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1.
Sci Rep ; 14(1): 12427, 2024 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816543

RESUMEN

Intracerebral hemorrhage (ICH) is a common cerebral vascular disease with high incidence, disability, and mortality. Ferroptosis is a regulated type of iron-dependent, non-apoptotic programmed cell death. There is increasing evidence that ferroptosis may lead to neuronal damage mediated by hemorrhagic stroke mediated neuronal damage. Salvianolic acid A (SAA) is a natural bioactive polyphenol compound extracted from salvia miltiorrhiza, which has anti-inflammatory, antioxidant, and antifibrosis activities. SAA is reported to be an iron chelator that inhibits lipid peroxidation and provides neuroprotective effects. However, whether SAA improves neuronal ferroptosis mediated by hemorrhagic stroke remains unclear. The study aims to evaluate the therapeutic effect of SAA on Ferroptosis mediated by Intracerebral hemorrhage and explore its potential mechanisms. We constructed in vivo and in vitro models of intracerebral hemorrhage in rats. Multiple methods were used to analyze the inhibitory effect of SAA on ferroptosis in both in vivo and in vitro models of intracerebral hemorrhage in rats. Then, network pharmacology is used to identify potential targets and mechanisms for SAA treatment of ICH. The SAA target ICH network combines SAA and ICH targets with protein-protein interactions (PPIs). Find the specific mechanism of SAA acting on ferroptosis through molecular docking and functional enrichment analysis. In rats, SAA (10 mg/kg in vivo and 50 µM in vitro, p < 0.05) alleviated dyskinesia and brain injury in the ICH model by inhibiting ferroptosis (p < 0.05). The molecular docking results and functional enrichment analyses suggested that AKT (V-akt murine thymoma viral oncogene homolog) could mediate the effect of SAA. NRF2 (Nuclear factor erythroid 2-related factor 2) was a potential target of SAA. Our further experiments showed that salvianolic acid A enhanced the Akt /GSK-3ß/Nrf2 signaling pathway activation in vivo and in vitro. At the same time, SAA significantly expanded the expression of GPX4, XCT proteins, and the nuclear expression of Nrf2, while the AKT inhibitor SH-6 and the Nrf2 inhibitor ML385 could reduce them to some extent. Therefore, SAA effectively ameliorated ICH-mediated neuronal ferroptosis. Meanwhile, one of the critical mechanisms of SAA inhibiting ferroptosis was activating the Akt/GSK-3ß/Nrf2 signaling pathway.


Asunto(s)
Ácidos Cafeicos , Hemorragia Cerebral , Ferroptosis , Lactatos , Fármacos Neuroprotectores , Animales , Ferroptosis/efectos de los fármacos , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Ratas , Lactatos/farmacología , Lactatos/química , Lactatos/uso terapéutico , Masculino , Fármacos Neuroprotectores/farmacología , Ratas Sprague-Dawley , Factor 2 Relacionado con NF-E2/metabolismo , Simulación del Acoplamiento Molecular , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo
2.
PLoS One ; 19(5): e0303324, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38739623

RESUMEN

BACKGROUND: Scoliosis is one of the most common surgical disorders of the pediatric spine. Refractive errors are commonly associated with vision impairment worldwide. However, it is currently unclear whether refractive error correlates directly with the development of scoliosis. METHODS: A cross-sectional study was performed in 2023, and a stratified cluster sampling technique was employed among school-aged students in Nantong City, China. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between scoliosis and related parameters; various types of refractive errors were also included in the study. RESULTS: The prevalence of scoliosis among school-aged students was 2.2% in Nantong city. Multiple logistic regression analyses showed that myopia, hyperopia, astigmatism, and anisometropia were not correlated with the development of scoliosis (all, p≥0.05). Lower body mass index (BMI) [adjusted odds ratio (aOR) = 0.92; 95% confidence interval (CI): 0.88-0.95; p<0.001], living in rural areas (aOR = 1.40; 95% CI: 1.05-1.86; p = 0.020), and older age (aOR = 1.32; 95% CI: 1.25-1.38; p<0.001) had significantly higher risks of scoliosis. CONCLUSIONS: Refractive errors did not correlate with the development of scoliosis. However, BMI, living in rural areas and older age did correlate with the development of scoliosis.


Asunto(s)
Errores de Refracción , Escoliosis , Escoliosis/epidemiología , Escoliosis/complicaciones , Humanos , Masculino , Femenino , Estudios Transversales , Errores de Refracción/epidemiología , Niño , Adolescente , China/epidemiología , Prevalencia , Factores de Riesgo , Índice de Masa Corporal , Modelos Logísticos
3.
Mol Cell Biochem ; 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459276

RESUMEN

Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-ex) have become a hopeful substitute for whole-cell therapy due to their minimal immunogenicity and tumorigenicity. The present study aimed to investigate the hypothesis that hUCMSC-ex can alleviate excessive inflammation resulting from intracerebral hemorrhage (ICH) and facilitate the rehabilitation of the nervous system in rats. In vivo, hemorrhagic stroke was induced by injecting collagenase IV into the striatum of rats using stereotactic techniques. hUCMSC-ex were injected via the tail vein at 6 h after ICH model establishment at a dosage of 200 µg. In vitro, astrocytes were pretreated with hUCMSC-ex and then stimulated with hemin (20 µmol/mL) to establish an ICH cell model. The expression of TLR4/NF-κB signaling pathway proteins and inflammatory factors, including TNF-α, IL-1ß, and IL-10, was assessed both in vivo and in vitro to investigate the impact of hUCMSC-ex on inflammation. The neurological function of the ICH rats was evaluated using the corner turn test, forelimb placement test, Longa score, and Bederson score on the 1st, 3rd, and 5th day. Additionally, RT-PCR was employed to examine the mRNA expression of TLR4 following hUCMSC-ex treatment. The findings demonstrated that hUCMSC-ex downregulated the protein expression of TLR4, NF-κB/P65, and p-P65, reduced the levels of pro-inflammatory cytokines TNF-α and IL-1ß, and increased the expression of the anti-inflammatory cytokine IL-10. Ultimately, the administration of hUCMSC-ex improved the behavioral performance of the ICH rats. However, the results of PT-PCR indicated that hUCMSC-ex did not affect the expression of TLR4 mRNA induced by ICH, suggesting that hUCMSCs-ex may inhibit TLR4 translation rather than transcription, thereby suppressing the TLR4/NF-κB signaling pathway. We can conclude that hUCMSC-ex mitigates hyperinflammation following ICH by inhibiting the TLR4/NF-κB signaling pathway. This study provides preclinical evidence for the potential future application of hUCMSC-ex in the treatment of cerebral injury.

4.
Toxicol Appl Pharmacol ; 484: 116840, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38307258

RESUMEN

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.


Asunto(s)
Exosomas , ARN Largo no Codificante , Ratas , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Isoproterenol/toxicidad , Redes Reguladoras de Genes , Ratas Sprague-Dawley , Cardiotoxicidad , Exosomas/genética , Exosomas/metabolismo , ARN Mensajero/metabolismo
5.
Hum Reprod ; 38(12): 2412-2421, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37846525

RESUMEN

STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Aborto Espontáneo , Desastres Naturales , Embarazo , Femenino , Humanos , Masculino , Vitrificación , Criopreservación/métodos , Estudios Retrospectivos , Semen , Índice de Embarazo , Oocitos , Desarrollo Embrionario , Fertilización In Vitro
6.
Medicine (Baltimore) ; 102(37): e35084, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37713871

RESUMEN

To explore the expression and prognosis of Fc fragment of IgG low affinity IIb receptor (FCGR2B) in glioma and its relationship with immune microenvironment, so as to provide potential molecular targets for the treatment of glioma. We analyzed the gene expression of FCGR2B using the Cancer Genome Atlas database, Chinese Glioma Genome Atlas, Gene Expression Omnibus database and other glioma related databases. Moreover, we generated survival receiver operating characteristic curve, carried out univariate and multivariate Cox analysis and nomograph construction, and analyzed the relationship between FCGR2B and prognosis. According to the median of FCGR2B gene expression value, the differential expression analysis was carried out by high and low grouping method, and the gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis enrichment analysis were carried out to explore the possible mechanism. Then, the correlation between immune score of glioma and prognosis, World Health Organization grade and FCGR2B expression was analyzed. Finally, the correlation between FCGR2B expression and the proportion of tumor infiltrating immune cells, immune checkpoints, tumor mutation load and immune function was analyzed. The expression of FCGR2B in gliomas was higher than that in normal tissues and was associated with poor prognosis. Independent prognostic analysis showed that FCGR2B was an independent prognostic factor for glioma. The analysis of gene ontology and gene set enrichment analysis showed that FCGR2B was closely related to immune-related functions. The analysis of immune scores and prognosis, World Health Organization grade and FCGR2B expression in gliomas indicated that patients with high immune scores had significantly poorer overall survival and higher tumor pathological grade. In addition, immune scores were significantly positively correlated with the expression of FCGR2B. The analysis of tumor infiltrating immune cells suggested that the expression level of FCGR2B affected the immune activity of TME. In addition, the expression of FCGR2B was positively correlated with almost all immune checkpoint molecules including CD28, CD44, TNFSF14, PDCD1LG2, LAIR1, and CD48 and was significantly positively correlated with tumor mutation load. All immunobiological functions of the high expression group of FCGR2B were significantly inhibited. FCGR2B may play an important role in the occurrence, development and invasion of tumor by influencing the tumor microenvironment of immunosuppression. FCGR2B may be an important target for the treatment of glioma.


Asunto(s)
Glioma , Microambiente Tumoral , Humanos , Pueblo Asiatico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Antígenos CD28 , Glioma/genética , Glioma/inmunología , Pronóstico , Receptores de IgG/genética , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
7.
J Am Chem Soc ; 145(32): 18115-18125, 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37525426

RESUMEN

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

8.
Curr Issues Mol Biol ; 45(6): 4647-4664, 2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37367044

RESUMEN

Citrus (Citrus reticulata) is one of the world's most widely planted and highest-yielding fruit trees. Citrus fruits are rich in a variety of nutrients. The content of citric acid plays a decisive role in the flavor quality of the fruit. There is a high organic acid content in early-maturing and extra-precocious citrus varieties. Reducing the amount of organic acid after fruit ripening is significant to the citrus industry. In this study, we selected a low-acid variety, "DF4", and a high-acid variety, "WZ", as research materials. Through WGCNA analysis, two differentially expressed genes, citrate synthase (CS) and ATP citrate-pro-S-lyase (ACL), were screened out, which related to the changing citric acid. The two differentially expressed genes were preliminarily verified by constructing a virus-induced gene-silencing (VIGS) vector. The VIGS results showed that the citric acid content was negatively correlated with CS expression and positively correlated with ACL expression, while CS and ACL oppositely control citric acid and inversely regulate each other. These results provide a theoretical basis for promoting the breeding of early-maturing and low-acid citrus varieties.

9.
Biology (Basel) ; 11(7)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-36101454

RESUMEN

Citrus aurantium L. (sour orange) is a significant Chinese medicinal and fruit crop rich in flavonoids. However, the pathways and genes involved in flavonoid biosynthesis at the key developmental stages of Citrus aurantium L. are not fully understood. This study found that the total flavonoid concentration gradually decreased as the fruit developed. Additionally, it showed that neohesperidin was the main flavonoid in the early stages of sour orange fruit development. However, as the development stage progressed, naringin content increased rapidly and emerged as the main flavonoid component. From 27 cDNA libraries, RNA sequencing yielded 16.64 billion clean bases, including 8989 differentially expressed genes. We identified 74 flavonoid related unigenes mapped to the phenylalanine, tyrosine, and phenylpropanoid biosynthesis pathways. A total of 152 UDP-glucuronosyltransferase genes (UGTs) were identified from C. aurantium L. transcriptome database, in which 22 key flavonoid-correlated UGTs were divided into five main AtGT groups: E, G, I, L, M. We observed that the ethylene responsive factors (ERF) and myeloblastosis (MYB) family mainly regulated the key genes involved in flavonoid biosynthesis. Overall, our study generated extensive and detailed transcriptome data on the development of C. aurantium L. and characterized the flavonoid biosynthesis pattern during its fruit developmental stages. These results will benefit genetic modification or selection to increase the flavonoid content in sour oranges.

10.
Front Cell Neurosci ; 16: 911973, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928572

RESUMEN

Objective: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease with high incidence, disability, and mortality. Casein kinase 2 (CK2) is a serine/threonine kinase with hundreds of identified substrates and plays an important role in many diseases. This study aimed to explore whether CK2 plays protective roles in ICH-induced neuronal apoptosis, inflammation, and oxidative stress through regulation NR2B phosphorylation. Methods: CK2 expression level of brain tissues taken from ICH patients was determined by immunoblotting. Neurons from embryonic rat and astrocytes from newborn rats were cultured and treated by Hemoglobin chloride (Hemin). The proliferation of astrocytes, the apoptosis and oxidative stress of neurons and the inflammatory factors of astrocytes were detected. CK2 expression was determined in ICH model rats. The effects of CK2 overexpression plasmid (pc-CK2) on neurobehavioral defects and brain water content in ICH rats were observed. Results: CK2 expression in ICH patients was down-regulated. Overexpression of CK2 promoted the astrocyte proliferation, inhibited neuronal apoptosis, and reduced astrocyte-mediated inflammation. N-methyl-D-aspartate receptor 2B (NR2B) reversed the effects of pc-CK2 on neurons and astrocytes. CK2 phosphorylated NR2B at the S1480 site, down-regulated the expression of NR2B and interfered with the interaction between NR2B and postsynaptic density protein 95 (PSD95). In vivo experiments showed that the expression of CK2 decreased and the expression of NR2B increased in ICH rats. Furthermore, pc-CK2 attenuated neurobehavioral defects, brain water content and neuronal damage in ICH rats. Conclusion: CK2 phosphorylated NR2B, down-regulated the expression of NR2B, interfered with the interaction between NR2B and PSD95, alleviated inflammatory reactions, inhibited neuronal apoptosis and oxidative stress after ICH. CK2 and NR2B may be new potential therapeutic targets for the treatment of ICH. However, the limitation of this study is that we only investigated the regulation of NR2B by CK2.

11.
Medicine (Baltimore) ; 101(31): e30026, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35945710

RESUMEN

To investigate the normal diameter of the abdominal aorta and common iliac arteries of the middle-aged and elderly people in China and the relationship of the diameters with age, sex, height, weight, body mass index (BMI), and body surface area (BSA). This retrospective study enrolled 625 patients including 380 males and 245 females aged 60.00 years (interquartile range 13.00 years). All clinical data and the diameters of the abdominal aorta and common iliac arteries were analyzed. The diameter of the abdominal aorta was 21.49 ± 2.49 mm at the proximal, 16.94 (interquartile range 2.39) mm at the middle, and 15.65 (interquartile range 2.90) mm at the distal segment. The diameter of the common iliac artery was 10.76 (interquartile range 1.99) mm at the right proximal, 10.41 (interquartile range 2.05) mm at the left proximal, 10.74 (interquartile range 2.25) mm at the right distal, and 10.67 (interquartile range 2.22) mm at the left distal segment. The height, weight, BSA, BMI, diameters of the proximal, middle and distal abdominal aorta as well as the proximal and distal left and right common iliac arteries were significantly higher in males than those in females (P < .001). Height, weight, BSA, and BMI were significantly (P < .001) positively correlated with the diameter of the abdominal aorta and common iliac artery at the proximal, middle, and distal segments. The middle and distal diameters of the abdominal aorta were significantly higher in males than those in females (P < .05). The diameter of the abdominal aorta at the proximal, middle, and distal segment as well as the diameter of the left and right common iliac artery at the distal segment were significantly (P < .05) increased with age. The normal values of the diameter of the abdominal aorta and common iliac arteries are suggested for the middle-aged and elderly Chinese people for clinical reference. The diameters are gender related and significantly positively correlated with BSA, height, weight, and BMI, which is beneficial for the diagnosis and treatment planning of relevant vascular diseases.


Asunto(s)
Aorta Abdominal , Arteria Ilíaca , Anciano , Aorta Abdominal/diagnóstico por imagen , Superficie Corporal , China , Femenino , Humanos , Arteria Ilíaca/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
12.
Neurochem Res ; 47(10): 3063-3075, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35809188

RESUMEN

Neuroinflammation plays an important role in brain tissue injury during intracerebral hemorrhage. Gabapentin can reduce inflammation and oxidative stress through inhibiting nuclear factor κB (NFκB) signals. Here, we showed that gabapentin reduced brain tissue injury in ICH through suppressing NFκB-mediated neuroinflammation. ICH was induced by injecting collagenase IV into the right striatum of Sprague-Dawley rats. PC12 and BV2 cells injury induced by Hemin were used to simulate ICH in vitro. Inflammation and apoptosis were assessed in rat brain tissue and in vitro cells. The neurobehavioral scores were significantly decreased in ICH rats compared with sham rats. Phosphorylated IκB-α and cleaved caspase3, and apoptosis rate were significantly higher in tissue surrounding the hematoma than in brain tissues from rats subjected to sham surgery. Furthermore, serum IL-6 levels in ICH rats were higher than in sham rats. Gabapentin treatment significantly improved the behavioral scores, decreased levels of phosphorylated IκB-α and cleaved caspase3, apoptosis rate, and serum IL-6 level in ICH rats. Hemin-treated BV2 cells displayed higher levels of phosphorylated IκB-α, cleaved caspase3, and IL-6 in the supernatant compared with vehicle-treated cells. Hemin treatment induced a significantly lower level of peroxisome proliferator-activated receptor γ (PPARγ) in BV2 cells. BV2-PC12 co-culture cells treated by hemin displayed higher levels of cleaved caspase3 in PC12 cells. Furthermore, gabapentin treatment could reduce these effects induced by hemin and the protective effects of gabapentin were significantly attenuated by PPARγ inhibitor. Therefore, gabapentin may reduce inflammation and apoptosis induced by the ICH through PPARγ-NFκB pathway.


Asunto(s)
Lesiones Encefálicas , Hemorragia Cerebral , Gabapentina , Hemina , Animales , Ratas , Apoptosis , Encéfalo/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/etiología , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Gabapentina/uso terapéutico , Hemina/farmacología , Inflamación/tratamiento farmacológico , Interleucina-6/metabolismo , Enfermedades Neuroinflamatorias , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , PPAR gamma/metabolismo , Ratas Sprague-Dawley
13.
Biology (Basel) ; 11(6)2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35741376

RESUMEN

Akebia trifoliata (Thunb.) Koidz is an important Chinese medicinal and economic crop. Its seeds, which are rich in fatty acids, are usually discarded. As of now, A. trifoliata lipid biosynthesis pathways and genes have not been clearly described. In this work, we found that seed and fruit development of A. trifoliata were not synchronized, and that when the fruit was ripe, seed oil content was not at its highest. As seeds developed, linoleic and oleic acid content was found to decrease and increase, respectively. RNA sequencing yielded 108.45 GB of clean reads from 15 cDNA libraries, containing 8756 differentially expressed genes. We identified 65 unigenes associated with lipid biosynthesis, including fatty acid and triacylglycerol biosynthesis. The 65 unigenes were mapped to the A. trifoliata lipid synthesis pathway. There were 20 AtrFAD family members in A. trifoliata, which could be divided into four sub-groups with the highest number of AtrSADs. Our study revealed the dynamic changes in A. trifoliata seed oil content and composition during its growth period and provides large-scale and comprehensive transcriptome data of A. trifoliata seeds. These findings provide a basis for the improvement of A. trifoliata seed oil yield and quality.

14.
Nutr Cancer ; 74(10): 3692-3700, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35639488

RESUMEN

Natural medicinal compounds have gained increasing attention as adjuvants during cancer chemotherapy. The present study demonstrated the chemosensitizing effect of sesamol, a natural phenolic compound, in HeLa cell lines In Vitro. Sesamol-pretreated (10 µM) HeLa cells were exposed to 7.5 nM paclitaxel. The chemosensitization was estimated by MTT-based metabolic assay. Further, oxidative DNA damage, alterations in mitochondrial membrane potential (MMP), and apoptotic morphological changes were analyzed. Sesamol treatment before paclitaxel treatment significantly decreased the IC50 value of paclitaxel (7.5 nM) in a concentration-dependent manner. Further, Sesamol treatment before paclitaxel increased the intracellular ROS levels and enhanced apoptosis through MMP alterations. Moreover, there was an increased % of tail DNA in sesamol + paclitaxel-treated cervical cancer cells compared to paclitaxel alone treatment. The frequency of apoptotic cells were also increased during sesamol + paclitaxel treatment cells compared to paclitaxel alone treatment. Thus, Sesamol treatment before paclitaxel exposure enhanced the apoptotic cell death in the HeLa cell lines. The results of the present study were in support of the usage of natural medicinal compounds for clinical chemotherapy after systematic animal experimentations.


Asunto(s)
Paclitaxel , Neoplasias del Cuello Uterino , Animales , Apoptosis , Benzodioxoles/farmacología , Femenino , Células HeLa , Humanos , Paclitaxel/farmacología , Fenoles , Neoplasias del Cuello Uterino/tratamiento farmacológico
15.
Front Oncol ; 12: 845036, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35494053

RESUMEN

Calcium/calmodulin-dependent protein ID (CAMK1D) is widely expressed in many tissues and involved in tumor cell growth. However, its role in gliomas has not yet been elucidated. This study aimed to investigate the roles of CAMK1D in the proliferation, migration, and invasion of glioma. Through online datasets, Western blot, and immunohistochemical analysis, glioma tissue has significantly lower CAMK1D expression levels than normal brain (NB) tissues, and CAMK1D expression was positively correlated with the WHO classification. Kaplan-Meier survival analysis shows that CAMK1D can be used as a potential prognostic indicator to predict the overall survival of glioma patients. In addition, colony formation assay, cell counting Kit-8, and xenograft experiment identified that knockdown of CAMK1D promotes the proliferation of glioma cells. Transwell and wound healing assays identified that knockdown of CAMK1D promoted the invasion and migration of glioma cells. In the above experiments, the results of overexpression of CAMK1D were all contrary to those of knockdown. In terms of mechanism, this study found that CAMK1D regulates the function of glioma cells by the PI3K/AKT/mTOR pathway. In conclusion, these findings suggest that CAMK1D serves as a prognostic predictor and a new target for developing therapeutics to treat glioma.

16.
Angew Chem Int Ed Engl ; 61(23): e202203835, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35322509

RESUMEN

Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.


Asunto(s)
Compuestos Alílicos , Paladio , Compuestos Alílicos/química , Catálisis , Ésteres/química , Ligandos , Paladio/química , Estereoisomerismo
17.
Environ Sci Pollut Res Int ; 29(32): 49105-49115, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35212897

RESUMEN

The sequencing batch reactor (SBR) activated sludge process is a well-established technology for sewage treatment. One of the drawbacks of SBRs, however, total nitrogen (TN) removals is insufficient. By means of introducing four improvements, including semi-fixed biofilm carrier, sludge elevation mixing and change for the mode of influent and effluent, compliant standard for TN discharge was obtained in this novel SBR configuration during low- and high-strength sewage load. To illustrate the microbial compositions and functions of the attached biofilm on semi-fixed carrier and the suspended aggregates, as well as the nitrogen removal pathway, high throughput 16S rRNA gene amplicon sequencing, PICRUSt2 algorithm, and KEGG database were applied. The results revealed that (i) the microbial communities from suspended aggregates and biofilm samples were significantly different from each other; (ii) during low-strength sewage loads, TN removal was mainly by nitrification-denitrification. The suspended aggregates was responsible for denitrification, while the biofilm was focused on ammonium oxidation; (iii) during high-strength sewage loads, function of nitrate reductase from suspended aggregates was faded, and anammox and N assimilation by biofilm became dominant. Meanwhile, TN removal referring to the formation of L-glutamine via assimilation was the main pathway.


Asunto(s)
Nitrógeno , Aguas del Alcantarillado , Biopelículas , Reactores Biológicos , Desnitrificación , Nitrificación , Oxidación-Reducción , Proyectos Piloto , ARN Ribosómico 16S
18.
Chemosphere ; 286(Pt 2): 131686, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34333184

RESUMEN

Change in water quality was investigated with laboratory-scale ozone-biological activated carbon filters using copper-modified granular activated carbon (Cu/GAC) and unmodified granular activated carbon (GAC). In the first seven days of the experimental period, Cu/GAC removed organic matter more efficiently owing to its enhanced adsorption capacity. As the running time increased, the amount of disinfection by-products (DBPs), dissolved organic carbon, and extracellular polymeric substances (EPS) increased sharply in the effluent of the Cu/GAC filter (CCW). More importantly, the EPS suspended in the CCW exhibited weaker flocculating efficiency and hydrophobicity, causing more active chemical reactions between chlorine and EPS substances. The copper species significantly limited the microbial biomass (0.01 nmol/L adenosine triphosphate) but stimulated the secretion of significant amounts of EPS by microorganisms for self-protection. Furthermore, the microbial community in the bulk water was successfully shaped by Cu/GAC, resulting in a continuous supply of EPS-derived DBP precursors and a sharp rise in chlorine consumption in the downstream drinking water distribution. Therefore, use of modified GAC materials, similar to Cu/GAC, as carrier materials for biological activated carbon (BAC) treatment remains controversial, despite enhanced pollutant adsorption capacity. This is the first study to reveal the mechanism of BAC-modified materials for water quality stability. The study potentially contributes to a comprehensive understanding of the effects of biofilm transformation and microbial community succession on drinking water quality. These results showed that tap water safety risks could be reduced by improving BAC pretreatment in drinking water treatment plants.


Asunto(s)
Agua Potable , Microbiota , Contaminantes Químicos del Agua , Purificación del Agua , Carbón Orgánico , Desinfección , Matriz Extracelular de Sustancias Poliméricas/química , Filtración , Contaminantes Químicos del Agua/análisis , Calidad del Agua
19.
BMC Ophthalmol ; 21(1): 439, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34930170

RESUMEN

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.


Asunto(s)
Catarata , Anciano , Anciano de 80 o más Años , Catarata/epidemiología , China/epidemiología , Humanos , Agudeza Visual
20.
Analyst ; 147(1): 66-71, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34821886

RESUMEN

Lipid droplets (LDs) are dynamic multifunctional organelles that participate in the regulation of many metabolic processes, visualization of which is necessary for biological research. In this work, a series of two-photon responsive fluorescent probes (C-H, C-Br, and C-I) based on carbazole units were designed and synthesized. Thereinto, an iodine-modified carbazole derivative C-I exhibited an exciting lipid droplet targeting ability due to its excellent lipophilicity. Meanwhile, benefiting from its larger Stokes shift and two-photon absorption cross-section, C-I was employed for two-photon confocal laser scanning microscopy (CLSM) and stimulated emission depletion (STED) microscopy imaging to observe LDs more accurately. In addition, given the heavy atom effect, C-I can effectively generate reactive oxygen species (ROS) leading to cancer cell apoptosis under near-infrared light irradiation. Notably, we explained the process of cell apoptosis through in vitro simulation experiments. This study provides a promising platform for visualization of lipid droplets.


Asunto(s)
Gotas Lipídicas , Fotoquimioterapia , Carbazoles , Halógenos , Microscopía Confocal
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