838862

RESUMO

PURPOSE: This study evaluated the long-term outcomes of endoscopic suturing and knotting-dacryocystorhinostomy (eSK-DCR) without the use of a stent or mitomycin C. METHODS: A prospective interventional case series was performed on patients with nasolacrimal duct obstruction (NLDO) who underwent eSK-DCR at Zhongshan Ophthalmic Center from October 2019 to December 2019. The surgeon sutured the lacrimal sac mucosa with the nasal mucosa by tying knots under endoscopic DCR. Subject demographics, preoperative data and postoperative data were collected, including clinical presentation, Munk score for epiphora, surgical indications, operation time, duration of knotting, number of knots, endoscopic ostium size, complications, and anatomical and functional success. Anatomic success was defined as patent ostium on lacrimal irrigation, and functional success was defined as subjective improvement in symptoms. Statistical analysis was performed by IBM SPSS software (Version 20.0; SPSS Inc., Chicago, IL, USA). RESULTS: A total of 60 patients (71 eyes) underwent pure eSK-DCR. Of these, 95.0% (57/60) were females. The mean age of the patients was 54.7 years. The mean surgical time was 37.60 min, and the average time for each knotting was 2.86 min. Endoscopic evidence found that all patients showed patent ostium and normal healing of the flaps after 4 weeks. The Munk scores dropped significantly at 6 months postoperatively compared to preoperative scores (P < 0.0001). Although 4 patients (7 eyes) were lost to follow-up at the end of the 2-year period, the anatomical and functional success remained stable during the 2-year follow-up period (anatomical, 100%; functional, 87.5%). No serious complications were detected during the follow-up period. CONCLUSION: Pure eSK-DCR is a simple and reliable therapeutic method for the management of NLDO. The surgical outcomes were good and remained stable beyond 6 months postoperatively.


Assuntos
Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Dacriocistorinostomia/efeitos adversos , Dacriocistorinostomia/métodos , Obstrução dos Ductos Lacrimais/terapia , Obstrução dos Ductos Lacrimais/etiologia , Ducto Nasolacrimal/cirurgia , Estudos Prospectivos , Mitomicina/uso terapêutico , Endoscopia/métodos , Resultado do Tratamento , Estudos Retrospectivos
20.
Int Ophthalmol ; 43(9): 3363-3371, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37338773

RESUMO

BACKGROUND: The aim was to clarify the distributions of bacteria in the conjunctival sac and lacrimal sac in patients with chronic dacryocystitis. METHODS: In total, 297 (322 eyes) chronic dacryocystitis patients who underwent nasal endoscopic dacryocystorhinostomy (EN-DCR) were included. Conjunctival sac secretions from the affected eye were collected preoperatively, and lacrimal sac retention fluid from the affected side in the same patient was collected intraoperatively. Bacterial culture and drug sensitivity testing were performed to determine bacterial distributions. RESULTS: In total, 127 bacterial isolates (49 species) were detected in 123 eyes in the conjunctival group, with a positivity rate of 38.2% (123/322); 85 bacterial isolates (30 species) were detected in 85 eyes in the lacrimal sac group, with a positivity rate of 26.4% (85/322). The positivity rates were significantly different (P = 0.001) between two groups. The gram-negative bacilli proportion in the lacrimal sac group (36/85, 42.4%) was significantly higher than that in the conjunctival sac group (37/127, 29.2%) ( P = 0.047). Positive conjunctival sac secretion culture (123/322) was significantly associated with increased ocular secretion (281/322, 87.3%) (P = 0.002). Among the culture-positive bacteria in the conjunctival sac group and the lacrimal sac group, 30/127, 23.6% and 43/127, 26.7% and 21/85, 24.7% and 20/85, 23.5% were resistant to levofloxacin and tobramycin, respectively. CONCLUSIONS: This study illustrated differences in bacterial distributions between conjunctival sac secretions and retained lacrimal sac fluid in chronic dacryocystitis patients, with a higher proportion of gram-negative bacilli in lacrimal sac secretions. The ocular surface flora in chronic dacryocystitis patients is partially resistant to levofloxacin and tobramycin, which need to be considered by ophthalmologists.


Assuntos
Dacriocistite , Dacriocistorinostomia , Ducto Nasolacrimal , Humanos , Ducto Nasolacrimal/cirurgia , Levofloxacino , Centros de Atenção Terciária , Dacriocistite/microbiologia , Dacriocistite/cirurgia , Bactérias , Tobramicina , Túnica Conjuntiva , Bactérias Gram-Negativas
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