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1.
Bioconjug Chem ; 35(5): 604-615, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38661725

RESUMEN

Chimeric antigen receptor T-cell (CAR-T cell) therapy has become a promising treatment option for B-cell hematological tumors. However, few optional target antigens and disease relapse due to loss of target antigens limit the broad clinical applicability of CAR-T cells. Here, we conjugated an antibody (Ab) fusion protein, consisting of an Ab domain and a SpyCatcher domain, with the FITC-SpyTag (FITC-ST) peptide to form a bispecific safety switch module using a site-specific conjugation system. We applied the safety switch module to target CD19, PDL1, or Her2-expressing tumor cells by constructing FMC63 (anti-CD19), antiPDL1, or ZHER (anti-Her2)-FITC-ST, respectively. Those switch modules significantly improved the cytotoxic effects of anti-FITC CAR-T cells on tumor cells. Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.


Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Animales , Inmunoterapia Adoptiva/métodos , Ratones , Receptores Quiméricos de Antígenos/inmunología , Antígenos CD19/inmunología , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Receptor ErbB-2/inmunología
2.
Lipids Health Dis ; 23(1): 180, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862993

RESUMEN

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.


Asunto(s)
Autofagia , Barrera Hematotesticular , Busulfano , Caprilatos , Estrés Oxidativo , Células de Sertoli , Espermatogénesis , Masculino , Animales , Barrera Hematotesticular/efectos de los fármacos , Barrera Hematotesticular/metabolismo , Busulfano/efectos adversos , Caprilatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratones , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Humanos , Espermatogénesis/efectos de los fármacos , Autofagia/efectos de los fármacos , Infertilidad Masculina/tratamiento farmacológico , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/patología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Adulto
3.
J Neuroinflammation ; 20(1): 82, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36944982

RESUMEN

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.


Asunto(s)
Accidente Cerebrovascular Hemorrágico , Neuralgia , Accidente Cerebrovascular , Ratas , Animales , Hiperalgesia/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Accidente Cerebrovascular Hemorrágico/complicaciones , Accidente Cerebrovascular Hemorrágico/patología , Depresión/etiología , Depresión/terapia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ganglio Estrellado/metabolismo , Ganglio Estrellado/patología , Ratas Sprague-Dawley , Accidente Cerebrovascular/patología , Tálamo/metabolismo , Hemorragia Cerebral/patología , Neuralgia/metabolismo , Ansiedad , Colagenasas/metabolismo , Citocinas/metabolismo
4.
Reprod Biomed Online ; 47(4): 103238, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37573751

RESUMEN

RESEARCH QUESTION: Is early embryo development in mice influenced by RNA binding protein with multiple splicing 2 (RBPMS2), a maternal factor that accumulates and is stored in the cytoplasm of mature oocytes? DESIGN: The expression patterns of RBPMS2 in mouse were analysed using quantitative real-time PCR (qRT PCR) and immunofluorescence staining. The effect of knockdown of RBPMS2 on embryo development was evaluated through a microinjection of specific morpholino or small interfering RNA. RNA sequencing was performed for mechanistic analysis. The interaction between RBPMS2 and the bone morphogenetic protein (BMP) pathway was studied using BMP inhibitor and activator. The effect on the localization of E-cadherin was determined by immunofluorescence staining. RESULTS: Maternal protein RBPMS2 is highly expressed in mouse oocytes, and knockdown of RBPMS2 inhibits embryo development from the morula to the blastocyst stage. Mechanistically, RNA sequencing showed that the differentially expressed genes were enriched in the transforming growth factor-ß (TGF-ß) signalling pathway. BMPs are members of the TGF-ß superfamily of growth factors. It was found that the addition of BMP inhibitor to the culture medium led to a morula-stage arrest, similar to that seen in RBPMS2 knockdown embryos. This morula-stage arrest defect caused by RBPMS2 knockdown was partially rescued by BMP activator. Furthermore, the localization of E-cadherin to the membrane was impaired in response to a knockdown of RBPMS2 or inhibition of the BMP pathway. CONCLUSION: This study suggests that RBPMS2 activates the BMP pathway and thus influences the localization of E-cadherin, which is important for early mouse embryo development during blastocyst formation.


Asunto(s)
Proteínas Morfogenéticas Óseas , Desarrollo Embrionario , Animales , Ratones , Blastocisto/metabolismo , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Desarrollo Embrionario/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
5.
J Org Chem ; 88(9): 5982-5996, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37079849

RESUMEN

A highly selective and divergent synthesis which enabled access to various complex compounds is highly attractive in organic synthesis and medicinal chemistry. Herein, we developed an effective method for divergent synthesis of highly substituted tetrahydroquinolines via Lewis base catalyzed switchable annulations of Morita-Baylis-Hillman carbonates with activated olefins. The reaction displayed switchable [4 + 2] or [3 + 2] annulations via catalyst or substrate control, providing a diverse range of architectures which contained highly substituted tetrahydroquinolines or cyclopentenes with three contiguous stereocenters bearing a quaternary carbon center in high yields with excellent diastereoselectivities and regioselectivities. Furthermore, synthetic utility of this strategy was further highlighted by gram-scale experiments and simple transformations of the products.

6.
Cell Mol Life Sci ; 79(2): 114, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35103851

RESUMEN

Sertoli cells are essential for spermatogenesis in the testicular seminiferous tubules by forming blood-testis barrier (BTB) and creating a unique microenvironment for spermatogenesis. Many lncRNAs have been reported to participate in spermatogenesis. However, the role of long noncoding RNAs (lncRNAs) in Sertoli cells has rarely been examined. Herein, we found that a high-fat diet (HFD) decreased sperm quality, impaired BTB integrity and resulted in accumulation of saturated fatty acids (SFAs), especially palmitic acid (PA), in mouse testes. PA decreased the expression of tight junction (TJ)-related proteins, increased permeability and decreased transepithelial electrical resistance (TER) in primary Sertoli cells and TM4 cells. Moreover, lncRNA Tug1 was found to be involved in PA-induced BTB disruption by RNA-seq. Tug1 depletion distinctly impaired the TJs of Sertoli cells and overexpression of Tug1 alleviated the disruption of BTB integrity induced by PA. Moreover, Ccl2 was found to be a downstream target of Tug1, and decreased TJ-related protein levels and TER and increased FITC-dextran permeability in vitro. Furthermore, the addition of Ccl2 damaged BTB integrity after overexpression of Tug1 in the presence of PA. Mechanistically, we found that Tug1 could directly bind to EZH2 and regulate H3K27me3 occupancy in the Ccl2 promoter region by RNA immunoprecipitation and chromatin immunoprecipitation assays. Our study revealed an important role of Tug1 in the BTB integrity of Sertoli cells and provided a new view of the role of lncRNAs in male infertility.


Asunto(s)
Barrera Hematotesticular/metabolismo , ARN Largo no Codificante/genética , Túbulos Seminíferos/irrigación sanguínea , Células de Sertoli/metabolismo , Espermatogénesis/genética , Uniones Estrechas/genética , Animales , Células Cultivadas , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Dieta Alta en Grasa , Impedancia Eléctrica , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Histonas/metabolismo , Infertilidad Masculina/genética , Masculino , Ratones , Ratones Endogámicos ICR , Obesidad/patología , Ácido Palmítico/análisis , Análisis de Semen , Espermatogénesis/fisiología
7.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(5): 843-851, 2023 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-37879912

RESUMEN

In order to fully explore the neural oscillatory coupling characteristics of patients with mild cognitive impairment (MCI), this paper analyzed and compared the strength of the coupling characteristics for 28 MCI patients and 21 normal subjects under six different-frequency combinations. The results showed that the difference in the global phase synchronization index of cross-frequency coupling under δ-θ rhythm combination was statistically significant in the MCI group compared with the normal control group ( P = 0.025, d = 0.398). To further validate this coupling feature, this paper proposed an optimized convolutional neural network model that incorporated a time-frequency data enhancement module and batch normalization layers to prevent overfitting while enhancing the robustness of the model. Based on this optimized model, with the phase locking value matrix of δ-θ rhythm combination as the single input feature, the diagnostic accuracy of MCI patients was (95.49 ± 4.15)%, sensitivity and specificity were (93.71 ± 7.21)% and (97.50 ± 5.34)%, respectively. The results showed that the characteristics of the phase locking value matrix under the combination of δ-θ rhythms can adequately reflect the cognitive status of MCI patients, which is helpful to assist the diagnosis of MCI.


Asunto(s)
Disfunción Cognitiva , Electroencefalografía , Humanos , Electroencefalografía/métodos , Disfunción Cognitiva/diagnóstico , Redes Neurales de la Computación , Sensibilidad y Especificidad
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(3): 450-457, 2023 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-37380383

RESUMEN

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.


Asunto(s)
Disfunción Cognitiva , Redes Neurales de la Computación , Humanos , Teorema de Bayes , Algoritmos , Encéfalo , Disfunción Cognitiva/diagnóstico
9.
Curr Issues Mol Biol ; 44(11): 5622-5637, 2022 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-36421665

RESUMEN

The NAC (NAM, ATAF1/2, and CUC2) gene family, one of the largest transcription factor families in plants, acts as positive or negative regulators in plant response and adaption to various environmental stresses, including cold stress. Multiple reports on the functional characterization of NAC genes in Arabidopsis thaliana and other plants are available. However, the function of the NAC genes in the typical woody mangrove (Kandelia obovata) remains poorly understood. Here, a comprehensive analysis of NAC genes in K. obovata was performed with a pluri-disciplinary approach including bioinformatic and molecular analyses. We retrieved a contracted NAC family with 68 genes from the K. obovata genome, which were unevenly distributed in the chromosomes and classified into ten classes. These KoNAC genes were differentially and preferentially expressed in different organs, among which, twelve up-regulated and one down-regulated KoNAC genes were identified. Several stress-related cis-regulatory elements, such as LTR (low-temperature response), STRE (stress response element), ABRE (abscisic acid response element), and WUN (wound-responsive element), were identified in the promoter regions of these 13 KoNAC genes. The expression patterns of five selected KoNAC genes (KoNAC6, KoNAC15, KoNAC20, KoNAC38, and KoNAC51) were confirmed by qRT-PCR under cold treatment. These results strongly implied the putative important roles of KoNAC genes in response to chilling and other stresses. Collectively, our findings provide valuable information for further investigations on the function of KoNAC genes.

10.
Cancer Sci ; 113(2): 796-801, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34812554

RESUMEN

Identifying molecular features is an essential component of the management and targeted therapy of brain metastases (BMs). The molecular features are different between primary lung cancers and BMs of lung cancer. Here we report the DNA and RNA mutational profiles of 43 pathological samples of BMs. In addition to previously reported mutational events associated with targeted therapy, PTPRZ1-MET, which was previously exclusively identified in glioma, was present in two cases of BMs of lung cancer. Furthermore, MET exon 14 skipping may be more common (6/37 cases) in BMs of lung cancer than the frequency previously reported in lung cancer. These findings highlight the clinical significance of targeted DNA plus RNA sequencing for BMs and suggest PTPRZ1-MET and MET exon 14 skipping as critical molecular events that may serve as targets of targeted therapy in BMs.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Fusión de Oncogenes , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/genética , Adulto , Anciano , Neoplasias Encefálicas/metabolismo , Exones , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/metabolismo
11.
EMBO J ; 37(20)2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30181118

RESUMEN

The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs in vitro Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Osteogénesis , Transducción de Señal , Proteasas Ubiquitina-Específicas/metabolismo , Animales , Proteína Morfogenética Ósea 2/genética , Regeneración Ósea/genética , Técnicas de Silenciamiento del Gen , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Noqueados , Osteoblastos/citología , Osteoblastos/metabolismo , Proteasas Ubiquitina-Específicas/genética
12.
Inorg Chem ; 61(17): 6451-6458, 2022 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-35438965

RESUMEN

Herein, we have successfully synthesized binary Ag2Se, composite Ag0:Ag2Se, and ternary Cu+:Ag2Se through an ambient aqueous-solution-based approach in a one-pot reaction at room temperature and atmospheric pressure without involving high-temperature heating, multiple-processes treatment, and organic solvents/surfactants. Effective controllability over phases and compositions/components are demonstrated with feasibility for large-scale production through an exquisite alteration in reaction parameters especially pH for enhancing and understanding thermoelectric properties. Thermoelectric ZT reaches 0.8-1.1 at near-room-temperature for n-type Ag2Se and Cu+ doping further improves to 0.9-1.2 over a temperature range of 300-393 K, which is the largest compared to that reported by wet chemistry methods. This improvement is related to the enhanced electrical conductivity and the suppressed thermal conductivity due to the incorporation of Cu+ into the lattice of Ag2Se at very low concentrations (x%Cu+:Ag2Se, x = 1.0, 1.5, and 2.0).

13.
Org Biomol Chem ; 20(34): 6923-6930, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-35979893

RESUMEN

An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.


Asunto(s)
Iminas , Ninhidrina , Carbonatos , Catálisis , Reacción de Cicloadición , Nitrilos , Pirazoles
14.
BMC Cardiovasc Disord ; 22(1): 422, 2022 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-36138345

RESUMEN

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA-miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA-mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.


Asunto(s)
Cardiomiopatía Hipertrófica , MicroARNs , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
15.
Environ Res ; 212(Pt C): 113405, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35525293

RESUMEN

Photocatalysis technology is used to remove the low concentration NO in recent years. However, the effect of this process is not very satisfactory. In this study, it was found that the prepositive NaOH solution could significantly improve the photocatalytic NO removal activity of g-C3N4. The apparent quantum yield of g-C3N4 in the NO removal process was increased 3.5 times by the prepositive NaOH solution. The reason is that there was a synergistic effect formed between the prepositive NaOH solution and the photocatalytic NO removal process. The prepositive NaOH solution not only could increase the humidity and pH value in the photocatalytic unit, but also could improve the adsorption ability of g-C3N4 for the H2O, NO, and O2. Moreover, the prepositive NaOH solution reduced the difficulty of the photogenerated carriers' transport and the ·OH generation. This study provided a new idea for the removal of low-concentration NOx.


Asunto(s)
Catálisis , Adsorción , Hidróxido de Sodio
16.
J Sep Sci ; 45(1): 338-346, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34416094

RESUMEN

In counter-current chromatography, the separation efficiency greatly depends on the partitioning ability of the separated substance between the stationary phase and the mobile phase. Partitioning ability is mainly represented by the parameter partition coefficient which is one of the important parameters to evaluate the separation effect of counter-current chromatography. The scope of the partition coefficient value mainly depends on the solvent system. A suitable solvent system election is, therefore, a critical role in the separation of counter-current chromatography. The existing solvent systems that are widely used are mainly two-phase solvent systems. It is difficult to decide on an appropriate solvent system for the separation of compounds with a wide polarity range, which promotes the development of the three-phase solvent system in counter-current chromatography. This review mainly described the origin, development history of three-phase solvent system, summarized the volume ratios and volume fractions of the upper, middle, and lower phases of nearly 50 three-phase solvent systems, their advantages, and disadvantages in counter-current chromatography. In addition, the challenges and future perspectives on three-phase solvent systems in counter-current chromatography also are discussed in this review.

17.
J Sep Sci ; 45(11): 1942-1951, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35332676

RESUMEN

The three-phase solvent system counter-current chromatography has been of great research interest, because it can separate compounds with a wide range of polarity. The solvent system of n-hexane/methyl tert-butyl ether/acetonitrile/water (5:5:7:5, v/v) was used for counter-current chromatographic comprehensive separation of olive leaves. The study adopted the normal elution mode. The middle phase and the lower phase (at a volume ratio of 7:3) were pumped into the column simultaneously, followed by eluting with the upper, middle, and lower phases in sequence. The retention rate of the stationary phase measured by the experiment was 73.5%. The upper phase was used to elute the nonpolar compounds, then the mobile phase was switched to the middle phase to elute the moderately hydrophobic compounds, finally, the polar compounds were eluted by the lower phase remaining in the chromatographic column. This method successfully separated eight compounds in one step within 270 min and five compounds were identified. The logP values of these five compounds were 7.44, 7.86, 4.16, -0.11, and 0.96, respectively, covering a wide range of polarities. The present study demonstrated that the three-phase solvent has a strong extraction capacity for ingredients from extremely hydrophilic compounds to extremely hydrophobic compounds.


Asunto(s)
Distribución en Contracorriente , Olea , Distribución en Contracorriente/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Hojas de la Planta , Solventes/química
18.
Neural Plast ; 2022: 8511066, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860309

RESUMEN

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-ß, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.


Asunto(s)
Epilepsia del Lóbulo Temporal , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Cromatografía Liquida , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/inducido químicamente , Hipocampo/metabolismo , Plasticidad Neuronal , Pilocarpina , Proteómica , Ratas , Espectrometría de Masas en Tándem
19.
Rare Metals ; 41(12): 4138-4148, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36157375

RESUMEN

The daily life of people in the intelligent age is inseparable from electronic device, and a number of bacteria on touch screens are increasingly threatening the health of users. Herein, a photocatalytic TiO2/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction. Ultraviolet-visible (UV-Vis) spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO2. The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO2/Ag film against S. aureus and E. coli was 98.2% and 98.6%, under visible light irradiation for 5 min. The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO2 reduced the bandgap of TiO2 from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO2 and Ag. Thus, TiO2/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens. More importantly, the TiO2/Ag film had great biocompatibility with/without light irradiation. The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.

20.
Neuroimage ; 226: 117555, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33189933

RESUMEN

The mechanistic and neural bases of why green environments drive positive mental health outcomes remain poorly understood. We show that viewing green urban landscapes that vary in terms of green-space density elicits corresponding changes in the activity of the human ventral posterior cingulate cortex that is correlated to behavioural stress-related responses. We further show that cingulate responses are engaged early in the processing cascade, influencing attentional and executive regions in a predominantly feedforward manner. Our data suggest a key role for this region in regulating (nature) dose-dependent changes in stress responses, potentially through its extensive connections to the prefrontal and hippocampal regions which in turn project towards the neuroendocrine system. As the posterior cingulate cortex is implicated in a variety of neurological diseases and disorders, these findings raise a therapeutic potential for natural environmental exposure, highlighting green-cover as a modifiable element that links to changes in limbic responses, and has health consequences for practitioners and city-planners alike.


Asunto(s)
Giro del Cíngulo/diagnóstico por imagen , Salud Mental , Parques Recreativos , Atención/fisiología , Emociones/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Adulto Joven
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