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1.
Nat Plants ; 10(9): 1363-1376, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39242981

RESUMEN

Over the past three decades, researchers have isolated plant mutants that show constitutively activated defence responses in the absence of pathogen infection. These mutants are called autoimmune mutants and are typically dwarf and/or bearing chlorotic/necrotic lesions. Here, from a genetic screen for Arabidopsis genes involved in maintaining a normal leaf microbiota, we identified TIP GROWTH DEFECTIVE 1 (TIP1), which encodes an S-acyltransferase, as a key player in guarding leaves against abnormal microbiota level and composition under high-humidity conditions. The tip1 mutant has several characteristic phenotypes of classical autoimmune mutants, including a dwarf stature, showing lesions, and having a high basal level of defence gene expression. Gnotobiotic experiments revealed that the autoimmune phenotypes of the tip1 mutant are largely dependent on the presence of microbiota as axenic tip1 plants have markedly reduced autoimmune phenotypes. We found that the microbiota dependency of autoimmune phenotypes is shared by several 'lesion mimic'-type autoimmune mutants in Arabidopsis. It is worth noting that autoimmune phenotypes caused by mutations in two Nucleotide-Binding, Leucine-Rich Repeat (NLR) genes do not require the presence of microbiota and can even be partially alleviated by microbiota. Our results therefore suggest the existence of at least two classes of autoimmunity (microbiota-dependent versus microbiota-independent) in plants. The observed interplay between autoimmunity and microbiota in the lesion mimic class of autoimmunity is reminiscent of the interactions between autoimmunity and dysbiosis in the animal kingdom. These parallels highlight the intricate relationship between host immunity and microbial communities across various biological systems.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Autoinmunidad , Microbiota , Hojas de la Planta , Arabidopsis/microbiología , Arabidopsis/inmunología , Arabidopsis/genética , Hojas de la Planta/microbiología , Hojas de la Planta/inmunología , Hojas de la Planta/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Microbiota/inmunología , Mutación , Inmunidad de la Planta/genética , Aciltransferasas/genética , Fenotipo
2.
World J Clin Cases ; 12(26): 5885-5892, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39286370

RESUMEN

BACKGROUND: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined. AIM: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion. METHODS: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life. RESULTS: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up (P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) (P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group (P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, (P < 0.05). CONCLUSION: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39269446

RESUMEN

A Gram-stain-negative, strictly aerobic, motile, flagellated, rod-shaped, halotolerant, and poly-ß-hydroxyalkanoate-producing bacterium, designated DP4N28-3T, was isolated from offshore sediment surrounding hard coral in the Dapeng peninsula (Guangdong, PR China). Growth occurred at 15-35 °C (optimal at 30 °C), pH 6.0-9.5 (optimal at 6.0-7.0), and 0.0-30.0 % NaCl concentration (w/v, optimal at 0.0-2.0 %), showing halotolerance. Phylogeny based on 16S rRNA gene sequences, five housekeeping genes, and genome sequences identified Pseudohoeflea suaedae DSM 23348T (98.1 %, 16S rRNA gene sequence similarity) as the most related species to strain DP4N28-3T. Average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values between strain DP4N28-3T and P. suaedae DSM 23348T were all below the threshold of species demarcation. Major phenotypic differences were the flagella type and the limited sources of single carbon utilization by strain DP4N28-3T, which only included acetic acid, acetoacetic acid, d-glucuronic acid, and glucuronamide. Strain DP4N28-3T harboured the class I poly-ß-hydroxyalkanoate synthase gene (phaC) and produced poly-ß-hydroxybutyrate. The fatty acids were summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c, 49.4 %) and C16 : 0 (13.4 %). The major cellular polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, and sulfoquinovosyl diacylglycerol. The respiratory quinone was Q-10. The results of the phylogenetic, genomic, phenotypic, and chemotaxonomic analysis indicated that the isolated strain represents the type strain of a novel species. Based on these results, strain DP4N28-3T (=MCCC 1K05639T=KCTC 82803T) is proposed as the type strain of the novel species Pseudohoeflea coraliihabitans sp. nov.


Asunto(s)
Antozoos , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Hidroxibutiratos , Hibridación de Ácido Nucleico , Filogenia , Poliésteres , ARN Ribosómico 16S , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , China , Hidroxibutiratos/metabolismo , ADN Bacteriano/genética , Poliésteres/metabolismo , Sedimentos Geológicos/microbiología , Animales , Antozoos/microbiología , Polihidroxibutiratos
4.
Plants (Basel) ; 13(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39273990

RESUMEN

This study investigates the composition characteristics and anti-inflammatory activity mechanisms of the essential oil from the leaves of Crossostephium chinense. C. chinense is a perennial herb commonly found in East Asia, traditionally used to treat various ailments. The essential oil extracted through water distillation, primarily contains 1,8-cineole (13.73%), santolina triene (13.53%), and germacrene D (10.67%). Three compounds were identified from the essential oil, namely 1-acetoxy-2-(2-hydroxypropyl)-5-methylhex-3,5-diene, 1-acetoxy-isopyliden-hex-5-en-4-one, and chrysanthemyl acetate, with the first two being newly discovered compounds. Then, the essential oil of C. chinense exhibits significant anti-inflammatory effects on RAW264.7 macrophages, effectively inhibiting the production of NO and ROS, with the IC50 value of 10.3 µg/mL. Furthermore, the essential oil reduces the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß. Mechanistic studies indicate that the essential oil affects the inflammatory response by inhibiting the expression of iNOS but has no significant impact on COX-2. Further analysis suggests that the essential oil may regulate the inflammatory response through the ERK protein in the MAPK pathway and IκBα in the NF-κB pathway, while also promoting the activity of the NRF2/HO-1 antioxidant pathway, enhancing the cell's antioxidant capacity, thereby achieving an effect of inhibiting the inflammatory response. These results highlight the potential application value of C. chinense leaf essential oil in the medical and healthcare fields.

5.
Trends Microbiol ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278787

RESUMEN

The AvrE family of type III secreted effectors are highly conserved among many agriculturally important phytopathogenic bacteria. Despite their critical roles in the pathogenesis of phytopathogenic bacteria, the molecular functions and virulence mechanisms of these effectors have been largely unknown. However, recent studies have identified host-interacting proteins and demonstrated that AvrE family effectors can form water-permeable channels in the plant plasma membrane (PM) to create a hydrated and nutrient-rich extracellular space (apoplast) required for disease establishment. Here, we summarize these recent discoveries and highlight open questions related to AvrE-targeted host proteins.

6.
bioRxiv ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39091730

RESUMEN

Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.

7.
Biofactors ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143845

RESUMEN

Limonene, a dietary monocyclic monoterpene commonly found in citrus fruits and various aromatic plants, has garnered increasing interest as a gastrointestinal protectant. This study aimed to assess the effects of limonene on intestinal epithelial barrier function and investigate the involvement of cannabinoid receptor type-1 (CB1R) in vitro. Additionally, the study focused on examining the metabolomic changes induced by limonene in the intestinal epithelial cells (Caco-2). Initial analysis of transepithelial electrical resistance (TEER) revealed that both l-limonene and d-limonene, isomers of limonene, led to a dose- and time-dependent increase in TEER in normal cells and those inflamed by pro-inflammatory cytokines mixture (CytoMix). Furthermore, both types of limonene reduced CytoMix-induced paracellular permeability, as demonstrated by a decrease in Lucifer yellow flux. Moreover, d-limonene and l-limonene treatment increased the expression of tight junction molecules (TJs) such as occludin, claudin-1, and ZO-1, at both the transcriptional and translational levels. d-Limonene upregulates E-cadherin, a molecule involved in adherens junctions (AJs). Mechanistic investigations demonstrated that d-limonene and l-limonene treatment significantly inhibited CB1R at the protein, while the mRNA level remained unchanged. Notably, the inhibitory effect of d-limonene on CB1R was remarkably similar to that of pharmacological CB1R antagonists, such as rimonabant and ORG27569. d-limonene also alters Caco-2 cell metabolites. A substantial reduction in ß-glucose and 2-succinamate was detected, suggesting limonene may impact intestinal epithelial cells' glucose uptake and glutamate metabolism. These findings suggest that d-limonene's CB1R antagonistic property could effectively aid in the recovery of intestinal barrier damage, marking it a promising gastrointestinal protectant.

8.
Aesthet Surg J ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066686

RESUMEN

BACKGROUND: Rhinoplasty requires balanced consideration of function and aesthetics, necessitating a precise evaluation tool. A reliable and validated patient-reported measure, the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) evaluates both aspects but was previously unavailable in Chinese. This study fills that gap by providing a Chinese version. OBJECTIVES: This study aims to translate, culturally adapt, and validate a Chinese iteration of the SCHNOS (C-SCHNOS) for appraising the functional and aesthetic outcomes among Chinese patients post-rhinoplasty, furnishing a reliable and efficacious assessment tool for Chinese users. METHODS: Following international guidelines, the SCHNOS questionnaire was translated and culturally adapted for Chinese use. Its psychometric properties, including internal consistency, correlations, and reproducibility, were evaluated among Chinese natives in Sichuan Province from March 2022 to January 2023. RESULTS: The C-SCHNOS was administered to 110 Chinese natives, showing high internal consistency, Cronbach's α of 0.81 for SCHNOS-O (Obstructive domain), 0.92 for SCHNOS-C (Cosmetic domain). Spearman correlations for SCHNOS-O (0.36-0.65) and SCHNOS-C (0.51-0.74) were positive and significant. Test-retest reliability analyses revealed strong Spearman correlations for SCHNOS-O (r=0.87) and SCHNOS-C (r=0.90). Responsiveness was statistically significant for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P=0.222). Exploratory factor analysis and parallel tests indicated that C-SCHNOS maintained a single-factor structure, with eigenvalues exceeding the critical values (2.55 for SCHNOS-O and 4.35 for SCHNOS-C), reflecting excellent unidimensionality. CONCLUSIONS: The SCHNOS questionnaire was successfully translated into Chinese and culturally adapted. The C-SCHNOS is a dependable and valid instrument for use in Chinese population undergoing functional or cosmetic rhinoplasty.

9.
Microbiome ; 12(1): 131, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030599

RESUMEN

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.


Asunto(s)
Microbioma Gastrointestinal , Rumen , Destete , Animales , Bovinos , Rumen/microbiología , Rumen/metabolismo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Bacterias/genética , Femenino , Fermentación , Metagenómica/métodos , Metabolómica , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/análisis , Aumento de Peso , Butiratos/metabolismo
10.
Commun Biol ; 7(1): 843, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987326

RESUMEN

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy.


Asunto(s)
Glutatión , Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Glutatión/metabolismo , Humanos , Animales , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Proteínas de Fusión bcr-abl/metabolismo , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/antagonistas & inhibidores
11.
Sci Rep ; 14(1): 16830, 2024 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039227

RESUMEN

Two important factors affecting the progress of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the S-protein binding function of ACE2 receptors and the membrane fluidity of host cells. This study aimed to evaluate the effect of static magnetic field (SMF) on S-protein/ACE2 binding and cellular membrane fluidity of lung cells, and was performed in vitro using a Calu-3 cell model and in vivo using an animal model. The ability of ACE2 receptors to bind to SARS-CoV-2 spike protein on host cell surfaces under SMF stimulation was evaluated using fluorescence images. Host lung cell membrane fluidity was tested using fluorescence polarization to determine the effects of SMF. Our results indicate that 0.4 T SMF can affect binding between S-protein and ACE2 receptors and increase Calu-3 cell membrane fluidity, and that SMF exposure attenuates LPS-induced alveolar wall thickening in mice. These results may be of value for developing future non-contact, non-invasive, and low side-effect treatments to reduce disease severity in COVID-19-invaded lungs.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Pulmón , Fluidez de la Membrana , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , COVID-19/terapia , COVID-19/virología , Enzima Convertidora de Angiotensina 2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Pulmón/patología , Pulmón/metabolismo , Ratones , Humanos , Campos Magnéticos , Línea Celular , Modelos Animales de Enfermedad , Unión Proteica
12.
Heliyon ; 10(13): e34006, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071644

RESUMEN

Progesterone (P4) plays a pivotal role in regulating the cancer progression of various types, including breast cancer, primarily through its interaction with the P4 receptor (PR). In PR-negative breast cancer cells, P4 appears to function in mediating cancer progression, such as cell growth. However, the mechanisms underlying the roles of P4 in PR-negative breast cancer cells remain incompletely understood. This study aimed to investigate the effects of P4 on cell proliferation, gene expression, and signal transduction in PR-negative MDA-MB-231 breast cancer cells. P4-activated genes, associated with proliferation in breast cancer cells, exhibit a stimulating effect on cell growth in PR-negative MDA-MB-231 cells, while demonstrating an inhibitory impact in PR-positive MCF-7 cells. The use of arginine-glycine-aspartate (RGD) peptide successfully blocked P4-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, aligning with computational models of P4 binding to integrin αvß3. Disrupting integrin αvß3 binding with RGD peptide or anti-integrin αvß3 antibody altered P4-induced expression of proliferative genes and modified P4-induced cell growth in breast cancer cells. In conclusion, integrin αvß3 appears to mediate P4-induced ERK1/2 signal pathway to regulate proliferation via alteration of proliferation-related gene expression in PR-negative breast cancer cells.

13.
Neurol Res ; : 1-11, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033031

RESUMEN

OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.

14.
Phys Med Biol ; 69(15)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38959907

RESUMEN

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.


Asunto(s)
Automatización , Neoplasias Pulmonares , Planificación de la Radioterapia Asistida por Computador , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagen , Dosificación Radioterapéutica , Pulmón/efectos de la radiación , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Radioterapia Guiada por Imagen/métodos
15.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38928455

RESUMEN

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.


Asunto(s)
Regeneración Ósea , Células Madre Mesenquimatosas , Osteogénesis , Aceites de Plantas , Sapindus , Semillas , Animales , Conejos , Aceites de Plantas/farmacología , Semillas/química , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Sapindus/química , Diferenciación Celular/efectos de los fármacos , Microtomografía por Rayos X , Ingeniería de Tejidos/métodos , Humanos , Células Cultivadas
16.
Small ; : e2402842, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38923165

RESUMEN

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.

17.
Plants (Basel) ; 13(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38891326

RESUMEN

Cinnamomum osmophloeum Kanehira (CO) is an endemic species of Taiwan. This study elucidated the composition of CO hydrosol, revealing trans-cinnamaldehyde (65.03%), trans-cinnamyl acetate (7.57%), and coumarin (4.31%) as the main volatile compounds. Seven compounds were identified in the water fraction of hydrosol, including a novel compound, 2-(2-hydroxyphenyl)oxetan-3-ol. This marks the first investigation into high-polarity compounds in hydrosol, extending beyond the volatile components. Notably, two compounds, trans-phenyloxetan-3-ol and cis-phenyloxetan-3-ol, demonstrated significant inhibition activity against phosphodiesterase type five (PDE5), with IC50 values of 4.37 µM and 3.40 µM, respectively, indicating their potential as novel PDE5 inhibitors. Furthermore, CO hydrosol was evaluated against enzymes associated with erectile dysfunction, namely acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE), and arginase type 2 (ARG2). These findings underscore the potential of CO hydrosol to modulate erectile function through diverse physiological pathways, hinting at its prospects for future development in a beverage or additive with enhanced effects on erectile function.

18.
Physiol Rep ; 12(11): e16050, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38839736

RESUMEN

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.


Asunto(s)
Antiinflamatorios , Antioxidantes , Ginkgo biloba , Miembro Posterior , Músculo Esquelético , Extractos Vegetales , Daño por Reperfusión , Animales , Ginkgo biloba/química , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Extractos Vegetales/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigación sanguínea , Ratones , Miembro Posterior/irrigación sanguínea , Masculino , Ratas , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Interleucina-6/metabolismo , Ratas Sprague-Dawley , Extracto de Ginkgo
19.
Clin Exp Ophthalmol ; 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853535

RESUMEN

BACKGROUND: This systematic review and meta-analysis quantitatively examines the efficacy of angle-based minimally invasive glaucoma surgery (MIGS) in normal tension glaucoma (NTG). METHODS: A literature search was performed on Medline, Embase, PubMed, CINAHL and Cochrane Library from inception until 20 December 2022. Pilot, cohort, observational studies and randomised controlled trials including at least 5 subjects undergoing angle-based MIGS (trabecular-bypass devices, excisional trabeculotomy, goniotomy and ab-interno canaloplasty) for NTG, with or without cataract surgery, were included. Meta-analysis of continuous outcome using the meta routine in R version 2022.12.0+353 was performed to determine mean intraocular pressure (IOP) and anti-glaucoma medication (AGM) reduction post-operatively. RESULTS: Of the 846 studies initially identified, 15 studies with a pooled total of 367 eyes which underwent combined phacoemulsification and angle-based MIGS were included for final meta-analysis. Outcomes of the iStent were reported in 5 studies, iStent inject in 7 studies, Hydrus Microstent in 1 study, Kahook Dual Blade in 3 studies, and Trabectome in 2 studies. There was significant reduction in both IOP and AGM post-operatively at 6 months (2.44 mmHg, 95%CI: 1.83-3.06; 1.21 AGM, 95%CI: 0.99-1.44), 12 months (2.28 mmHg, 95%CI: 1.71-2.84; 1.18 AGM, 95%CI: 0.90-1.47), 24 months (2.10 mmHg, 95%CI: 1.51-2.68; 1.26 AGM, 95%CI: 0.85-1.68) and 36 months (2.43 mmHg, 95%CI: 1.71-3.15, 0.87 AGM, 95%CI: 0.21-1.53) (all p < 0.05). Subgroup analysis on combined phacoemulsification-iStent inject surgery demonstrated a reduction in both IOP (2.31 mmHg, 95%CI: 1.07-3.56, p < 0.001) and AGM (1.07 AGM, 95%CI: 0.86-1.29, p < 0.001) at 12 months post-operatively. CONCLUSIONS: Angle-based MIGS combined with phacoemulsification effectively reduces IOP and AGM in NTG eyes for up to 36 months after surgery.

20.
Blood Purif ; 53(8): 676-685, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38797161

RESUMEN

INTRODUCTION: This study aimed to identify risk factors affecting outcomes in pediatric patients requiring emergent peritoneal dialysis (PD) for all causes, focusing on survival rates, kidney function recovery, PD duration, complications, and quality of life. METHODS: A retrospective review was conducted on medical records of pediatric patients who received emergent bedside PD in the intensive care unit from January 2010 to February 2023. Thirty-four catheters were placed, with demographic, preoperative, and procedural data collected. MedCalc® Statistical Software was used for analysis with a significance level set at p < 0.05. Prophylactic antibiotics were administered prior to surgery, and catheters were placed using a consistent technique by a single team of pediatric surgeons. RESULTS: The median age at catheter placement was 39 days (range 2-2,286), and the median body weight was 3.53 kg (range 1.2-48.8). The majority were male (64.7%), with 17.6% preterm. The most common indication for PD was acute kidney injury (AKI) (88.2%), followed by hyperammonemia, metabolic acidosis, and abdominal compartment syndrome. The median waiting period for PD placement was 1 day, and the median duration of PD was 7 days. Complications included dialysate leakage (22.8%) and catheter obstruction leading to PD discontinuation (31.4%). The mortality rate was high at 71.4%. CONCLUSION: It is advisable to advocate for the early initiation of PD in pediatric patients following cardiac surgery. AKI is a significant risk factor for mortality, while prematurity increases the risk of dialysate leakage. Omentectomy and the method of catheter exit did not significantly affect outcomes. The study's limitations highlight the need for larger prospective studies to better understand and improve emergent PD management in this vulnerable population.


Asunto(s)
Diálisis Peritoneal , Humanos , Diálisis Peritoneal/métodos , Diálisis Peritoneal/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Lactante , Preescolar , Niño , Recién Nacido , Unidades de Cuidados Intensivos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Factores de Riesgo , Calidad de Vida , Resultado del Tratamiento
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