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1.
FASEB J ; 37(2): e22724, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36583687

RESUMEN

Mitosis entails global and dramatic alterations, such as higher-order chromatin organization disruption, concomitant with global transcription downregulation. Cells reliably re-establishing gene expression patterns upon mitotic exit and maintaining cellular identities remain poorly understood. Previous studies indicated that certain transcription factors (TFs) remain associated with individual loci during mitosis and serve as mitotic bookmarkers. However, it is unclear which regulatory factors remain bound to the compacted mitotic chromosomes. We developed formaldehyde-assisted isolation of regulatory elements-coupled mass spectrometry (FAIRE-MS) that combines FAIRE-based open chromatin-associated protein pull-down and mass spectrometry (MS) to quantify the open chromatin-associated proteome during the interphase and mitosis. We identified 189 interphase and mitosis maintained (IM) regulatory factors using FAIRE-MS and found intrinsically disordered proteins and regions (IDP(R)s) are highly enriched, which plays a crucial role in liquid-liquid phase separation (LLPS) and chromatin organization during the cell cycle. Notably, in these IDP(R)s, we identified mitotic bookmarkers, such as CEBPB, HMGB1, and TFAP2A, and several factors, including MAX, HMGB3, hnRNP A2/B1, FUS, hnRNP D, and TIAL1, which are at least partially bound to the mitotic chromosome. Furthermore, it will be essential to study whether these IDP(R)s through LLPS helps cells transit from mitosis to the G1 phase during the cell cycle.


Asunto(s)
Cromatina , Proteoma , Proteoma/genética , Cromatina/genética , Cromosomas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Mitosis , Espectrometría de Masas
2.
Biomacromolecules ; 25(6): 3784-3794, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38743836

RESUMEN

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.


Asunto(s)
Regeneración Ósea , Células Madre Mesenquimatosas , Osteogénesis , Poliésteres , Ingeniería de Tejidos , Andamios del Tejido , Animales , Andamios del Tejido/química , Ratas , Regeneración Ósea/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Ingeniería de Tejidos/métodos , Poliésteres/química , Diferenciación Celular , Ratas Sprague-Dawley , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Células Cultivadas , Proliferación Celular , Cráneo/lesiones , Cráneo/patología , Durapatita/química , Durapatita/farmacología
3.
Nano Lett ; 23(14): 6378-6385, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37418477

RESUMEN

Unidirectional magnetoresistance (UMR) has been intensively studied in ferromagnetic systems, which is mainly induced by spin-dependent and spin-flip electron scattering. Yet, UMR in antiferromagnetic (AFM) systems has not been fully understood to date. In this work, we reported UMR in a YFeO3/Pt heterostructure where YFeO3 is a typical AFM insulator. Magnetic-field dependence and temperature dependence of transport measurements indicate that magnon dynamics and interfacial Rashba splitting are two individual origins for AFM UMR, which is consistent with the UMR theory in ferromagnetic systems. We further established a comprehensive theoretical model that incorporates micromagnetic simulation, density functional theory calculation, and the tight-binding model, which explain the observed AFM UMR phenomenon well. Our work sheds light on the intrinsic transport property of the AFM system and may facilitate the development of AFM spintronic devices.

4.
Nano Lett ; 23(18): 8816-8826, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37459451

RESUMEN

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.


Asunto(s)
Ácidos Nucleicos , Sarcopenia , Humanos , Anciano , Ratones , Animales , Sarcopenia/tratamiento farmacológico , Sarcopenia/patología , Ácidos Nucleicos/uso terapéutico , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/patología , Apoptosis , Mitocondrias/patología
5.
Biochem Cell Biol ; 101(3): 235-245, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36786377

RESUMEN

In the process of orthodontic tooth movement (OTM), periodontal ligament fibroblasts (PDLFs) must undergo osteogenic differentiation. OTM increased the expression of Zinc finger and BTB domain-containing 16 (ZBTB16), which is implicated in osteogenic differentiation. Our goal was to investigate the mechanism of PDLF osteogenic differentiation mediated by ZBTB16. The OTM rat model was established, and PDLFs were isolated and exposed to mechanical force. Hematoxylin-eosin staining, Alizarin Red staining, immunofluorescence, and immunohistochemistry were carried out. The alkaline phosphatase (ALP) activity was measured. Dual-luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted. In OTM models, ZBTB16 was significantly expressed. Additionally, there was an uneven distribution of PDLFs in the OTM group, as well as an increase in fibroblasts and inflammatory infiltration. ZBTB16 interference hindered PDLF osteogenic differentiation and decreased Wnt and ß-catenin levels. Meanwhile, ZBTB16 activated the Wnt/ß-catenin pathway. ZBTB16 also enhanced the expression of the osteogenic molecules osterix, osteocalcin (OCN), osteopontin (OPN), and bone sialo protein (BSP) at mRNA and protein levels. The interactions between Wnt1 and ZBTB16, as well as GCN5 and ZBTB16, were also verified. The adeno-associated virus-shZBTB16 injection also proved to inhibit osteogenic differentiation and reduce tooth movement distance in in vivo tests. ZBTB16 was up-regulated in OTM. Through acetylation modification of ZBTB16, GCN5 regulated the Wnt/ß-catenin signaling pathway and further mediated PDLF osteogenic differentiation.


Asunto(s)
Osteogénesis , beta Catenina , Ratas , Animales , Osteogénesis/genética , beta Catenina/metabolismo , Acetilación , Técnicas de Movimiento Dental , Ligamento Periodontal , Vía de Señalización Wnt/genética , Diferenciación Celular , Células Cultivadas , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Histona Acetiltransferasas/metabolismo
6.
Cell Mol Biol Lett ; 28(1): 74, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37723445

RESUMEN

BACKGROUND: Cardiomyocyte death induced by autophagy inhibition is an important cause of cardiac dysfunction. In-depth exploration of its mechanism may help to improve cardiac dysfunction. In our previous study, we found that ß1-adrenergic receptor autoantibodies (ß1-AAs) induced a decrease in myocardial autophagy and caused cardiomyocyte death, thus resulting in cardiac dysfunction. Through tandem mass tag (TMT)-based quantitative proteomics, autophagy-related S100a9 protein was found to be significantly upregulated in the myocardial tissue of actively immunized mice. However, whether S100a9 affects the cardiac function in the presence of ß1-AAs through autophagy and the specific mechanism are currently unclear. METHODS: In this study, the active immunity method was used to establish a ß1-AA-induced mouse cardiac dysfunction model, and RT-PCR and western blot were used to detect changes in gene and protein expression in cardiomyocytes. We used siRNA to knockdown S100a9 in cardiomyocytes. An autophagy PCR array was performed to screen differentially expressed autophagy-related genes in cells transfected with S100a9 siRNA and negative control siRNA. Cytoplasmic nuclear separation, co-immunoprecipitation (Co-IP), and immunofluorescence were used to detect the binding of S100a9 and hypoxia inducible factor-1α (HIF-1α). Finally, AAV9-S100a9-RNAi was injected into mice via the tail vein to knockdown S100a9 in cardiomyocytes. Cardiac function was detected via ultrasonography. RESULTS: The results showed that ß1-AAs induced S100a9 expression. The PCR array indicated that Atg9a changed significantly in S100a9siRNA cells and that ß1-AAs increased the binding of S100a9 and HIF-1α in cytoplasm. Knockdown of S100a9 significantly improved autophagy levels and cardiac dysfunction. CONCLUSION: Our research showed that ß1-AAs increased S100a9 expression in cardiomyocytes and that S100a9 interacted with HIF-1α, which prevented HIF-1α from entering the nucleus normally, thus inhibiting the transcription of Atg9a. This resulted in autophagy inhibition and cardiac dysfunction.


Asunto(s)
Calgranulina B , Miocitos Cardíacos , Animales , Ratones , Autoanticuerpos , Autofagia , Modelos Animales de Enfermedad , Miocardio
7.
Anim Biotechnol ; 34(4): 1524-1531, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35209806

RESUMEN

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3) belongs to the serine protease inhibitor family A subtype, and contains 8 genes from SERPINA3-1 to SERPINA3-8. Although the regulatory effects of these 8 genes have been revealed one by one in recent years, the related effects of SERPINA3-1 gene on cattle growth is still unclear. This study used quantitative Real time PCR (qPCR) to detect the type of copy number variation (CNV) of SERPINA3-1 gene in a total of 542 Chinese cattle, and expression of SERPINA3-1 gene in different tissues of Qinchuan cattles (adult) on mRNA level. Then association analysis was conducted between the detection results and cattle growth traits. The results showed that the Duplication type in SERPINA3-1 gene performed better on the growth traits and the CNV was significantly correlated with multiple growth traits (p < 0.05). In addition, SERPINA3-1 gene has different expression conditions in different tissues, results showed that SERPINA3-1 gene has a low expression in muscle. In conclusion, we speculate that the SERPINA3-1 gene can be used as a molecular marker and the result of this study could be a basic material for candidate functional genes for beef cattle growth and development.


In order to detect the gene expression diversification of the SERPINA3-1 gene, blood samples were collected from five Chinese cattle breeds, we detected related signal and made an associated analyze with cattle growth traits. We determined the copy number variation distribution of the SERPINA3-1 gene in cattle populations and found that the SERPINA3-1 gene has a certain promoting effect on the growth and development of Chinese cattle. For example, Pinan cattle with Duplication type copy number have a better performance on growth traits. This study has enriched the candidate genes of Chinese cattle molecular breeding and provided basic data for Chinese cattle breeding.


Asunto(s)
Variaciones en el Número de Copia de ADN , Animales , Bovinos/genética , Variaciones en el Número de Copia de ADN/genética , Fenotipo , Peso Corporal/genética
8.
Arch Pharm (Weinheim) ; 356(6): e2200592, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37021586

RESUMEN

The "magic methyl effect" strategy was used to design a series of 5-alkyl-2-pyrazol-oxazolidin-4-one derivatives as novel hepatitis B virus (HBV) capsid assembly modulators. Most of these compounds exhibited potent HBV inhibitory activities with low cytotoxicities in HepG2.2.15 cells. The most promising compounds 9d and 10b had single-digit nanomolar IC50 values with a high selectivity index. Compared with the lead compound (3.0%), they caused 15% and 18% decreases in HBe antigen secretion at 1.0 µM, respectively. In addition, compounds 9d and 10b possessed good pharmacokinetic profiles with oral bioavailability values of 56.1% and 48.9%, respectively. These results indicated that the two compounds were potential therapeutic agents for HBV infection.


Asunto(s)
Cápside , Virus de la Hepatitis B , Ensamble de Virus , Antivirales/farmacología , Relación Estructura-Actividad , Proteínas de la Cápside/farmacología , Replicación Viral
9.
Molecules ; 28(7)2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37049761

RESUMEN

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm-2, 97.22 ± 1.39% at 720 g a.i.·hm-2, 100.00% at 900.00 g a.i.·hm-2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm-2), and pomelo peel oil (100.00% at 900 g a.i.·hm-2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.


Asunto(s)
Citrus , Insecticidas , Aceites Volátiles , Rutaceae , Thysanoptera , Zanthoxylum , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Insecticidas/farmacología , Aceites de Plantas/farmacología , Aceites de Plantas/química , Citrus/química , Zanthoxylum/química
10.
Acta Chir Belg ; 123(4): 448-453, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35135434

RESUMEN

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by a predisposition to the development of multiple neoplasms. Gastric-type mucinous adenocarcinoma (GAS), a new variant of carcinoma of the cervix according to 2014 WHO classification, is less common compared with squamous cell carcinoma, is more aggressive and has a lower 5-year survival rate compared with the usual-type endocervical adenocarcinoma, and is also unrelated to human papillomavirus (HPV) infection. CASE SUMMARY: We herein present the case of a 32-year-old patient with PJS who was diagnosed with GAS of the cervix. The patient was not sexually active and had been diagnosed with PJS at 2 years of age. A tumor ∼6 cm was found on the cervix and was diagnosed as GAS of the cervix of clinical-stage IB3. The patient was treated with intra-arterial chemotherapy for one course, followed by radical surgery and then systematic chemotherapy. CONCLUSION: The present case highlights the need for more thorough cancer screening for patients with PJS, as this disorder is rare and is associated with a high risk of malignancies. Young patients with PJS, including those who are not sexually active, who present with watery vaginal discharge or bleeding should be screened for cervical carcinoma, even if the cytological results or HPV tests are negative.


Asunto(s)
Adenocarcinoma Mucinoso , Infecciones por Papillomavirus , Síndrome de Peutz-Jeghers , Neoplasias Gástricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Cuello del Útero/patología , Síndrome de Peutz-Jeghers/complicaciones , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/cirugía , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma Mucinoso/complicaciones , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirugía , Neoplasias Gástricas/patología
11.
BMC Genomics ; 23(1): 483, 2022 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-35780101

RESUMEN

BACKGROUND: Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. METHODS: In our study, we constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. RESULTS: Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. CONCLUSION: These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Proliferación Celular/genética , Ratas , Transactivadores/genética , Transactivadores/metabolismo
12.
BMC Cancer ; 22(1): 1140, 2022 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335306

RESUMEN

BACKGROUND: Our previous study reported that recombinant human epidermal growth factor (rhEGF)-triggered EGFR internalization promoted radioresistance. Here, we aimed to evaluate the effect of rhEGF on the skin protection of rectal and anal cancer patients receiving radiotherapy. METHODS: One hundred and ninety-three rectal and anal cancer patients who received radiotherapy were prospectively enrolled from January 2019 to December 2020. To perform self-controlled study, the left and right pelvic skin area (separated by midline) were randomly assigned to the rhEGF and control side. The association between radiation dermatitis and factors including rhEGF, the dose of radiotherapy and tumor distance from anal edge were analyzed. RESULTS: Among 193 enrolled patients, 41 patients (21.2%) did not develop radiation dermatitis, and 152 patients (78.8%) suffered radiation dermatitis on at least one side of pelvic skin at the end of radiotherapy. For the effect on radiation dermatitis grade, rhEGF had improved effect on 6 (4.0%) patients, detrimental effect on 2 (1.3%) patients, and no effect on 144 (94.7%) patients. Whereas for the effect on radiation dermatitis area, rhEGF showed improved effect on the radiation dermatitis area of 46 (30.2%) patients, detrimental effect on 15 (9.9%) patients, and no effect on 91 (59.9%) patients. The radiation dermatitis area of rhEGF side was significantly smaller than that of control side (P = 0.0007). CONCLUSIONS: rhEGF is a skin protective reagent for rectal and anal cancer patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR1900020842; Date of registration: 20/01/2019.


Asunto(s)
Neoplasias del Ano , Radiodermatitis , Humanos , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/radioterapia , Factor de Crecimiento Epidérmico/uso terapéutico , Radiodermatitis/tratamiento farmacológico , Radiodermatitis/etiología , Proyectos de Investigación
13.
Glycoconj J ; 39(6): 759-772, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36342595

RESUMEN

In this study, a water-soluble polysaccharide from Eucommia folium was extracted by hot water and purified using Sephadex G-200 gel columns. The results showed that the purified fraction (EFP) has a molecular weight of 9.98 × 105 Da and consisted of rhamnose, arabinose, galactose, glucose, mannose, xylose, galacturonic acid, and glucuronic acid (molar ratio: 0.226: 1.739: 2.183: 1: 0.155: 0.321: 0.358: 0.047). The combination of infrared spectroscopy and NMR analysis proved that EFP is an acidic polysaccharide whose main chain consists of α-L-Araf-(1 → , → 3,5)-α-Araf-(1 → , → 3)-ß-Galp-(1 → , → 3,6)-ß-Glcp-(1 → , → 2)-α-D-Manp-(1 → , → 4)-α-GalpA-(1 → , → 2,4)-α-Rhap-(1 → . In addition, the in vivo antitumoral activity of EFP was studied using a H22 tumor-bearing mice model. EFP effectively inhibited tumor growth in mice following intragastric administration. By Combining with the results of the apoptosis assay and JC-1 staining analysis, we confirmed that EFP induces apoptosis through the mitochondrial pathway. Furthermore, cell cycle analysis demonstrated that EFP blocks the cell cycle at S phase.


Asunto(s)
Polisacáridos , Agua , Ratones , Animales , Polisacáridos/química , Galactosa , Ramnosa , Peso Molecular
14.
PLoS Comput Biol ; 17(5): e1008987, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34048425

RESUMEN

Modification of the Per2 clock gene in mPer2Luc reporter mice significantly alters circadian function. Behavioral period in constant dark is lengthened, and dissociates into two distinct components in constant light. Rhythms exhibit increased bimodality, enhanced phase resetting to light pulses, and altered entrainment to scheduled feeding. Mechanistic mathematical modelling predicts that enhanced protein interactions with the modified mPER2 C-terminus, combined with differential clock regulation among SCN subregions, can account for effects on circadian behavior via increased Per2 transcript and protein stability. PER2::LUC produces greater suppression of CLOCK:BMAL1 E-box activity than PER2. mPer2Luc carries a 72 bp deletion in exon 23 of Per2, and retains a neomycin resistance cassette that affects rhythm amplitude but not period. The results show that mPer2Luc acts as a circadian clock mutation illustrating a need for detailed assessment of potential impacts of c-terminal tags in genetically modified animal models.


Asunto(s)
Ritmo Circadiano , Luciferasas/genética , Proteínas Circadianas Period/genética , Animales , Conducta Animal , Conducta Alimentaria , Locomoción , Ratones , Ratones Endogámicos C57BL , Mutación
15.
Anesth Analg ; 135(4): 865-876, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35819160

RESUMEN

BACKGROUND: The number of patients with diabetic neuropathic pain (DNP) continues to increase, but available treatments are limited. This study aimed to examine the influence of reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NOD-like receptor protein 3 (NLRP3)- N -methyl-D-aspartic acid receptor 2B (NR2B) pathway on type 2 DNP. METHODS: Male Sprague-Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks. Then, rats were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg) to induce type 2 diabetes mellitus in rats. Diabetic rats with <85% of their basic levels in mechanical withdrawal threshold and thermal withdrawal latency were classified as DNP rats on day 14 after STZ injection. DNP rats were treated with ROS scavenger N-tert-Butyl-α-phenylnitrone (PBN, 100 mg·kg -1 ·d -1 ) or TXNIP small interfering ribonucleic acid (10 µg/d) once daily for 14 days. The level of ROS, protein levels of NLRP3, TXNIP, cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1ß (IL-1ß), NR2B phosphorylation at Tyr1472 (p-NR2B), total NR2B (t-NR2B), and distribution of NLRP3 in the spinal cord were examined. In vitro experiments, BV2 cells and PC12 cells were individually cultured and cocultured in a high-glucose environment (35 mmol/L D-glucose). The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, and IL-1ß in BV2 cells, and p-NR2B, t-NR2B in PC12 cells were detected. The level of ROS was detected by the flow cytometry approach. The protein levels were detected by the Western blot technique. The location of NLRP3 was observed by immunofluorescent staining. The interaction between TXNIP and NLRP3 was detected by coimmunoprecipitation assay. RESULTS: The level of spinal ROS increased in DNP rats. The mechanical allodynia and thermal hyperalgesia of DNP rats were alleviated after systemic administration of PBN. This administration decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1ß, and p-NR2B and the coupling of TXNIP to NLRP3 in spinal cords of DNP rats. Furthermore, knockdown of spinal TXNIP alleviated nociceptive hypersensitivity and decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1ß, and p-NR2B in DNP rats. The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, IL-1ß, the coupling of TXNIP to NLRP3, and the IL-1ß secretion increased in BV2 cells, and the protein expression of p-NR2B increased in cocultured PC12 cells in a high-glucose environment. All of these in vitro effects were significantly blocked after treatment of PBN. CONCLUSIONS: Our findings suggest that spinal ROS can contribute to type 2 DNP through TXNIP-NLRP3-NR2B pathway.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuralgia , Animales , Ácido Aspártico , Caspasas , Proteínas de Ciclo Celular , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Glucosa , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Péptido Hidrolasas , ARN , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de Aminoácidos , Estreptozocina , Tiorredoxinas
16.
Acta Pharmacol Sin ; 42(5): 735-743, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32770172

RESUMEN

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.


Asunto(s)
Berberina/uso terapéutico , Hiperinsulinismo/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina/fisiología , Animales , Línea Celular , Ciclofilinas/metabolismo , Emulsiones , Humanos , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/metabolismo , Masculino , Ratones , Células Musculares/efectos de los fármacos , Células Musculares/metabolismo , Fosfolípidos , Ratas Sprague-Dawley , Aceite de Soja
17.
Neurosurg Rev ; 44(3): 1457-1469, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32535873

RESUMEN

Both posterior decompression and fusion (PDF) and laminoplasty (LAMP) have been used to treat cervical myelopathy due to multilevel ossification of posterior longitudinal ligament (OPLL). However, considerable controversy exists over the choice of the two surgical strategies. Thus, the aim of this study is to compare clinical outcomes of PDF and LAMP for treatment of cervical myelopathy due to multilevel OPLL. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials database to identify relevant clinical studies compared with clinical outcomes of PDF and LAMP for cervical OPLL. The primary outcomes including Japanese Orthopaedic Association (JOA) score and recovery rate of JOA were evaluated, and the secondary outcomes involving visual analogue scale (VAS), cervical curvature, OPLL progression rate, complication rate, reoperation rate and surgical trauma were also evaluated using Stata software. A total of nine studies were included in the current study, involving 324 patients. The current study suggests that compared with LAMP, PDF achieves a lower OPLL progression rate, better postoperative cervical curvature and similar neurological improvement in the treatment of multilevel cervical OPLL. However, PDF has a higher complication rate, more surgical trauma and higher postoperative VAS than LAMP.


Asunto(s)
Vértebras Cervicales/cirugía , Descompresión Quirúrgica/tendencias , Laminoplastia/tendencias , Osificación del Ligamento Longitudinal Posterior/cirugía , Complicaciones Posoperatorias/etiología , Fusión Vertebral/tendencias , Vértebras Cervicales/patología , Descompresión Quirúrgica/efectos adversos , Humanos , Laminoplastia/efectos adversos , Osificación del Ligamento Longitudinal Posterior/diagnóstico , Dimensión del Dolor/métodos , Dimensión del Dolor/tendencias , Complicaciones Posoperatorias/diagnóstico , Reoperación/tendencias , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Resultado del Tratamiento
18.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3712-3721, 2021 Jul.
Artículo en Zh | MEDLINE | ID: mdl-34402296

RESUMEN

This study aimed to analyze the methodological quality of systematic reviews of Shuxuening Injection and evaluate the efficacy and adverse reactions of Shuxuening Injection in the treatment of different diseases,in order to provide supportive evidence for clinical practice. Three Chinese databases and three English databases were retrieved to identify systematic reviews and Meta-analysis on the efficacy and safety of Shuxuening Injection in the treatment of diseases. The AMSTAR 2( a measurement tool to assess systematic reviews 2) tool was used to evaluate the methodological quality of the included systematic reviews,and tables were created to present the results of Meta-analyses. Twenty-four systematic reviews were included,all with very low methodological quality. Among the 16 AMSTAR-2 items,only 5 items had a compliance rate greater than 60. 0%,and 8 items had a compliance rate less than 50. 0%. For patients with cerebral infarction,Shuxuening Injection combined with conventional treatment was more effective than conventional treatment alone in terms of clinical efficiency and neurological deficit improvement. For patients with angina pectoris,Shuxuening Injection was superior to Danshen/Compound Danshen Injection in terms of the total effective rate of angina pectoris and total effective rate of ECG. The efficacy of Shuxuening Injection combined with conventional treatment is significantly better than conventional treatment.Shuxuening Injection( alone or combined with conventional treatments) was better than conventional treatments for cerebral hemorrhage,ischemic cerebrovascular disease,chronic pulmonary heart disease,vertigo and sudden deafness. Shuxuening Injection had better efficacy and lower incidence of adverse reactions,but the methodological quality of included systematic reviews was low. The results of this study still need to be verified by high-quality systematic reviews.


Asunto(s)
Salvia miltiorrhiza , Angina de Pecho/tratamiento farmacológico , Medicamentos Herbarios Chinos , Humanos , Inyecciones , Revisiones Sistemáticas como Asunto
19.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3998-4007, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34472277

RESUMEN

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.


Asunto(s)
Medicamentos Herbarios Chinos , Enfermedad Cardiopulmonar , Combinación de Medicamentos , Humanos , Revisiones Sistemáticas como Asunto
20.
Analyst ; 145(13): 4432-4435, 2020 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-32441734

RESUMEN

Highly efficient enrichment of target glycopeptides plays a crucial role in glycoproteome research. Owing to their large surface area and excellent hydrophilicity, 2-D Hf-BTB nanosheets showed effective and selective enrichment of 78 glycopeptides derived from 29 glycoproteins with 90 N-glycosylation sites from just 2 µL of human serum.

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