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Two-component signal transduction systems (TCSs) are regulatory systems widely distributed in eubacteria, archaea, and a few eukaryotic organisms, but not in mammalian cells. A typical TCS consists of a histidine kinase and a response regulator protein. Functional and mechanistic studies on different TCSs have greatly advanced the understanding of cellular phosphotransfer signal transduction mechanisms. In this concept paper, we focus on the His-Asp phosphotransfer mechanism, the ATP synthesis function, antimicrobial drug design, cellular biosensors design, and protein allostery mechanisms based on recent TCS investigations to inspire new applications and future research perspectives.
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Bactérias , Transdução de Sinais , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Histidina Quinase/metabolismo , Técnicas Biossensoriais , Trifosfato de Adenosina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Desenho de Fármacos , Proteínas Quinases/metabolismo , Proteínas Quinases/químicaRESUMO
Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post-traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL-QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full-thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL-QN15 treatment. Furthermore, RL-QN15 promoted the proliferation, migration, and axonal length of neuron-like PC12 cells, which was likely associated with activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL-QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL-QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL-QN15 peptide-based therapeutics against diabetic skin wounds.
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Diabetes Mellitus Experimental , Proteínas Proto-Oncogênicas c-akt , Ratos , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases , Pele , Fibras Nervosas/metabolismo , Sensação , Peptídeos/farmacologia , Regeneração Nervosa/fisiologiaRESUMO
Dietary flavonoids exhibit a variety of physiological functions in regulating glucose and lipid metabolism, improving cardiovascular function, and enhancing stress resistance. However, poor intestinal absorption limits their health benefits. Previous studies on improving the absorption efficiency of flavonoids have focused on targeted release, enhanced gastrointestinal stability and prolonged retention time in digestive tract. But less attention has been paid to promoting the uptake and transport of flavonoids by intestinal epithelial cells through modulation of transporter protein-mediated pathways. Interestingly, some dietary nutrients have been found to modulate the expression or function of transporter proteins, thereby synergistically or antagonistically affecting flavonoid absorption. Therefore, this paper proposed an innovative regulatory strategy known as the "intestinal transport protein-mediated pathway" to promote intestinal absorption of dietary flavonoids. The flavonoid absorption mechanism in the intestinal epithelium, mediated by intestinal transport proteins, was summarized. The functional differences between the uptake transporter and efflux transporters during flavonoid trans-intestinal cellular transport were discussed. Finally, from the perspective of nutritional synergy promotion of absorption, the feasibility of promoting flavonoid intestinal absorption by regulating the expression/function of transport proteins through dietary nutrients was emphasized. This review provides a new perspective and developing precise dietary nutrient combinations for efficient dietary flavonoid absorption.
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We propose to coherently control the ultracold 2KRb â K2 + Rb2 reaction product state distribution via quantum interference. By leveraging that the nuclear spin degrees of freedom in the reaction maintain coherence, which was demonstrated in Liu, Zhu et al., arXiv, 2023, arXiv:2310.07620, https://doi.org/10.48550/arXiv.2310.07620, we explore the concept of a "reaction interferometer". Such an interferometer involves splitting one KRb molecular cloud into two, imprinting a well-defined relative phase between them, recombining the clouds for reactions, and measuring the product state distribution. We show that the interference patterns provide a mechanism to coherently control the product states, and specific product channels also serve as an entanglement witness of the atoms in the reactant KRb molecule.
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This review aims to synthesize current knowledge on the incidence, characteristics and management of wounds and injuries among professional ice hockey athletes, with the specific focus on the emerging population of Chinese female players. An extensive literature search was conducted across several databases to gather data on injury patterns and wounds, causes, severity and prevention strategies in ice hockey. Special attention was given to studies involving female athletes and unique challenges faced by players in developing regions like China. The review also examined the impact of training modalities, protective equipment and medical interventions on injury rates. The findings reveal a significant seasonal fluctuation in wound incidence, with marked reduction following the preseason period. This trend underscores the effectiveness of adjusted training programmes and essential role of medical teams in injury prevention and rehabilitation. Analysis did not show significant difference in wound rates between technical and physical training sessions, suggesting that injuries are pervasive risk across all training activities. Skating, collisions and inadequate warm-ups were identified as the leading causes of wounds, highlighting areas for targeted preventive measures. The distribution of wounds across various body regions pointed to knee, lower back and wrist as the most vulnerable sites, necessitating focused protection and training adjustments. Ice hockey, particularly among female athletes in China, presents complex injury landscape characterized by the wide range of wounds. The study emphasizes the necessity of comprehensive, multidisciplinary approach to injury prevention that includes training modifications, enhanced protective gear and strategic medical oversight. By addressing the specific causes and patterns of injuries identified, stakeholders can better protect athletes from the inherent risks of the sport, promote safer play and extend career longevity.
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Atletas , Hóquei , Feminino , Humanos , China/epidemiologia , Hóquei/lesões , Incidência , Extremidade Inferior , MasculinoRESUMO
ATP (adenosine triphosphate) is a vital energy source for living organisms, and its biosynthesis and precise concentration regulation often depend on macromolecular machinery composed of protein complexes or complicated multidomain proteins. We have identified a single-domain protein HK853CA derived from bacterial histidine kinases (HK) that can catalyze ATP synthesis efficiently. Here, we explored the reaction mechanism and multiple factors that influence this catalysis through a combination of experimental techniques and molecular simulations. Moreover, we optimized its enzymatic activity and applied it as an ATP replenishment machinery to other ATP-dependent systems. Our results broaden the understanding of ATP biosynthesis and show that the single CA domain can be applied as a new biomolecular catalyst used for ATP supply.
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Bactérias , Proteínas de Bactérias , Histidina Quinase/metabolismo , Proteínas de Bactérias/metabolismo , Bactérias/metabolismo , Trifosfato de Adenosina/metabolismo , CatáliseRESUMO
Hyperuricemia is a clinical disease characterized by a continuous increase in uric acid (UA) due to purine metabolism disorder. As current drug treatments are limited, it is imperative to explore new drugs that offer better safety and efficacy. In this study, Nephila clavata toxin gland homogenates were isolated and purified by exclusion chromatography and high-performance liquid chromatography, resulting in the identification and isolation of a short peptide (NCTX15) with the sequence 'QSGHTFK'. Analysis showed that NCTX15 exhibited no cytotoxicity in mouse macrophages or toxic and hemolytic activity in mice. Notably, NCTX15 inhibited UA production by down-regulating urate transporter 1 and glucose transporter 9 and up-regulating organic anion transporter 1, thus promoting UA excretion. In addition, NCTX15 alleviated the inflammatory response and renal injury by inhibiting the expression of inflammatory factors interleukin-6, interleukin-1ß, tumor necrosis factor alpha, NLR family, pyrin domain-containing 3, and pyroptosis-related factor gasdermin D. These results indicate that NCTX15 displayed urate-lowering, anti-inflammatory, and analgesic effects. As the first urate-reducing short peptide isolated from a spider toxin gland homogenate, NCTX15 exhibits considerable potential as a novel drug molecule for anti-gout and hyperuricemia treatment.
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Gota , Hiperuricemia , Camundongos , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/metabolismo , Gota/metabolismo , Rim/metabolismo , Interleucina-6/metabolismo , Xantina Oxidase/metabolismoRESUMO
BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.
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MicroRNAs , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Ratos , NF-kappa B , Quinase I-kappa B , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Proteínas Serina-Treonina Quinases , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
BACKGROUND: Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants. RESULTS: AITC significantly reduced the population of RKNs in soil (p < 0.0001) and showed an excellent RKN disease control effect within 6 months after sowing Panax notoginseng (p < 0.0001). The seedling survival rate of 2-year-old P. notoginseng was approximately 1.7-fold higher after soil treatment with AITC (p = 0.1008). 16S rRNA sequencing indicated that the AITC treatment affected bacterial richness rather than diversity in consecutively cultivated (CC) soil. Furthermore, biomarkers with statistical differences between AITC-treated and untreated CC soil showed that Pirellulales (order), Pirellulaceae (family), Pseudomonadaceae (family), and Pseudomonas (genus) played important roles in the AITC-treated group. In addition, the microbiome functional phenotypes predicted using the BugBase tool suggested that AITC treatment is more conducive to improving CC soil through changes in the bacterial community structure. Crucially, our research also suggested that AITC soil treatment significantly increases soil organic matter (p = 0.0055), total nitrogen (p = 0.0054), and available potassium (p = 0.0373), which promotes the survival of a succeeding medicinal plant (Polygonatum kingianum). CONCLUSION: AITC is an ecologically friendly soil treatment that affects the top 10 bacterial richness but not diversity. It could also provide a basis for a useful agricultural soil management measure to alleviate soil sickness.
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Plantas Medicinais , Solo , Solo/química , Fumigação , RNA Ribossômico 16S/genética , Microbiologia do Solo , Bactérias/genéticaRESUMO
BACKGROUND AND AIMS: This study investigates the expression of novel adipocytokines and inflammatory cells infiltration in epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) between 27 coronary artery disease (CAD) and 21 non-CAD (NCAD) patients enrolled from September 2020 to September 2021. METHODS AND RESULTS: Serum, gene, and protein expression levels of the novel adipocytokines were determined using ELISA, RT-qPCR, and western blot analyses. The number of blood vessels and adipocytes morphology were measured via hematoxylin-eosin staining, and inflammatory cells infiltration was examined via immunohistochemistry. Serum ANGPTL8, CTRP5, and Wnt5a levels were higher in the CAD than in the NCAD group, while serum CTRP3, Sfrp5, and ZAG levels were lower in the CAD than in the NCAD group. Compared to the EAT of NCAD and SAT of CAD patients, the EAT of CAD patients had higher mRNA levels of ANGPTL8, CTRP5, and Wnt5a while lower levels of CTRP3, Sfrp5, and ZAG; higher protein expression levels of ANGPTL8 and CTRP5 but lower levels of CTRP3; more blood vessels; and higher infiltration rates of macrophages (CD68 + ), pro-inflammatory M1 macrophages (CD11c + ), mast cells (Tryptase + ), T lymphocytes (CD3 + ), and B lymphocytes (CD20 + ) but lower infiltration rates of anti-inflammatory M2 macrophages (CD206 + ). CONCLUSION: Novel adipocytokines and inflammatory cells infiltration are dysregulated in human EAT, and could be important pathophysiological mechanisms and novelly promising medicating targets of CAD.
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Doença da Artéria Coronariana , Hormônios Peptídicos , Humanos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Tecido Adiposo/metabolismo , Gordura Subcutânea/metabolismo , Adipocinas/metabolismo , Inflamação/metabolismo , Pericárdio/metabolismo , Proteína 8 Semelhante a AngiopoietinaRESUMO
Excessive melanogenesis leads to hyperpigmentation, which is one of the common skin conditions in humans. Existing whitening cosmetics cannot meet market needs due to their inherent limitations. Thus, the development of novel skin-whitening agents continues to be a challenge. The peptide OA-VI12 from the skin of amphibians at high altitude has attracted attention due to its remarkable anti light damage activity. However, whether OA-VI12 has the skin-whitening effect of inhibiting melanogenesis is still. Mouse melanoma cells (B16) were used to study the effect of OA-VI12 on cell viability and melanin content. The pigmentation model of C57B/6 mouse ear skin was induced by UVB and treated with OA-VI12. Melanin staining was used to observe the degree of pigmentation. MicroRNA sequencing, quantitative real-time PCR (qRT-PCR), immunofluorescence analysis and Western blot were used to detect the change of factor expression. Double luciferase gene report experiment was used to prove the regulatory relationship between miRNA and target genes. OA-VI12 has no effect on the viability of B16 cells in the concentration range of 1-100 µM and significantly inhibits the melanin content of B16 cells. Topical application of OA-VI12, which exerted transdermal potency, prevented UVB-induced pigmentation of ear skin. MicroRNA sequencing and double luciferase reporter analysis results showed that miR-122-5p, which directly regulated microphthalmia-associated transcription factor (Mitf), had significantly different expression before and after treatment with OA-VI12. Mitf is a simple helix loop and leucine zipper transcription factor that regulates tyrosinase (Tyr) expression by binding to the M-box promoter element of Tyr. qRT-PCR, immunofluorescence analysis and Western blot showed that OA-VI12 up-regulated the expression of miR-122-5p and inhibited the expression of Mitf and Tyr. The effects of OA-VI12 on melanogenesis inhibition in vitro and in vivo may involve the miR-122-5p/Mitf/tyr axis. OA-VI12 represents the first report on a natural amphibian-derived peptide with skin-whitening capacity and the first report of miR-122-5p as a target for regulating melanogenesis, thereby demonstrating its potential as a novel skin-whitening agent and highlighting amphibian-derived peptides as an underdeveloped resource.
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Melaninas , MicroRNAs , Humanos , Animais , Camundongos , Melaninas/metabolismo , Monofenol Mono-Oxigenase/genética , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Fator de Transcrição Associado à Microftalmia/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Luciferases/metabolismo , Peptídeos/farmacologia , Linhagem Celular TumoralRESUMO
BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of differentiated thyroid cancer. Early identification of patients at higher risk of recurrence may allow to improve relevant follow-up strategies and plan tailored treatment. Inflammation play an important role in the prognosis of cancer. We aimed to explore the predictive value of systemic inflammatory markers in PTC recurrence. METHODS: We retrospectively enrolled 200 consecutive patients who were diagnosed with PTC and underwent curative resection at Lianyungang Oriental Hospital between January 2006 and December 2018. Clinicopathological characteristics, preoperative hematologic results were analyzed. The optimal cutoff values were calculated using x-tile software. The multivariate logistic regression and univariable survival analysis were performed by SPSS. RESULTS: Multivariable analysis showed that lymph node metastases (odds ratio [OR] = 2.506, 95% confidence interval [CI]: 1.226-5.119, p = 0.012) and higher monocyte-to-lymphocyte ratio (MLR) (OR = 2.100, 95% CI: 1.042-4.233, p = 0.038) were independent prognostic factors for tumor recurrence. The cutoff value 0.22 of MLR significantly predicted recurrence at 53.3% sensitivity and 67.9% specificity. Patients with MLR ≥ 0.22 exhibited significantly poor long-term prognosis (46.8%) compared to the counterpart (76.8%, p = 0.0004). CONCLUSIONS: Preoperative MLR significantly predicted PTC recurrence after curative resection, which may provide clues for early identification of patients at higher risk of PTC recurrence.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Estudos Retrospectivos , Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/patologia , Prognóstico , Recidiva Local de Neoplasia/cirurgia , TireoidectomiaRESUMO
BACKGROUND: Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing. METHODS: Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing. RESULTS: The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3ß to activate Wnt/ß-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. CONCLUSIONS: OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/ß-catenin molecular axis). Moreover, miR-632 also activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.
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MicroRNAs , beta Catenina , Camundongos , Ratos , Animais , beta Catenina/metabolismo , Receptor 4 Toll-Like , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Cicatrização , Peptídeos/farmacologia , MicroRNAs/genética , Inflamação , Proliferação de Células/genéticaRESUMO
BACKGROUND: Active peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets. METHODS: Bioinformatics analysis and luciferase assay were adopted to determine microRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms. RESULTS: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-ß type II receptor (TGFßR2) expression and an inhibitory effect on activation of the downstream SMAD family member 2 (Smad2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice. CONCLUSION: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFßR2/Smad2/p38 molecular axes, thus providing a promising new pro-repair drug target.
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MicroRNAs , Animais , Camundongos , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Baixo , Movimento Celular/genética , CicatrizaçãoRESUMO
There is currently limited information on the prognostic value of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) score for patients with acute coronary syndrome (ACS). We aimed to explore the predictive value of a dNLR-PNI score on the long-term prognosis of patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 1773 patients with ACS who underwent PCI were consecutively enrolled from January 2016 to December 2018. The cutoff values of dNLR and PNI to predict major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves. The patients were divided into three groups based on the dNLR-PNI score, and Kaplan-Meier curves and Cox regression models were used for survival analysis. The endpoints were MACE, including all-cause mortality and rehospitalisation for severe heart failure during follow-up. A total of 1542 patients with ACS who underwent PCI were included. Kaplan-Meier curves showed that a higher level of dNLR, PNI, or dNLR-PNI score was associated with a higher risk of MACE (all p < .001). In multivariate Cox regression models, the dNLR-PNI two score (hazard ratio 3.049, 95% confidence interval 1.503-6.184, p = .002) was found to be an independent predictor of all-cause mortality and rehospitalization for severe heart failure. A high dNLR-PNI score was independently associated with a higher risk of developing MACE in patients with ACS undergoing PCI. The dNLR-PNI score may be a useful prognostic parameter for identifying high-risk ACS patients after PCI.
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Síndrome Coronariana Aguda , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Humanos , Prognóstico , Avaliação Nutricional , Neutrófilos , Intervenção Coronária Percutânea/efeitos adversos , Linfócitos , Insuficiência Cardíaca/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important. METHODS: BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription-quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-ß2 axis. RESULTS: The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-ß2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-ß2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo. CONCLUSIONS: HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-ß2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.
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MicroRNAs , RNA Circular , Venenos de Escorpião , Fator de Crescimento Transformador beta2 , Animais , Camundongos , Inflamação , Camundongos Endogâmicos BALB C , MicroRNAs/genética , NF-kappa B , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Fator de Crescimento Transformador beta2/genética , RNA Circular/genéticaRESUMO
Due to the unstable chemical properties and poor water solubility of carotenoids, their processing adaptation and oral bioavailability are poor, limiting their application in hydrophilic food systems. Lipid-biomacromolecular compounds can be excellent carriers for carotenoid delivery by taking full advantage of the solubilization of lipids to non-polar nutrients and the water dispersion and gastrointestinal controlled release properties of biomacromolecules. This paper reviewed the research progress of lipid-biomacromolecular compounds as encapsulation and delivery carriers of carotenoids and summarized the material selection and preparation methods for biomacromolecular compounds. By considering the interaction between the two, this paper briefly discussed the effect of these compounds on carotenoid water solubility, stability, and bioavailability, emphasizing their delivery effect on carotenoids. Finally, various challenges and future trends of lipid-biomacromolecular compounds as carotenoid delivery carriers were discussed, providing new insight into efficient loading and delivery of carotenoids.
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Dietary lipids are key ingredients during cooking, processing, and seasoning of carotenoid-rich fruits and vegetables, playing vitals in affecting the absorption and utilization of carotenoids for achieving their health benefits. Besides, dietary lipids have also been extensively studied to construct various delivery systems for carotenoids, such as micro/nanoparticles, micro/nanoemulsions, and liposomes. Currently, the efficacies of these techniques on improving carotenoid bioavailability are often evaluated using the micellization rate or "bioaccessibility" based on in vitro models. However, recent studies have found that dietary lipids may also affect the carotenoid uptake via intestinal epithelial cells and the efflux of intracellular chyle particles via lipid transporters. An increasing number of studies reveal the varied impact of different dietary lipids on the absorption of different carotenoids and some lipids may even have an inhibitory effect. Consequently, it is necessary to clarify the relationship between the addition of dietary lipids and the intestinal absorption of carotenoid to fully understand the role of lipids during this process. This paper first introduces the intestinal absorption mechanism of carotenoids, including the effect of bile salts and lipases on mixed micelles, the types and regulation of lipid transporters, intracellular metabolizing enzymes, and the efflux process of chyle particles. Then, the regulatory mechanism of dietary lipids during intestinal carotenoid absorption is further discussed. Finally, the importance of selecting the dietary lipids for the absorption and utilization of different carotenoids and the design of an efficient delivery carrier are emphasized. This review provides suggestions for precise dietary carotenoid supplementation and offere an important reference for constructing efficient transport carriers for liposoluble nutrients.
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Detection of AC magnetic fields at the nanoscale is critical in applications ranging from fundamental physics to materials science. Isolated quantum spin defects, such as the nitrogen-vacancy center in diamond, can achieve the desired spatial resolution with high sensitivity. Still, vector AC magnetometry currently relies on using different orientations of an ensemble of sensors, with degraded spatial resolution, and a protocol based on a single NV is lacking. Here we propose and experimentally demonstrate a protocol that exploits a single NV to reconstruct the vectorial components of an AC magnetic field by tuning a continuous driving to distinct resonance conditions. We map the spatial distribution of an AC field generated by a copper wire on the surface of the diamond. The proposed protocol combines high sensitivity, broad dynamic range, and sensitivity to both coherent and stochastic signals, with broad applications in condensed matter physics, such as probing spin fluctuations.
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Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) are anatomically close to the myocardium and may influence cardiovascular pathology. Thus, in this study, we aim to assess whether EAT and PAT volumes were associated with coronary artery calcification score (CCS) in patients with suspected coronary artery disease (CAD), especially in overweight and obese individuals.We included consecutive patients with suspected CAD in whom EAT volume, PAT volume, and CCS were measured via computed tomography between September 2015 and June 2017 at the Affiliated Hospital of Chengde Medical University, China. Logistic regression models were applied to analyze the risk factors for CCS ≥ 100 Agatston units (AU) and in different body mass index (BMI) subgroups.EAT and PAT volumes were noted to be higher in people with BMI ≥ 24 kg/m2, BMI ≥ 28 kg/m2, hyperlipidemia, hypertension, diabetes, stroke, and CCS ≥ 100 AU (P < 0.05). After adjusting for the traditional CAD factors, we found that EAT and PAT volumes were independent risk factors for CCS ≥ 100 AU (odds ratio, 3.001; 95% confidence interval, 1.900-4.740, P < 0.001). In patients with CCS ≥ 100 AU, the EAT and PAT volumes were noted to be greater in the BMI ≥ 24 kg/m2 and BMI ≥ 28 kg/m2 subgroups than in the BMI < 24 kg/m2 and BMI < 28 kg/m2 subgroups, respectively (P < 0.05).Our results indicate that EAT and PAT volumes may be clinical predictors for a CCS ≥ 100 AU, especially in overweight and obese individuals.