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The ovary is an important organ for women to maintain reproductive and endocrine functions. Ovarian aging can lead to female reproductive aging, which is a key factor causing rapid aging of the female body. Umbilical cord-derived MSCs (UC-MSCs) play a therapeutic role in various degenerative diseases. Dehydroepiandrosterone (DHEA) is widely used in the treatment of reversing oocyte quality. However, it is unclear whether UC-MSCs combined with DHEA supplementation can improve ovarian senescence in naturally aging mice. To address this question, we studied the influence of the combination of human UC-MSCs (hUC-MSCs) and DHEA on ovarian morphology and function in naturally aging mice. The results showed a significant augmentation in the number of primary follicles, as well as a significant upregulation of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) hormone levels, and a significant increase in survival rate in naturally aging mice treated by hUC-MSCs and DHEA. Moreover, the combination of hUC-MSCs and DHEA significantly reduced the reactive oxygen species (ROS) level and downregulated the expression levels of proinflammatory factors IL-6, IL-18, and TNF-α. Furthermore, the PI3K/AKT/mTOR pathway was inhibited. Conclusively, the combination therapy of hUC-MSC + DHEA contributed to restore ovarian function in aging mice and extend their lifespan by restoring hormone levels and inhibiting inflammatory factors.
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Dandelion (Taraxacum genus), a perennial herb belonging to the Asteraceae family is widely distributed in hillside grasslands, roadsides, fields, and river beaches in middle and low-altitude areas. It has a long history of traditional Chinese medicine usage as a heat-clearing and detoxifying agent, often consumed as tea or vegetable. Multiple pharmacological studies have demonstrated the antiviral, antibacterial, anti-inflammatory, immune-regulating, antioxidant, anti-tumor, and other effects of the Taraxacum genus. Bioactive compounds associated with these effects include triterpenes and their saponins, phenolic acids, sterols and their glycosides, flavonoids, organic acids, volatile oils, and saccharides.
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BACKGROUND: The efficient and timely determination of polymethoxylated flavones (PMFs, primarily nobiletin and tangeretin) and flavanone glycosides (primarily hesperidin) in Citri Reticulatae Pericarpium (CRP) is of paramount importance for the production of CRP and the evaluation of its efficacy. Conventional analytical methods including chromatography-based approaches commonly provide high sensitivity and selectivity, but require bulky equipment and complicated procedures performed by professional technicians and are thus inconvenient in practical applications. Therefore, there is a clear need for portable and miniaturized sensing platforms that can rapidly and simultaneously detect PMFs and hesperidin in CRP product. RESULTS: A state-of-the-art three-dimensional porous graphene electrode was first fabricated by direct laser scribing of a poly(ether-ether-ketone) (PEEK) film for electrocatalysis of nobiletin, tangeretin and hesperidin. Kinetic analysis was conducted to investigate the reaction mechanisms of these three flavonoids at such prepared PEEK-laser induced graphene (PEEK-LIG) electrodes. Since the as-prepared PEEK-LIG electrodes exhibited high electrocatalytic efficiency towards these three flavonoids, a portable electrochemical sensing platform assembled with a smartphone, a miniatured electrochemical workstation, and an integrated PEEK-LIG microchip was developed. Consequently, the developed portable electrochemical sensing platforms exhibited great sensitivity and low detection limits for both PMFs and hesperidin. More importantly, tests conducted on real CRP extract samples demonstrated that the developed portable electrochemical sensing platform exhibited high validity, high reliability, as well as excellent reproducibility. SIGNIFICANCE: This is the inaugural report on the portable and simultaneous determination of PMFs and hesperidin in the pericarp of Citrus Reticulata, which may be utilized for differentiating CRP products. Furthermore, the portable and powerful electrochemical sensing platforms developed could also potentially be applied for a wide range of analytes, thanks to their simple and rapid fabrication and determination processes.
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Citrus , Técnicas Eletroquímicas , Eletrodos , Flavonoides , Smartphone , Citrus/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Flavonoides/análise , Grafite/química , Limite de Detecção , Hesperidina/análiseRESUMO
Two-dimensional covalent organic frameworks (2D-COFs) have recently emerged as fascinating scaffolds for solar-to-chemical energy conversion because of their customizable structures and functionalities. Herein, two tris(triazolo)triazine-based COF materials (namely COF-JLU51 and COF-JLU52) featuring large surface area, high crystallinity, excellent stability and photoelectric properties were designed and constructed for the first time. Remarkably, COF-JLU51 gave an outstanding H2O2 production rate of over 4200â µmol g-1 h-1 with excellent reusability in pure water and O2 under one standard sun light, that higher than its isomorphic COF-JLU52 and most of the reported metal-free materials, owing to its superior generation, separation and transport of photogenerated carriers. Experimental and theoretical researches prove that the photocatalytic process undergoes a combination of indirect 2e- O2 reduction reaction (ORR) and 4e- H2O oxidation reaction (WOR). Specifically, an ultrahigh yield of 7624.7â µmol g-1 h-1 with apparent quantum yield of 18.2 % for COF-JLU52 was achieved in a 1 : 1 ratio of benzyl alcohol and water system. This finding contributes novel, nitrogen-rich and high-quality tris(triazolo)triazine-based COF materials, and also designate their bright future in photocatalytic solar transformations.
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BACKGROUND: Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. METHODS: The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. CONCLUSIONS: Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.
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Procedimentos Endovasculares , Insuficiência Vertebrobasilar , Humanos , Procedimentos Endovasculares/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/complicações , Resultado do Tratamento , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , China/epidemiologiaRESUMO
OBJECTIVE: Autologous iliac bone is commonly used as a bone graft material to achieve solid fusion in craniocervical junction (CVJ) surgery. However, the developing iliac bone of children is less than ideal as a bone graft material. The matured rib bone of children presents a potential substitute material for iliac bone. The aim of this study was to evaluate the efficacy of autologous rib grafts for craniocervical junction surgery in children. METHODS: The outcomes of 10 children with abnormalities of the craniocervical junction who underwent craniocervical junction surgery between January 2020 and December 2022 were retrospectively reviewed. All patients underwent posterior fusion and internal fixation surgery with autologous rib grafts. Pre- and post-operative images were obtained and clinical follow-ups were conducted to evaluate neurological function, pain level, donor site complications, and bone fusion rates. RESULTS: All surgeries were successful. During the 8- to 24-month follow-up period, all patients achieved satisfactory clinical results. Computed tomography at 3-6 months confirmed successful bone fusion and regeneration of the rib defect in all patients with no neurological or donor site complications. CONCLUSION: Autologous rib bone is a safe and effective material for bone grafting in craniocervical junction fusion surgery for children that can reduce the risks of donor site complications and increase the amount of bone graft, thereby achieving a higher bone fusion rate.
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Transplante Ósseo , Costelas , Fusão Vertebral , Transplante Autólogo , Humanos , Criança , Masculino , Feminino , Estudos Retrospectivos , Fusão Vertebral/métodos , Transplante Ósseo/métodos , Costelas/transplante , Costelas/cirurgia , Transplante Autólogo/métodos , Resultado do Tratamento , Pré-Escolar , Adolescente , Articulação Atlantoaxial/cirurgia , Articulação Atlantoaxial/diagnóstico por imagem , Seguimentos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Articulação Atlantoccipital/cirurgia , Articulação Atlantoccipital/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: It is still unknown whether unsaturated fatty acids (UFA) have the same effect on preventing cognitive impairment in chronic kidney disease (CKD) patients as in healthy people. OBJECTIVE: To investigate the protective effect of dietary UFA intake and proportion on cognitive impairment in patients with CKD. METHODS: We extracted data from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) on participants with a previous diagnosis of CKD and at least one complete cognitive assessment (Consortium to Establish a Registry for Alzheimer's Disease test, Animal Fluency Test and Digit Symbol Substitution Test). We used the lower quartile of the total scores of these three tests as the cut-off point, and divided the participants into two groups of normal cognitive performance and low cognitive performance to extract participants' intake of various UFA from the NHANES dietary module.
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With the postponement of the reproductive age of women, the difficulty of embryo implantation caused by uterine aging has become a key factor restricting fertility. However, there are few studies on protective interventions for naturally aging uteri. Although many factors cause uterine aging, such as oxidative stress (OS), inflammation, and fibrosis, their impact on uterine function manifests as reduced endometrial receptivity. This study aimed to use a combination of human umbilical cord mesenchymal stem cells (hUC-MSCs) and dehydroepiandrosterone (DHEA) to delay uterine aging. The results showed that the combined treatment of hUC-MSCs + DHEA increased the number of uterine glandular bodies and the thickness of the endometrium while inhibiting the senescence of endometrial epithelial cells. This combined treatment alleviates the expression of OS (reactive oxygen species, superoxide dismutase, and GSH-PX) and proinflammatory factors (interleukin [IL]-1, IL6, IL-18, and tumor necrosis factor-α) in the uterus, delaying the aging process. The combined treatment of hUC-MSCs + DHEA alleviated the abnormal hormone response of the endometrium, inhibited excessive accumulation and fibrosis of uterine collagen, and upregulated uterine estrogen and progesterone receptors through the PI3K/AKT/mTOR pathway. This study suggests that uterine aging can be delayed through hUC-MSCs + DHEA combination therapy, providing a new treatment method for uterine aging.
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Envelhecimento , Desidroepiandrosterona , Inflamação , Células-Tronco Mesenquimais , Cordão Umbilical , Útero , Feminino , Humanos , Desidroepiandrosterona/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Animais , Camundongos , Inflamação/patologia , Inflamação/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismo , Útero/patologia , Estresse Oxidativo/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais/métodos , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/citologia , Endométrio/patologia , Senescência Celular/efeitos dos fármacos , Fibrose , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To develop posterior reduction forceps for atlantoaxial dislocation and evaluate the preliminary clinical application of this forceps in assisting simple posterior screw-rod system reduction and fixation in the treatment of irreducible atlantoaxial dislocation. METHODS: Based on the posterior atlantoaxial screw-rod system, posterior reduction forceps was developed to assist simple posterior screw-rod system for the treatment of irreducible atlantoaxial dislocation. From January 2021 to October 2022, 10 cases with irreducible atlantoaxial dislocation were treated with this technique. The Japanese Orthopaedic Association (JOA) score was applied before and after surgery to evaluate the neurological status of the patient, and the Atlanto-dental interval (ADI) was measured before and after surgery to evaluate the atlantoaxial reduction. X-ray and CT were performed to evaluate internal fixation, atlantoaxial sequence and bone graft fusion during regular follow-up. MRI was performed to evaluate the status of atlantoaxial reduction and spinal cord compression after surgery. RESULTS: All 10 patients were successfully operated, and there were no complications such as spinal nerve and vascular injury. Postoperative clinical symptoms were significantly relieved in all patients, and postoperative JOA score and ADI were significantly improved compared with those before surgery (P < 0.05). CONCLUSIONS: The developed posterior reduction forceps for atlantoaxial dislocation can assist the simple posterior screw-rod system in the treatment of irreducible atlantoaxial dislocation to avoid the release in anterior or posterior approach and reduce the difficulty of surgery. The preliminary results of this technique are satisfactory and it has a good application prospect.
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Articulação Atlantoaxial , Luxações Articulares , Humanos , Articulação Atlantoaxial/cirurgia , Articulação Atlantoaxial/diagnóstico por imagem , Luxações Articulares/cirurgia , Luxações Articulares/diagnóstico por imagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Parafusos Ósseos , Adulto Jovem , Resultado do Tratamento , AdolescenteRESUMO
In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.
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Proteínas de Artrópodes , Braquiúros , Hemócitos , Imunidade Inata , Animais , Braquiúros/genética , Braquiúros/imunologia , Hemócitos/imunologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Imunidade Inata/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/imunologia , Regulação da Expressão Gênica/imunologia , Proliferação de CélulasRESUMO
A novel co-bonded octyl and pyridine silica (OPS) sorbent was prepared and applied for the solid phase extraction (SPE) of cyclopiazonic acid (CPA, a type of mycotoxin) in feed and agricultural products for the first time. A simple mixed-ligand one-pot reaction strategy was employed for OPS sorbent preparation. Nitrogen adsorption-desorption measurements, elemental analysis (EI), thermal gravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FT-IR) analysis demonstrated the successful immobilization of octyl and quaternary ammonium groups onto the surface of silica gel. The large specific surface area, high-density functional groups, and mixed-mode anion-exchange characteristics of these silica particles made them the ideal material for the efficient extraction of CPA. Additionally, the OPS sorbents displayed excellent batch-to-batch reproducibility, satisfactory reusability, and low cost. The SPE parameters were optimized to explore the ionic and hydrophobic interactions between CPA and the functional groups, and the ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-MS/MS) parameters were optimized to obtain a desirable extraction efficiency and high sensitivity to CPA. Meanwhile, the OPS sorbent presented a satisfactory extraction selectivity and low matrix effect. Under the optimized conditions, our developed CPA detection method was used to determine CPA level in rice, wheat flour, corn flour, peanut, and feed samples, exhibiting a lower detection limit, better linearity, higher sensitivity, and satisfactory extraction recovery rate than previously reported methods. Therefore, our method can be preferentially used as a method for the detection of CPA in agricultural products and feeds.
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Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose a significant threat to health and safety. Owing to the lack of effective antimold measures in the agricultural industry, feed ingredients such as corn, peanuts, wheat, barley, millet, nuts, oily feed, forage, and their byproducts are prone to mold and mycotoxin contamination, which can affect animal production, product quality, and safety. Cyclopiazonic acid (CPA), which is mainly biosynthesized from mevalonate, tryptophan, and diacetate units, is a myotoxic secondary metabolite produced by Penicillium and Aspergillus fungi. CPA is widely present as a copollutant with aflatoxins in various crops. Compared with some common mycotoxins such as aflatoxins, fumonisins, ochratoxins, zearalenones, and their metabolites, CPA has not been well investigated. In the United States, a survey showed that 51% of corn and 90% of peanut samples contained CPA, with a maximum level of 2.9 mg/kg. In Europe, CPA was found in Penicillium-contaminated cheeses as high as 4.0 mg/kg. Some studies have shown that CPA can cause irreversible damage to organs such as the liver and spleen in mice. Therefore, the establishment of a rapid and efficient analytical method for CPA is of great significance for the risk assessment of CPA in feeds, the development of standard limits, and the protection of feed product quality and safety. The QuEChERS method, a sample pretreatment method that is fast, simple, cheap, effective, and safe, is widely used in the analysis of pesticide residues in food. In this study, a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine CPA levels in feeds. The chromatographic separation and MS detection of CPA as well as the key factors affecting the extraction efficiency of CPA, including the type of extraction solvent, type of inorganic salt, and type and dosage of adsorbent, were optimized in detail. During the optimization of the chromatographic-separation step, the acid and salt concentrations of the mobile phase affected the separation and detection of CPA. During the optimization of the QuEChERS method, the addition of a certain amount of acetic acid improved the extraction efficiency of CPA because of its acidic nature; in addition, GCB and PSA significantly adsorbed CPA from the feed extract. Under optimal conditions, the CPA in the feed sample (1.0 g) was extracted with 2 mL of water and 4 mL of acetonitrile (ACN) containing 0.5% acetic acid. After salting out with 0.4 g of NaCl and 1.6 g of MgSO4, 1 mL of the ACN supernatant was purified by dispersive solid-phase extraction using 150 mg of MgSO4 and 50 mg of C18 and analyzed by UPLC-MS/MS. The sample was separated on a Waters HSS T3 column (100 mm×2.1 mm, 1.8 µm) using 2 mmol/L ammonium acetate aqueous solution with 0.5% formic acid and ACN as the mobile phases and then analyzed by positive electrospray ionization in multiple reaction monitoring mode. CPA exhibited good linearity in the range of 2-200 ng/mL, with a high correlation coefficient (r=0.9995). The limits of detection and quantification of CPA, which were calculated as 3 and 10 times the signal-to-noise ratio, respectively, were 0.6 and 2.0 µg/kg, respectively. The average recoveries in feed samples spiked with 10, 100, and 500 µg/kg CPA ranged from 70.1% to 78.5%, with an intra-day precision of less than 5.8% and an inter-day precision of less than 7.2%, indicating the good accuracy and precision of the proposed method. Finally, the modified QuEChERS-UPLC-MS/MS method was applied to the analysis of CPA in 10 feed samples obtained from Wuhan market. The analysis results indicated that the developed method has good applicability for CPA analysis in feed samples. In summary, an improved QuEChERS method was applied to the extraction and purification of CPA from feeds for the first time; this method provides a suitable analytical method for the risk monitoring, assessment, and standard-limit setting of CPA in feed samples.
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Ração Animal , Contaminação de Alimentos , Indóis , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Ração Animal/análise , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Indóis/análise , Micotoxinas/análiseRESUMO
Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.
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Compostos Alílicos , Proliferação de Células , Dissulfetos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Proteína Desglicase DJ-1 , Neoplasias Gástricas , Dissulfetos/farmacologia , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Compostos Alílicos/farmacologia , Humanos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Movimento Celular/efeitos dos fármacos , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.
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Metabolismo dos Lipídeos , Fármacos Neuroprotetores , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Homeostase/efeitos dos fármacos , Poríferos/química , Camundongos , Camundongos Endogâmicos C57BL , Autofagia/efeitos dos fármacos , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Policetídeos/farmacologia , HumanosRESUMO
Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.
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Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , NAD , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1 , Sirtuína 3 , Animais , Masculino , Camundongos , Ratos , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Dieta Hiperlipídica , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , NAD/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Palmítico/farmacologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 3/metabolismo , Sirtuína 3/genética , EstreptozocinaRESUMO
OBJECTIVE: Minimally invasive atlantoaxial surgery offers the benefits of reduced trauma and quicker recovery. Previous studies have focused on feasibility and technical aspects, but the lack of comprehensive safety information has limited its availability and widespread use. This study proposes to define the feasibility and range of surgical safety using the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique as a reference point. METHODS: Dissection was performed on 10 fresh cadavers to define the anatomical reference point as the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique muscle. The study aimed to analyze the safety range of minimally invasive atlantoaxial fusion surgery by measuring the distance between the anatomical reference point and the transverse foramen of the axis, the distance between the anatomical reference point and the superior border of the posterior arch of the atlas, and the distance between the anatomical reference point and the spinal canal. Measurements were compared using Student's t test. RESULTS: The point where the occipital greater nerve intersects with the inferior border of the inferior cephalic oblique muscle was defined as the anatomical marker for minimally invasive posterior atlantoaxial surgery. The distance between this anatomical marker and the transverse foramen of the axis was measured to be 9.32 ± 2.04 mm. Additionally, the distance to the superior border of the posterior arch of the atlas was found to be 21.29 ± 1.93 mm, and the distance to the spinal canal was measured to be 11.53 ± 2.18 mm. These measurement results can aid surgeons in protecting the vertebral artery and dura mater during minimally invasive posterior atlantoaxial surgery. CONCLUSIONS: The intersection of the greater occipital nerve with the inferior border of the inferior cephalic oblique muscle is a safe and reliable anatomical landmark in minimally invasive posterior atlantoaxial surgery.
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Vértebras Cervicais , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Vértebras Cervicais/cirurgia , Artéria Vertebral , CadáverRESUMO
Covalent organic framework (COF) nanosheets have recently garnered great attention as a new class of functional materials. As one of the sustainable processes, however, the photocatalytic organic synthesis in water has not been investigated using COF nanosheets as a photocatalyst to date. Herein, we reported the synthesis of a fully conjugated COF nanosheets with carboxyl functional group through a cooperative strategy of chemical exfoliation and group transformation. The new COF nanosheets was found to be an efficient heterogeneous photocatalyst for a wide range of organic synthesis including selective oxidation of sulfides and oxidative coupling of benzylamines in water under visible-light illumination. This work contributes a new roadmap for the design and synthesis of functional COF-based nanosheets, but also further extends the application boundary of the ultrathin COF nanosheets.
RESUMO
BACKGROUND: To analyze and compare the biomechanical characteristics of the new combined cervical fusion device (NCCFD) and the traditional cage-plate construct (CPC) to ascertain its effectiveness in anterior cervical discectomy and fusion (ACDF) using finite element analysis. METHODS: A finite element model of the cervical spine, inclusive of the occipital bone was created and validated. In the ACDF model, either CPC or NCCFD was implanted at the C2-C3 segment of the model. A pure moment of 1.0 Nm combined with a follower load of 50 N was directed onto the superior surfaces of the occipital bone to determine flexion, extension, lateral bending (left and right), and axial rotation (left and right). The range of motion (ROM), stress distribution at the bone-implant interface, and facet joint forces were investigated and compared between CPC and NCCFD systems. RESULT: The results showed that the ROMs of the fused levels in both models were nearly zero, and the motions of the unfused segments were similar. In addition, the maximum displacement exhibited nearly identical values for both models. The maximum stress of NCCFD screws in lateral bending and rotational conditions is significantly higher than that of the CPC, while the NCCFD model's maximum stress remains within an acceptable range. Comparing the maximum fusion stress, it was found that the CPC experiences much lower fusion stress in anterior flexion and extension than the NCCFD, with no significant difference between the two in lateral bending and rotational states. Stress on the cage was mainly concentrated on both sides of the wings. Comparing the maximum IDP in the CPC and NCCFD, it was observed that maximum stresses rise in extension and lateral bending for both models. Lastly, stress distributions of the facet joints were generally similar across the two devices. CONCLUSION: NCCFD not only provides the same level of biomechanical stability as CPC but also avoids postoperative complications associated with uneven force damage to the implant. The device offers a novel surgical alternative for ACDF in C2-C3 level.
Assuntos
Discotomia , Fusão Vertebral , Análise de Elementos Finitos , Fenômenos Biomecânicos , Discotomia/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Placas Ósseas , Fusão Vertebral/métodos , Amplitude de Movimento ArticularRESUMO
We have discovered intrinsically fibrogenic mesenchymal progenitor cells (MPCs) in the human idiopathic pulmonary fibrosis (IPF) lung. IPF MPCs display a durably distinct transcriptome, suggesting that they have undergone epigenetic modifications. Prior studies indicate that the chromatin remodeler Brg1 associates with the arginine methyltransferase PRMT5 to epigenetically regulate transcription factors. We hypothesize that a Brg1/PRMT5 nuclear complex epigenetically regulates critical nodes in IPF MPC self-renewal signaling networks. IPF and control MPCs were isolated from primary mesenchymal cell lines established from IPF and control patients. RNA-sequencing identified increased expression of the FOXO1 transcription factor in IPF MPCs compared with controls, a result we confirmed by Q-PCR and Western blot analysis. Immunoprecipitation identified a CD44/Brg1/PRMT5 nuclear complex in IPF MPCs. Chromatin immunoprecipitation assays showed that PRMT5 and its methylation mark H3R2me2 are enriched on the FOXO1 promoter. We show that loss of Brg1 and PRMT5 function decreases FOXO1 expression and impairs IPF MPC self-renewal, and that loss of FOXO1 function decreases IPF MPC self-renewal and expression of the SOX2 and OCT4 stemness markers. Our findings indicate that the FOXO1 gene is overexpressed in IPF MPCs in a CD44/Brg1/PRMT5 nuclear complex-dependent manner. Our data suggest that Brg1 alters chromatin accessibility, enriching PRMT5 occupancy on the FOXO1 promoter, and PRMT5 methylates histone H3 arginine 2 (H3R2) on the FOXO1 promoter, increasing its expression. Our data are in accord with the concept that this coordinated interplay is responsible for promoting IPF MPC self-renewal and maintaining a critical pool of fibrogenic MPCs that drive IPF progression.NEW & NOTEWORTHY Our research offers valuable understanding regarding the epigenetic control of IPF MPC. The data we obtained strongly support the idea that the coordination between chromatin remodeling and histone methylation plays a key role in regulating transcription factors. Specifically, our findings indicate that FOXO1, an essential transcription factor, likely governs the self-renewal of IPF MPC, which is crucial for maintaining a critical pool of fibrogenic MPCs. This interplay could be an important therapeutic target.