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1.
Discov Oncol ; 15(1): 275, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980440

RESUMEN

BACKGROUND: Osteosarcoma (OS), the most common primary malignant bone tumor, predominantly affects children and young adults and is characterized by high invasiveness and poor prognosis. Despite therapeutic advancements, the survival rate remains suboptimal, indicating an urgent need for novel biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance of LGMN expression and immune cell infiltration in the tumor microenvironment of OS. METHODS: We performed an integrative bioinformatics analysis utilizing the GEO and TARGET-OS databases to identify differentially expressed genes (DEGs) associated with LGMN in OS. We conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to explore the biological pathways and functions. Additionally, we constructed protein-protein interaction (PPI) networks, a competing endogenous RNA (ceRNA) network, and applied the CIBERSORT algorithm to quantify immune cell infiltration. The diagnostic and prognostic values of LGMN were evaluated using the area under the receiver operating characteristic (ROC) curve and Cox regression analysis. Furthermore, we employed Consensus Clustering Analysis to explore the heterogeneity within OS samples based on LGMN expression. RESULTS: The analysis revealed significant upregulation of LGMN in OS tissues. DEGs were enriched in immune response and antigen processing pathways, suggesting LGMN's role in immune modulation within the TME. The PPI and ceRNA network analyses provided insights into the regulatory mechanisms involving LGMN. Immune cell infiltration analysis indicated a correlation between high LGMN expression and increased abundance of M2 macrophages, implicating an immunosuppressive role. The diagnostic AUC for LGMN was 0.799, demonstrating its potential as a diagnostic biomarker. High LGMN expression correlated with reduced overall survival (OS) and progression-free survival (PFS). Importantly, Consensus Clustering Analysis identified two distinct subtypes of OS, highlighting the heterogeneity and potential for personalized medicine approaches. CONCLUSIONS: Our study underscores the prognostic value of LGMN in osteosarcoma and its potential as a therapeutic target. The identification of LGMN-associated immune cell subsets and the discovery of distinct OS subtypes through Consensus Clustering Analysis provide new avenues for understanding the immunosuppressive TME of OS and may aid in the development of personalized treatment strategies. Further validation in larger cohorts is warranted to confirm these findings.

2.
bioRxiv ; 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38903071

RESUMEN

The cross-regulation of metabolism and trafficking is not well understood for the vital sphingolipids and cholesterol constituents of cellular compartments. While reports are starting to surface on how sphingolipids like sphingomyelin (SM) dysregulate cholesterol levels in different cellular compartments (Jiang et al., 2022), limited research is available on the mechanisms driving the relationship between sphingolipids and cholesterol homeostasis, or its biological implications. Previously, we have identified sphingolipid metabolism as a unique vulnerability for IDH1 mut gliomas via a rational drug design. Herein, we show how modulating sphingolipid levels affects cholesterol homeostasis in brain tumors. However, we unexpectedly discovered for the first time that C17 sphingosine and NDMS addition to cancer cells alters cholesterol homeostasis by impacting its cellular synthesis, uptake, and efflux leading to a net decrease in cholesterol levels and inducing apoptosis. Our results reflect a reverse correlation between the levels of sphingosines, NDMS, and unesterified, free cholesterol in the cells. We show that increasing sphingosine and NDMS (a sphingosine analog) levels alter not only the trafficking of cholesterol between membranes but also the efflux and synthesis of cholesterol. We also demonstrate that despite the effort to remove free cholesterol by ABCA1-mediated efflux or by suppressing machinery for the influx (LDLR) and biosynthetic pathway (HMGCR), apoptosis is inevitable for IDH1 mut glioma cells. This is the first study that shows how altering sphingosine levels directly affects cholesterol homeostasis in cancer cells and can be used to manipulate this relationship to induce apoptosis in IDH1 mut gliomas.

3.
bioRxiv ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38903086

RESUMEN

Oligodendroglioma is genetically defined as a tumor harboring isocitrate dehydrogenase 1 or 2 mutations (IDH1 mut /IDH2 mut ) and 1p/19q co-deletions. Previously, we reported that in IDH1 mut gliomas, D-2HG, the product of IDH1 mutant enzyme produces an increase in monounsaturated fatty acid levels that are incorporated into ceramides, tilting the S1P-to-ceramide rheostat toward apoptosis. Herein, we exploited this imbalance to further induce and IDH mut -specific glioma cell death. We report for the first time that the inhibition of acid ceramidase (AC) induces apoptosis and provides a benefit in mice survival in IDH1 mut oligodendroglioma. We demonstrated an IDH1 mut -specific cytotoxicity of SABRAC, an irreversible inhibitor of AC, in patient-derived oligodendroglioma cells. Exploring the mechanism of action of this drug, we found that SABRAC activates both extrinsic and intrinsic apoptosis in an ER stress-independent manner, pointing to a direct action of AC-related ceramides in mitochondria permeability. The activation of apoptosis detected under SABRAC treatment was associated with up to 30-fold increase in some ceramide levels and its derivatives from the salvage pathway. We propose that this novel enzyme, AC, has the potential to increase survival in oligodendroglioma with IDH1 mut and should be considered in the future.

4.
Opt Express ; 32(8): 13597-13613, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859326

RESUMEN

The hard X-ray nanoprobe beamline is the first beamline to take advantage of the full coherent beam to attain the nanoscale focusing at the Shanghai Synchrotron Radiation Facility (SSRF). Here we introduce the beamline and specially go over the features of the multilayer Kirkpatrick-Baez focusing system and its supporting phase compensator system. The performance and stability of the phase compensator are also put to the test. By using the speckle scanning metrology, the wavefront of a focused beam was characterized and intensity distribution near the focus was reconstructed. The focusing performance was greatly enhanced by two phase compensations based on a global optimization technique, and a two-dimensional focal spot of 26 nm × 17 nm was achieved and maintained with good stability.

5.
Environ Pollut ; 357: 124404, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908674

RESUMEN

In recent years, there has been a significant increase in surface ozone (O3) concentrations in the troposphere. Ozone pollution has significant adverse effects on ecosystems, human health, and climate change, particularly on crop growth and yield. This study utilized the observational hourly O3 data, cumulative O3 concentration over 40 ppb per h (AOT40), and the mean daytime 7-h O3 concentration (M7) to analyze the spatiotemporal distributions of relative yield losses (RYLs) and evaluate the yield reduction and economic losses of rice in Sichuan province from 2015 to 2020. The results indicated that the average O3 concentration during the growing rice season ranged from 55.4 to 69.3 µg/m3, with the highest O3 concentration observed in 2017, and the AOT40 ranged from 4.5 to 8.7 ppm h from 2015 to 2020. At the county level, the O3 concentration, AOT40, and the relative yield loss (RYL) of rice based on AOT40 exhibited clear spatiotemporal differences in Sichuan. The RYLs of AOT40 were 4.9-9.2% from 2015 to 2020. According to AOT40 and M7 metrics, the yield loss and economic losses attributed to O3 pollution amounted to 78.75-150.36 (9.74-21.54) ten thousand tons, and 2079.08-4149.89 (257.25-594.45) million Yuan, respectively. Rice yield and economic losses were relatively large in the Chengdu Plain, southern Sichuan, and northeast Sichuan. These findings will contribute to a deeper understanding of the detrimental effects of elevated surface O3 concentrations on rice crops. It is imperative to implement more stringent O3 reduction measures aimed at lowering O3 concentrations, enhancing rice quality, and safeguarding food security in Sichuan.

6.
Small Methods ; : e2400178, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686689

RESUMEN

Reversible solid oxide cells (rSOCs) have significant potential as efficient energy conversion and storage systems. Nevertheless, the practical application of their conventional air electrodes, such as La0.8Sr0.2MnO3-δ (LSM), Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), and PrBa0.8Ca0.2Co2O5+δ (PBCC), remains unsatisfactory due to interface delamination during prolonged electrochemical operation. Using micro-focusing X-ray absorption spectroscopy (µ-XAS), a decrease (increase) in the co-valence state from the electrode surface to the electrode/electrolyte interface is observed, leading to the above delamination. Utilizing the one-pot method to incorporate an oxygen-vacancy-enriched CeO2 electrode into these air electrodes, the uniform distribution of the Co valence state is observed, alleviating the structural delamination. PBCC-CeO2 electrodes exhibited a degradation rate of 0.095 mV h-1 at 650 °C during a nearly 500-h test as compared with 0.907 mV h-1 observed during the 135-h test for PBCC. Additionally, a remarkable increase in electrolysis current density from 636 to 934 mA cm-2 under 1.3 V and a maximum power density from 912 to 989 mW cm-2 upon incorporating CeO2 into PBCC is also observed. BSCF-CeO2 and LSM-CeO2 also show enhanced electrochemical performance and prolonged stability as compared to BSCF and LSM. This work offers a strategy to mitigate the structural delamination of conventional electrodes to boost the performance of rSOCs.

7.
Am J Cancer Res ; 14(2): 562-584, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455403

RESUMEN

Previous studies reported that alternating electric fields (EFs) in the intermediate frequency (100-300 kHz) and low intensity (1-3 V/cm) regime - termed "Tumor Treating Fields" (TTFields) - have a specific, anti-proliferative effect on glioblastoma multiforme (GBM) cells. However, the mechanism(s) of action remain(s) incompletely understood, hindering the clinical adoption of treatments based on TTFields. To advance the study of such treatment in vitro, we developed an inductive device to deliver EFs to cell cultures which improves thermal and osmolar regulation compared to prior devices. Using this inductive device, we applied continuous, 200 kHz electromagnetic fields (EMFs) with a radial EF amplitude profile spanning 0-6.5 V/cm to cultures of primary rat astrocytes and several human GBM cell lines - U87, U118, GSC827, and GSC923 - for a duration of 72 hours. Cell density was assessed via segmented pixel densities from GFP expression (U87, U118) or from staining (astrocytes, GSC827, GSC923). Further RNA-Seq analyses were performed on GSC827 and GSC923 cells. Treated cultures of all cell lines exhibited little to no change in proliferation at lower EF amplitudes (0-3 V/cm). At higher amplitudes (> 4 V/cm), different effects were observed. Apparent cell densities increased (U87), decreased (GSC827, GSC923), or showed little change (U118, astrocytes). RNA-Seq analyses on treated and untreated GSC827 and GSC923 cells revealed differentially expressed gene sets of interest, such as those related to cell cycle control. Up- and down-regulation, however, was not consistent across cell lines nor EF amplitudes. Our results indicate no consistent, anti-proliferative effect of 200 kHz EMFs across GBM cell lines and thus contradict previous in vitro findings. Rather, effects varied across different cell lines and EF amplitude regimes, highlighting the need to assess the effect(s) of TTFields and similar treatments on a per cell line basis.

8.
J Asthma ; 61(7): 707-716, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38315158

RESUMEN

Background: The prevalence of childhood asthma and obesity is increasing, while obesity increases the risk and severity of asthma. Lipid metabolism has been considered as an important factor in the pathogenesis of obesity-associated asthma. Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that catalyzes the production of monounsaturated fatty acids (MUFA).Methods: In the present study, the microarray data retrieved from the Gene Expression Comprehensive Database (GEO) was analyzed to further clarify the impact of SCD1 on Mast cell activation related lipid mediators and the correlation between SCD1 and obesity asthma in the population.Results: SCD1 was highly expressed in IgE-activated bone marrow-derived mast cells (BMMCs). Meanwhile, SCD1 was also verified expressed highly in dinitrophenyl human serum albumin (DNP-HAS) stimulated RBL-2H3 cells. The expression of SCD1 was up-regulated in peripheral blood leukocytes of asthmatic children, and was positively correlated with skinfold thickness of upper arm, abdominal skinfold and body mass index (BMI). Inhibition of SCD1 expression significantly suppressed the degranulation, lipid mediator production, as well as the migration ability in DNP-HAS-stimulated RBL-2H3 cells.Conclusion: SCD1 is involved in obese-related asthma through regulating mast cells.


Asunto(s)
Asma , Mastocitos , Estearoil-CoA Desaturasa , Estearoil-CoA Desaturasa/metabolismo , Estearoil-CoA Desaturasa/genética , Mastocitos/inmunología , Mastocitos/metabolismo , Humanos , Niño , Asma/inmunología , Asma/metabolismo , Masculino , Femenino , Animales , Ratones , Obesidad/metabolismo , Ratas , Índice de Masa Corporal
9.
Neurooncol Adv ; 6(1): vdad164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38292240

RESUMEN

Background: Gliosarcoma, an isocitrate dehydrogenase wildtype (IDH-WT) variant of glioblastoma, is defined by clonal biphasic differentiation into gliomatous and sarcomatous components. While the transformation from a glioblastoma to gliosarcoma is uncommon, the subsequent transformation to osteosarcoma is rare but may provide additional insights into the biology of these typically distinct cancers. We observed a patient initially diagnosed with glioblastoma, that differentiated into gliosarcoma at recurrence, and further evolved to osteosarcoma at the second relapse. Our objective was to characterize the molecular mechanisms of tumor progression associated with this phenotypic transformation. Methods: Tumor samples were collected at all 3 stages of disease and RNA sequencing was performed to capture their transcriptomic profiles. Sequential clonal evolution was confirmed by the maintenance of an identical PTEN mutation throughout the tumor differentiation using the TSO500 gene panel. Publicly available datasets and the Nanostring nCounter technology were used to validate the results. Results: The glioblastoma tumor from this patient possessed mixed features of all 3 TCGA-defined transcriptomic subtypes of an IDH-WT glioblastoma and a proportion of osteosarcoma signatures were upregulated in the original tumor. Analysis showed that enhanced transforming growth factor-ß (TGF-ß) and bone morphogenic protein signaling was associated with tumor transformation. Regulatory network analysis revealed that TGF-ß family signaling committed the lineage tumor to osteogenesis by stimulating the expression of runt-related transcription factor 2 (RUNX2), a master regulator of bone formation. Conclusions: This unusual clinical case provided an opportunity to explore the modulators of longitudinal sarcomatous transformation, potentially uncovering markers indicating predisposition to this change and identification of novel therapeutic targets.

10.
Adv Sci (Weinh) ; 11(2): e2304146, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38010981

RESUMEN

Conversion-type electrodes offer a promising multielectron transfer alternative to intercalation hosts with potentially high-capacity release in batteries. However, the poor cycle stability severely hinders their application, especially in aqueous multivalence-ion systems, which can fundamentally impute to anisotropic ion diffusion channel collapse in pristine crystals and irreversible bond fracture during repeated conversion. Here, an amorphous bismuth sulfide (a-BS) formed in situ with unprecedentedly self-controlled moderate conversion Cu2+ storage is proposed to comprehensively regulate the isotropic ion diffusion channels and highly reversible bond evolution. Operando synchrotron X-ray diffraction and substantive verification tests reveal that the total destruction of the Bi─S bond and unsustainable deep alloying are fully restrained. The amorphous structure with robust ion diffusion channels, unique self-controlled moderate conversion, and high electrical conductivity discharge products synergistically boosts the capacity (326.7 mAh g-1 at 1 A g-1 ), rate performance (194.5 mAh g-1 at 10 A g-1 ), and long-lifespan stability (over 8000 cycles with a decay rate of only 0.02 ‰ per cycle). Moreover, the a-BS Cu2+ ‖Zn2+ hybrid ion battery can well supply a stable energy density of 238.6 Wh kg-1 at 9760 W kg-1 . The intrinsically high-stability conversion mechanism explored on amorphous electrodes provides a new opportunity for advanced aqueous storage.

11.
Injury ; 55(2): 111207, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37984015

RESUMEN

Calcaneal tuberosity avulsion fracture, an extra-articular injury, is a rare fracture caused internally by Achilles tendon driven following intense contraction of gastrocnemius-soleus complex, and externally by low-energy (possibly high-energy). Moreover, the risk of injuries of the skin and Achilles tendon around calcaneal tuberosity is closely related to Lee classification and Carnero-Martín de Soto Classification of calcaneal tuberosity avulsion fracture. Although the diagnosis confirmed by X-ray, digital imaging and computed tomography (CT), magnetic resonance imaging (MRI) should also be used to evaluate soft tissue. In recent years, the understanding of this fracture has witnessed the development of different internal fixation devices and surgical procedures. These advances have been further elaborated scientifically in terms of their ability to provide stable fracture reduction ad resistance to Achilles tendon forces. In order to obtain a comprehensive knowledge of the disease, this article reviewed the new understanding of the anatomy, typing, risk factors, and treatment modalities of calcaneal tuberosity avulsion fracture in recent years.


Asunto(s)
Calcáneo , Fracturas por Avulsión , Fracturas Óseas , Humanos , Fracturas por Avulsión/diagnóstico por imagen , Fracturas por Avulsión/cirugía , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas Óseas/patología , Fijación de Fractura , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Calcáneo/lesiones , Músculo Esquelético/patología , Fijación Interna de Fracturas
12.
BMC Pediatr ; 23(1): 534, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884926

RESUMEN

BACKGROUND: Vitamin D deficiency (VDD) is a public health problem. The variation in vitamin D status across regions and populations remains unclear, and there is a lack of consensus regarding the screening for VDD in individuals. METHODS: Children who visited the hospital from January 2019 to December 2020 were included in this study. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using an enzyme-linked immunosorbent assay. The cutoffs for serum 25(OH)D concentrations to define deficiency, insufficiency, and sufficiency were < 20 ng/mL, 20-30 ng/mL, and ≥ 30 ng/mL, respectively. RESULTS: A total of 7285 children aged 0-11 years were assessed; the mean 25(OH)D level was 31.4 ng/mL, and the median 25(OH)D level was 30.7 (interquartile range 24.4, 37.5) ng/mL. The 25(OH)D level declined with age in clinical visiting children aged 0-11 years, but maintained a consistently high level in health examination children aged 4-11 years. The percentages of 25(OH)D < 20 ng/mL and 25(OH)D < 30 ng/mL were 10.0% and 43.8%, respectively. Higher percentages of VDD were found in clinical visiting children than in health examination children within the 6-11-year group (53.3% vs. 14.7%) and winter (44.3% vs. 15.4%). CONCLUSION: Low vitamin D status (deficiency and insufficiency) was more common in clinic-visiting children than in health examinations, especially in schoolchildren and in the winter. The study implies the positive effects of vitamin D assessments included in child health checkups to optimize vitamin D status.


Asunto(s)
Deficiencia de Vitamina D , Vitamina D , Niño , Lactante , Humanos , Estudios Transversales , China/epidemiología , Prevalencia , Vitaminas , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología
13.
Curr Res Toxicol ; 5: 100123, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37731942

RESUMEN

Intracerebral hemorrhage (ICH) refers to severe stroke subtype that may be life-threatening or even cause death. It is clinically observed that coronavirus disease 2019 (COVID-19) may be associated with the high mortality in ICH patients. Ferulic acid, one of the functional bioactive ingredients from medicinal herbs, has been preclinically proven with beneficial activities, including neuroprotection and anti-inflammation actions. Based on current findings, we assumed that ferulic acid may play the potentials against COVID-19 when ICH. In this study, preclinical approach including network pharmacology and molecular docking was applied to detect and identify the core targets and pharmacological mechanisms involved in ferulic acid on COVID-19 and ICH. The network pharmacology analysis identified total eleven core targets in ferulic acid and COVID-19/ICH. The molecular mechanisms of ferulic acid against COVID-19 and ICH were mostly involved in induction of antiviral activity, modulation of inflammatory reaction. Molecular docking model revealed that ferulic acid might effectively bind to epidermal growth factor receptor (EGFR) protein based on strong binding capability. Current findings reflected the preclinical pharmacological activities of ferulic acid that might use for management of COVID-19 and ICH. Although there are the limitations that are absence of experimental validation, these bioinformatic results underline that ferulic acid may exert simultaneous potentials against COVID-19 and ICH through modulating integrative mechanisms and key biotargets.

14.
Mol Biol Rep ; 50(9): 7263-7274, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37422539

RESUMEN

BACKGROUND: Rice stripe virus (RSV) caused a serious disease pandemic in rice in East China between 2001 and 2010. The continuous integrated managements reduced virus epidemic year by year until it was non-epidemic. As an RNA virus, its genetic variability after undergoing a long-term non-epidemic period was meaningful to study. While in 2019, the sudden occurrence of RSV in Jiangsu provided an opportunity for the study. METHODS AND RESULTS: The complete genome of JY2019, an RSV isolate from Jiangyan, was determined. A genotype profile of 22 isolates from China, Japan and Korea indicated that the isolates from Yunnan formed the subtype II, and other isolates clustered the subtype I. RNA 1-3 of JY2019 isolate well-clustered in the subtype I clade, and RNA 4 was also in subtype I, but it had a slight separation from other intra-group isolates. After phylogenetic analyses, it was considered NSvc4 gene contributed to the tendency, because it exhibited an obvious trend towards the subtype II (Yunnan) group. High sequence identity (100%) of NSvc4 between JY2019 and barnyardgrass isolate from different regions demonstrated genetic variation of NSvc4 was consistent in RSV natural populations in Jiangsu in the non-epidemic period. In the phylogenetic tree of all 74 NSvc4 genes, JY2019 belonged to a minor subtype Ib, suggesting the subtype Ib isolates might have existed in natural populations before the non-epidemic period, but not a dominant population. CONCLUSIONS: Our results suggested that NSvc4 gene was susceptible to selection pressure, and the subtype Ib might be more adaptable for the interaction between RSV and hosts in the non-epidemic ecological conditions.


Asunto(s)
Oryza , Tenuivirus , Tenuivirus/genética , Filogenia , Pandemias , China/epidemiología , ARN , Oryza/genética
15.
Food Sci Nutr ; 11(6): 3111-3120, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37324927

RESUMEN

The variation in vitamin D status is still unclear. We aim to describe the vitamin D status among healthy infants and children in Shanghai (31° N latitude), one of the largest cities in China. We conducted a hospital-based, 2-year retrospective observational study and recruited children for health examination at the Tongren Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 2019 to December 2020. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using an enzyme-linked immunosorbent assay. A total of 6164 children aged 0-11 years were included. Of these, 94.4% of the serum 25(OH)D measurements at first assessment were within the range of 12-50 ng/mL. The median 25(OH)D level was 31.3 (IQR 25.6, 38.1) ng/mL, the percentages of 25(OH)D < 20 ng/mL and 25(OH)D < 30 ng/mL were 10.0% and 43.8%, respectively. Low vitamin D status (deficiency and insufficiency) differed significantly by age group (infants, toddlers, preschoolers, and schoolers) and seasonality (all p < .001), but not by gender. For the sub-group (n = 855) of children with repeated assessments, their low 25(OH)D levels increased significantly whether after about a 7-month (n = 351) or 12-month (n = 504) interval, and the increments of median 25(OH)D levels were 8.1 ng/mL and 2.1 ng/mL respectively (p < .001). This study documents the vitamin D status in Shanghai, showing that low vitamin D status is common in infants and children and suggesting that the assessment of 25(OH)D level is necessary for individuals who are at risk for deficiency or excess.

16.
Exp Neurol ; 367: 114449, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37257715

RESUMEN

Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death. Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases. LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease. However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway. Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N-acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl2-induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.


Asunto(s)
Lesiones Encefálicas , Hipoxia-Isquemia Encefálica , Neuroblastoma , Enfermedades Neurodegenerativas , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Pez Cebra/metabolismo , Estrés Oxidativo , Oxígeno/farmacología , Transducción de Señal , Apoptosis , Glucosa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Isquemia
17.
World Neurosurg ; 175: e790-e795, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37061033

RESUMEN

PURPOSE: This study aimed to evaluate the safety and efficacy of microvascular reconstruction combined with decompressive craniectomy (DHC) in patients with malignant middle cerebral artery infarctions (MMCA). METHODS: We searched for patients with MMCA and aged<60 years old, postoperative survival of more than 3 months, consistent with decompression of bone flap removal. Patients were divided into experimental group and control group according to whether they underwent emergency vascular revascularization within 5 days after onset of ischemic stroke. RESULTS: A total of sixpatients were included in the treatment group and 12 patients in the control group. The National Institutes of Health Stroke Scale (NIHSS) score of the treatment group was lower than that of the control group seven days after operation, but the difference was not statistically significant; 3 months after surgery, modified ranking scale (mRs) score in the treatment group was lower than that in the control group, the difference was statistically significant (P = 0.002); mRs scores of the treatment group 3 months after surgery were significantly different from those before surgery (P < 0.05), but no such difference was found in the control group. CONCLUSION: Compared with decompressive craniectomy, open surgical revascularization can improve early cerebral perfusion in MMCA patients, and neurological recovery is better at 3 months after operation. By ensuring that surgeons are properly trained and hospitals are equipped, open surgical revascularization can be a treatment option for patients with MMCA.


Asunto(s)
Craniectomía Descompresiva , Accidente Cerebrovascular Isquémico , Humanos , Persona de Mediana Edad , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/cirugía
18.
Biosci Rep ; 43(2)2023 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-36734979

RESUMEN

The occurrence and development of many diseases are highly associated with the aging of the body. Among them, osteoporosis (OP) is a common age-related disease that tends to occur in the elderly population and is highly related to the aging factors in the body. In the process of aging transmission, the senescence-related secretory phenotype (SASP) can convey the information about aging through the paracrine pathway and endocrine mechanism through the extracellular vesicles (EVs) connected to SASP. EVs can be used as a way of conduction to join the connection between micro-environmental aging and age-related illnesses. EVs are double-layer membranous vesicles separated or secreted from the cell membrane, which mainly include microvesicles (MVs) and exosomes. Vesicular bodies secreted by this exocrine form carry a variety of cell-derived related substances (including a variety of proteins, lipids, DNA, mRNA, miRNAs, etc). These substances are mainly concentrated in human body fluids, especially can be transported to all parts of the body with the blood circulation system, and participate in the interactions between cells. Osteoporosis is closely associated with aging and aging cells, suggesting EVs were active in this pathological process. In this article, the basic mechanisms of aging cells in the occurrence and progression of osteoporosis through EVs will be discussed, to explore the connection between aging and osteoporosis, thereby providing a new perspective on the occurrence and development as well as prevention and treatment of osteoporosis.


Asunto(s)
Micropartículas Derivadas de Células , Exosomas , Vesículas Extracelulares , Osteoporosis , Anciano , Humanos , Vesículas Extracelulares/metabolismo , Senescencia Celular , Exosomas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Osteoporosis/metabolismo
19.
bioRxiv ; 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36789415

RESUMEN

Previous studies reported that alternating electric fields (EFs) in the intermediate frequency (100 - 300 kHz) and low intensity (1 - 3 V/cm) regime - termed "Tumor Treating Fields" (TTFields) - have a specific, anti-proliferative effect on glioblastoma multiforme (GBM) cells. However, the mechanism(s) of action remain(s) incompletely understood, hindering the clinical adoption of treatments based on TTFields. To advance the study of such treatment in vitro , we developed an inductive device to deliver EFs to cell cultures which improves thermal and osmolar regulation compared to prior devices. Using this inductive device, we applied continuous, 200 kHz electromagnetic fields (EMFs) with a radial EF amplitude profile spanning 0 - 6.5 V/cm to cultures of primary rat astrocytes and several human GBM cell lines - U87, U118, GSC827, and GSC923 - for a duration of 72 hours. Cell density was assessed via segmented pixel densities from GFP expression (U87, U118) or from staining (astrocytes, GSC827, GSC923). Further RNA-Seq analyses were performed on GSC827 and GSC923 cells. Treated cultures of all cell lines exhibited little to no change in proliferation at lower EF amplitudes (0 - 3 V/cm). At higher amplitudes (> 4 V/cm), different effects were observed. Apparent cell densities increased (U87), decreased (GSC827, GSC923), or showed little change (U118, astrocytes). RNA-Seq analyses on treated and untreated GSC827 and GSC923 cells revealed differentially expressed gene sets of interest, such as those related to cell cycle control. Up- and down-regulation, however, was not consistent across cell lines nor EF amplitudes. Our results indicate no consistent, anti-proliferative effect of 200 kHz EMFs across GBM cell lines and thus contradict previous in vitro findings. Rather, effects varied across different cell lines and EF amplitude regimes, highlighting the need to assess the effect(s) of TTFields and similar treatments on a per cell line basis.

20.
Jt Dis Relat Surg ; 34(1): 42-49, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36700262

RESUMEN

OBJECTIVES: In this meta-analysis, we aimed to compare the differences in surgical site infection (SSI) between triclosan-coated and uncoated sutures after hip and knee arthroplasty. MATERIALS AND METHODS: We searched PubMed, Embase, and Cochrane databases for randomized-controlled studies (RCTs) comparing triclosan-coated sutures with uncoated sutures for the prevention of SSIs after hip and knee arthroplasty. Literature screening and data curation were performed according to inclusion and exclusion criteria and the risk of bias was assessed for included research using Cochrane Handbook criteria. RESULTS: Three RCTs with a total of 2,689 cases were finally included, including 1,296 cases in the triclosan-coated suture group and 1,393 cases in the control group. The overall incidence of SSI was lower in the group with triclosan antimicrobial sutures (1.9%) than in the uncoated suture group (2.5%), but the difference was statistically significant (odds ratio=0.76, 95% confidence interval: [0.45-1.27], p=0.30). The differences in the results of the incidence of superficial SSI and deep SSI were not statistically significant (p>0.05). CONCLUSION: The application of triclosan antimicrobial sutures did not reduce the incidence of SSI after hip and knee arthroplasty compared to the controls, and it needs further high-quality RCT studies to be improved.


Asunto(s)
Antiinfecciosos Locales , Antiinfecciosos , Triclosán , Humanos , Triclosán/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Suturas/efectos adversos
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