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Interactions between proteins and polysaccharides could improve protein functional properties. Most studies focus on the formation of complex coacervates at pHs < pI. Much less attention has been given to the interactions at pHs > pI, especially when the mixtures are heated. The objective of this study was to investigate the emulsification properties of heated whey protein isolate (WPI) and pectin complexes formed at near neutral pHs. Heated soluble complexes (Cpxs) were formed by heating mixed WPI (3 wt% protein) and pectin (0 to 0.60 wt%) at pH 6.0, 6.5, or 7.0 at 85 °C for 30 min. Emulsions (5 wt% oil, 0.5 wt% protein, and pH 5.5) were characterized by measuring droplet size, zeta potential, rheological properties, and creaming stability. The results showed that, regardless of heating pH, Cpxs formed more stable emulsions with significantly smaller droplet sizes, higher negative charges, and less shear-thinning behavior in comparison to emulsions stabilized by heated WPI (p < 0.05). At fixed pectin concentrations, the emulsions stabilized by Cpx formed at pH 7.0 were the most stable. Increasing pectin concentrations led to a decrease in mean droplet sizes and an increase in negative charge. Maximum stability was achieved with the emulsion stabilized by Cpx formed with 0.60 wt% pectin at pH 7.0. The formation of Cpxs under proper conditions will allow for the utilization of WPI in a wider range of applications and fulfill the consumer need for clean label food products.
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Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.
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Antibacterianos , Pie Diabético , Humanos , Pie Diabético/microbiología , Pie Diabético/epidemiología , China/epidemiología , Antibacterianos/uso terapéutico , Incidencia , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológicoRESUMEN
Silver nanowire (AgNW) transparent electrodes are considered as a promising candidate for applications in flexible optoelectronic devices. However, it remains a great challenge to obtain flexible AgNW electrodes with excellent optoelectrical properties and mechanical flexibility. Here, highly stable Ag nanoparticle (AgNP)-enhanced plasmonic AgNW electrodes are demonstrated via the controllable in situ growth of AgNPs at the AgNW junctions and introduction of an l-histidine (l-His) wrapping layer. The flexible transparent electrodes of AgNW-AgNP/l-His possess a low sheet resistance (Rsh) of â¼17.5 Ω sq-1, a high transmittance of â¼92.5% (550 nm), and a robust mechanical stability (100,000 bending cycles). Benefiting from plasmon-coupling effects, flexible polymer light-emitting devices (FPLEDs) with AgNW-AgNP/l-His electrodes present a current efficiency (CE) of â¼14.8 cd A-1 and an external quantum efficiency (EQE) of â¼5.6%, constituting â¼80% and â¼75% increases compared to those of the reference devices with AgNW electrodes, respectively. Additionally, the laminated flexible transparent PLEDs (FT-PLEDs) are demonstrated by integrating polydimethylsiloxane/AgNW-AgNP anodes by a soft lamination process. The FT-PLEDs present a CE of â¼7.1 cd A-1 (cathode side: â¼3.9 cd A-1; anode side: â¼3.2 cd A-1) and an EQE of â¼2.7% (cathode side: â¼1.5%; anode side: â¼1.2%). Furthermore, the FPLEDs and FT-PLEDs exhibit robust mechanical durability, maintaining â¼89% and â¼86% of their initial luminance after 1000 bending cycles at a bending radius of 2 mm, respectively. This work opens up a new avenue for the development of high performance and stable flexible optoelectronic devices.
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Spinal facet joint osteoarthritis (FJOA) is an OA disease with pathogenesis and progression uncovered. Our present study was performed to elucidate the role of DNM3OS on spinal FJOA. In this study, spine facet joint tissue of patients were collected. In vitro and in vivo models were constructed with SW1353 cells and rats. Hematoxylin and eosin (HE) staining, Safranin O-fast Green, Alcian blue staining, and Tolueine blue O (TBO) staining were employed for histology analyses. Quantitative PCR, western blotting, and Immunofluorescence were performed to evaluate the expression of genes. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay analysis. Cell Counting Kit-8 and flow cytometry were used for cell activity and apoptosis evaluation. The targeting sites between microRNA (miR)-127-5p and cadherin 11 (CDH11) were predicted TargetScan and miRbase database and confirmed by Dual-luciferase reporter assays. CHIP and EMS assay were employed to confirm the binding of LEF1and DNM3OS promoter. Our results showed that DNM3OS was found to upregulated, while miR-127-5p was downregulated in severe FJOA patients and inflammation-induced chondrosarcoma SW1353 cells. DNM3OS reduced cell activity, induced cell apoptosis and extracellular matrix (ECM) degradation by sponging miR-127-5p in vitro. miR-127-5p targeted CDH11 and inhibited wnt3a/ß-catenin pathway to regulate OA in vitro. LEF1 promoted DNM3OS transcription to form a positively feedback in activated wnt3a/ß-catenin pathway. In vivo rat model also confirmed that DNM3OS aggravated FJOA. In summary, DNM3OS/miR-127-5p/CDH11 enhanced Wnt3a/ß-Catenin/LEF-1 pathway to form a positive feedback and aggravate spinal FJOA.
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Electrospun scaffolds play important roles in the fields of regenerative medicine and vascular tissue engineering. The aim of the research described here was to develop a vascular scaffold that mimics the structural and functional properties of natural vascular scaffolding. The mechanical properties of artificial vascular tissue represent a key issue for successful transplantation in small diameter engineering blood vessels. We blended silk fibroin (SF) and fibrin to fabricate a composite scaffold using electrospinning to overcome the shortcomings of fibrin with respect to its mechanical properties. Subsequently, we then carefully investigated the morphological, mechanical properties, hydrophilicity, hemocompatibility, degradation, cytocompatibility and biocompatibility of the SF/fibrin (0:100), SF/fibrin (15:85), SF/fibrin (25:75), and SF/fibrin (35:65) scaffolds. Based on these in vitro results, we implanted SF/fibrin (25:75) vascular scaffold subcutaneously and analyzed its in vivo degradation and histocompatibility. The fiber structure of the SF/fibrin hybrid scaffold was smooth and uniform, and its fiber diameters were relatively small. Compared with the fibrin scaffold, the SF/fibrin scaffold clearly displayed increased mechanical strength, but the hydrophilicity weakened correspondingly. All of the SF/fibrin scaffolds showed excellent blood compatibility and appropriate biodegradation rates. The SF/fibrin (25:75) scaffold increased the proliferation and adhesion of MSCs. The results of animal experiments confirmed that the degradation of the SF/fibrin (25:75) scaffold was faster than that of the SF scaffold and effectively promoted tissue regeneration and cell infiltration. All in all, the SF/fibrin (25:75) electrospun scaffold displayed balanced and controllable biomechanical properties, degradability, and good cell compatibility. Thus, this scaffold proved to be an ideal candidate material for artificial blood vessels.
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Fibroínas , Ingeniería de Tejidos , Animales , Ingeniería de Tejidos/métodos , Fibroínas/farmacología , Fibroínas/química , Andamios del Tejido/química , Fibrina , Seda/químicaRESUMEN
Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA by altering M1/M2-polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL-1ß. To create M1-polarized macrophages in vitro, rat bone marrow-derived macrophages (rBMDMs) were treated with 100 ng/mL LPS. To mimic OA conditions observed in vivo, a co-culture system of chondrocytes and macrophages was established. ATP release assays, immunofluorescence assays, Fluo-4 AM staining, Transwell assays, ELISA assays, and flow cytometry were performed. Male adult Sprague-Dawley (SD) rats were used to create an OA model. Histological analyses, including H&E, and safranin O-fast green staining were performed. Our data showed a quercetin-mediated suppression of calcium ion influx and ATP release, with concurrent downregulation of TRPV1 and P2X7 in the chondrocytes treated with IL-1ß. Activation of TRPV1 abolished the quercetin-mediated effects on calcium ion influx and ATP release in chondrocytes treated with IL-1ß. In the co-culture system, overexpression of P2X7 in macrophages attenuated the quercetin-mediated effects on M1 polarization, migration, and inflammation. Either P2X7 or NLRP3 knockdown attenuated IL-1ß-induced M1/M2 polarization, migration, and inflammation. Moreover, overexpression of TRPV1 reduced the quercetin-mediated suppressive effects on OA by promoting M1/M2-polarized macrophages in vivo. Collectively, our data showed that quercetin-induced suppression of TRPV1 leads to a delay in OA progression by shifting the macrophage polarization from M1 to M2 subtypes via modulation of the P2X7/NLRP3 pathway.
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Osteoartritis , Quercetina , Animales , Masculino , Ratas , Adenosina Trifosfato/metabolismo , Calcio/metabolismo , Inflamación/metabolismo , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteoartritis/tratamiento farmacológico , Quercetina/farmacología , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.
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Low-cost fabric-based top-emitting polymer light-emitting devices (Fa-TPLEDs) have aroused increasing attention due to their remarkable potential applications in wearable displays. However, it is still challenging to realize efficient all-solution-processed devices from bottom electrodes to top electrodes with large-scale fabrication. Here, a smooth reflective Ag cathode integrated on fabric by one-step silver mirror reaction and a composite transparent anode of polydimethylsiloxane/silver nanowires/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) via a water-assisted peeling method are presented, both of which possess excellent optoelectrical properties and robust mechanical flexibility. The Fa-TPLEDs are constructed by spin-coating functional layers on the bottom reflective cathodes and laminating the top transparent anodes. The Fa-TPLEDs show a current efficiency of 16.3 cd A-1 , an external quantum efficiency of 4.9% and angle-independent electroluminescence spectra. In addition, the Fa-TPLEDs possess excellent mechanical stability, maintaining a current efficiency of 14.3 cd A-1 after 200 bending cycles at a radius of 4 mm. The results demonstrate that the integration of solution-processed reflective cathodes and transparent anodes sheds light on a new avenue to construct low-cost and efficient fabric-based devices, showing great potential applications in emerging smart flexible/wearable electronics.
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Tumour necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. TNF-α slows down osteogenic differentiation, which may contribute to poor bone development in the inflammatory microenvironment. TNF-α inhibits osteogenic differentiation by activating the JAK-STAT3 pathway, of which Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) is a key protein in the JAK-STAT3 pathway. We investigated whether and how ELP2 activation mediates the TNF-α-induced pyroptosis during osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α exposure causes cell pyroptosis in an inflammatory microenvironment during osteoblastic differentiation. Bioinformatics, protein docking model and co-immunoprecipitation analysis revealed an association between ELP2, STAT3 and NLRP3. Forced ELP2 expression promoted MC3T3-E1 cells pyroptosis, with an increase in the expression of STAT3, NLRP3 inflammasome, GSDMD/GSDME, osteoblast marker genes, and the activity of alkaline phosphatase. In contrast, ELP2 silencing ameliorated MC3T3-E1 cells pyroptosis, and osteogenic differentiation, especially after TNF-α stimulation. The TNF-α-induced cells pyroptosis during osteoblastic differentiation was therefore mediated by ELP2. These results suggest that ELP2 is upregulated at the pyroptosis of MC3T3-E1 cells and inhibits osteogenic differentiation in response to TNF-α through NLRP3-GSDMD/GSDME activation.
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Osteogénesis , Factor de Necrosis Tumoral alfa , Diferenciación Celular , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteoblastos/metabolismo , Piroptosis , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , RatonesRESUMEN
Spinal cord injury (SCI) is a destructive neurological disorder that causes impaired mobility, sensory, and autonomic dysfunctions. The loss of oligodendrocyte progenitor cells (OPCs), which can differentiate into mature oligodendrocytes and re-myelinate damaged axons, is related to poorer recovery for SCI patients. However, inhibiting OPCs loss has always been a difficult problem to overcome. In this study, we demonstrated the anti-ferroptosis effects of quercetin as a mechanism in erastin-induced OPC ferroptosis. Quercetin ameliorated erastin-induced ferroptosis in OPCs, as indicated by decreased iron concentration, reactive oxygen species (ROS) production, and increased content of glutathione (GSH) as well as more normal mitochondria morphology. Compared with erastin-induced OPCs, the myelin basic protein (MBP)-positive myelin and NF200-positive axonal was remarkably increased in quercetin-treated OPCs. Furthermore, quercetin ameliorated the erastin-induced ferroptosis as well as the myelin and axon loss of OPCs by downregulating transferrin. Transfected OPCs with transferrin overexpression plasmids significantly abrogated the protective role of quercetin in OPC ferroptosis. Using ChIP-qPCR, a direct interaction of transferrin with its upstream gene Id2 was found. The overexpression of Id2 reversed the effect of quercetin on OPC ferroptosis. In vivo study found that quercetin greatly decreased the area of injury, and enhanced the BBB score after SCI. Furthermore, in the SCI model, quercetin significantly downregulated Id2 and transferrin expression, while significantly up-regulated GPX4 and PTGS2 expression. In conclusion, quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway. These findings highlight quercetin as an anti-ferroptosis agent for the treatment or prevention of spinal cord injury.
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Células Precursoras de Oligodendrocitos , Traumatismos de la Médula Espinal , Humanos , Vaina de Mielina/metabolismo , Células Precursoras de Oligodendrocitos/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Transferrina/metabolismo , FerroptosisRESUMEN
BACKGROUND AND AIM: Traumatic spinal cord injury (SCI) is a common and devastating central nervous disease, the treatment of which faces many challenges to the medical community and society as a whole. Treatment measures based on oxidative stress of spinal motor neurons during SCI are expected to help restore biological functions of neurons under injury conditions. However, to date, there are no systematic reports regarding oxidative stress on spinal motor neuron injury. Our aim is to better understand and explain the influences and mechanisms of oxidative stress on spinal motor neurons during SCI. METHODS: We first exposed VSC4.1 motor neurons to hydrogen peroxide (H2 O2 ) and evaluated the effects on cell viability, morphology, cycling, and apoptosis, with an emphasis on the changes to the cytoskeleton and the effect of N-acetyl-l-cysteine (NAC) on these changes. Then, we investigated the effects of NAC on these cytoskeletal changes in vitro and in vivo. RESULTS: We found that H2 O2 caused severe damage to the normal cytoskeleton, leading to a reduction in neurite length and number, rearrangement of the actin cytoskeleton, and disorder of the microtubules and neurofilaments in VSC4.1. Importantly, NAC attenuated the oxidative damage of spinal motor neurons in vitro and in vivo, promoting the recovery of hindlimb motor ability in mice with SCI at the early stage of injury. CONCLUSION: This study shows that oxidative stress plays an important role in the cytoskeleton destruction of spinal motor neurons in SCI, and treatment of SCI on this basis is a promising strategy. These findings will help to elucidate the role of oxidative stress in spinal motor neuron injury in SCI and provide references for further research into the study of the pathology and underlying mechanism of SCI.
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Neuronas Motoras , Traumatismos de la Médula Espinal , Ratones , Animales , Estrés Oxidativo , Traumatismos de la Médula Espinal/terapia , Citoesqueleto/patología , Microtúbulos/patología , Médula EspinalRESUMEN
OBJECTIVE: To probe the performance of miR-337-3p on the facet joint osteoarthritis (FJOA) and its underlying mechanism. METHODS: qRT-PCR and Western blot were utilized to analyze the levels of miR-337-3p and DUSP1 in the synovial tissues from 36 FJOA patients and 10 healthy controls. The human synovial fibroblasts of FJOA were isolated and cultured followed by cell transfection. Then, cells were exposed to 10 ng/mL of IL-1ß to induce inflammatory response of synovial fibroblasts. The alternation on cell biological function in cell models was determined. The binding of miR-337-3p and SKP2 was predicted by StarBase, TargetScan, DIANA-microT and miRmap, and further verified by RIP assay and dual-luciferase reporter assay. Co-IP experiment and ubiquitination assay were used to display the binding of SKP2 and DUSP1 as well as the ubiquitination and degradation of DUSP1. After that, the FJOA rat model was established and miR-337-3p mimic or negative control was given to rats by tail vein injection. The pathological changes of synovial tissues, synovitis score, and inflammation level in rats were assessed. RESULTS: The low expressions of miR-337-3p and DUSP1 were noticed in the synovial tissues of FJOA patients and in IL-1ß-induced synovial fibroblasts, and highly expressed p-p38 MAPK was noticed. Upregulation of miR-337-3p/DUSP1 or downregulation of SKP2 inhibited IL-1ß-induced proliferation and inflammatory response of synovial fibroblasts. SKP2 was the target gene of miR-337-3p, and SKP2 induced the ubiquitination and degradation of DUSP1. MiR-337-3p exerted a protective effect on FJOA rats by alleviating damage of rat synovial tissues, promoting cell apoptosis and repressing inflammatory response. CONCLUSION: MiR-337-3p plays a protective role in FJOA by negatively targeting SKP2 to suppress DUSP1 ubiquitination and inactivate the p38 MAPK pathway.
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MicroARNs , Osteoartritis , Articulación Cigapofisaria , Animales , Humanos , Ratas , Apoptosis/genética , Regulación hacia Abajo , Fosfatasa 1 de Especificidad Dual/genética , Fosfatasa 1 de Especificidad Dual/metabolismo , Inflamación/genética , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/patología , Articulación Cigapofisaria/metabolismo , Articulación Cigapofisaria/patologíaRESUMEN
Flexible transparent metal electrodes (FTMEs) have significant application potentials in the fields of flexible optoelectronic devices due to their outstanding optical transmittance and electrical conductivity. However, obtaining excellent optoelectrical properties and mechanical flexibility of FTMEs is challenging because ultrathin metal layers usually follow an island growth mode. In this paper, flexible transparent ultrathin Ag electrodes with high mechanical stability and good optoelectrical properties were exploited by tailoring the surface properties of plastic substrates with ultraviolet-ozone (UVO) treatment for regulating the nucleation and growth kinetics of Ag films. The composite transparent electrodes of Ag (9 nm)/MoO3 (20 nm) fabricated on the UVO-treated polyethylene terephthalate (PET) substrates possess a low sheet resistance of â¼7.9 Ω/sq, a high optical transmittance of â¼87.2% at 550 nm, a long-period environmental stability of 30 days (â¼65 °C, â¼80% humidity), and excellent mechanical flexibility of 100,000 bending cycles at a bending radius of 1.5 mm. These properties are derived from the surface treatment of PET substrates by UVO, which increases substrate surface energy and produces chemical nucleation sites of the phenolic hydroxyl groups. The phenolic hydroxyl groups generated on the PET surface not only provided efficient nucleation sites for subsequent Ag film growth but also formed C-O-Ag bonds between the substrate surface and the Ag layer, which act as "anchor chains" to fix firmly the Ag atoms on the substrate surface. As a universal applicability strategy, the composite electrodes on the UVO-treated polyethylene naphthalate (PEN) and norland optical adhesive 63 (NOA63) substrates also possess excellent optoelectrical properties and mechanical flexibility. Based on the ultrathin Ag composite electrodes, the flexible white organic light-emitting devices with PET, PEN, and NOA63 as substrates present the maximum current efficiencies of 53.0, 77.0, and 65.2 cd/A, respectively.
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BACKGROUND: Our previous study identified miR-99a as a negative regulator of early chondrogenic differentiation. However, the functional role of miR-99a in the pathogenesis of osteoarthritis (OA) remains unclear. METHODS: We examined the levels of miR-99a and Frizzled 8 (FZD8) expression in tissue specimens. Human SW1353 chondrosarcoma cells were stimulated with IL-6 and TNF-α to construct an in vitro OA environment. A luciferase reporter assay was performed to analyze the relationship between miR-99a and FZD8. CCK-8 assays, flow cytometry, and ELISA assays were used to assess cell viability, apoptosis, and inflammatory molecule expression, respectively. Percutaneous intra-spinal injections of papain mixed solution were performed to create an OA Sprague-Dawley rat model. Alcian Blue staining, Safranin O Fast Green staining, and Toluidine Blue O staining were performed to detect the degrees of cartilage injury. RESULTS: MiR-99a expression was downregulated in the severe spine OA patients when compared with the mild spine OA patients, and was also decreased in the experimentally induced in vitro OA environment when compared with the control environment. Functionally, overexpression of miR-99a significantly suppressed cell apoptosis and extracellular matrix degradation stimulated by IL-6 and TNF-α. FZD8 was identified as a target gene of miR-99a. Furthermore, the suppressive effects of miR-99a on cell injury induced by IL-6 and TNF-α were reversed by FZD8 overexpression. Moreover, the levels of miR-99a expression were also reduced in the induced OA model rats, and miR-99a agomir injection relieved the cartilage damage. At the molecular level, miR-99a overexpression downregulated the levels of MMP13, ß-catenin, Bax, and caspase-3 protein expression and upregulated the levels of COL2A1 and Bcl-2 protein expression in the in vitro OA-like chondrocyte model and also in the experimental OA model rats. CONCLUSIONS: Our data showed that miR-99a alleviated apoptosis and extracellular matrix degradation by targeting FZD8, and thereby suppressed the development and progression of experimentally induced spine osteoarthritis.
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MicroARNs , Osteoartritis de la Columna Vertebral , Osteoartritis , Receptores de Superficie Celular , Animales , Apoptosis/genética , Caspasa 3/metabolismo , Matriz Extracelular/patología , Humanos , Interleucina-6/metabolismo , Luciferasas/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/patología , Osteoartritis de la Columna Vertebral/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/metabolismo , beta Catenina/metabolismoRESUMEN
Aims: As one of the most prevalent malignant diseases in the world, the mechanisms of metastasis in colon cancer are poorly understood. The aim of this study was to investigate the role of the HGF/c-MET axis in the proliferation and metastasis in colon cancer. Methods: The effect of MACC1 on cell proliferation and metastasis was analyzed through a series of in vitro experiments. The role of MACC1 in cancer cells was demonstrated by overexpression and silencing of MACC1 in gain or loss function experiments. To investigate the relationship between MACC1 and c-MET/HGF, we detected c-MET protein expression by disrupting with or overexpressing MACC1. The bioinformatics analysis was used to investigate the correlation between MACC1 and c-MET, and the c-MET expression after the interference of HGF with MACC1 was determined. Subsequently, the function of c-MET was verified in colon cancer cells by a series of experiments. The mouse tumor transplantation model experiment is most suitable in vivo. Results: The results indicated that the overexpression of MACC1 could accelerate proliferation and facilitate metastasis in colon cancer cell lines. Furthermore, c-MET was determined to be the downstream regulator of MACC1. The addition of HGF could stimulate the expression of MACC1. With further exploration, we proved that c-MET is downstream of MACC1 in colon cancer and that overexpression of c-MET in colon cancer enhances cell proliferation and migration capability. At last, MACC1 expression level negatively correlates with the infiltration levels and several immune checkpoint biomarkers. High MACC1 expression has a lower response rate with ICIs in COAD. Conclusions: We found that, under the regulation of the MACC1/HGF/c-MET axis, the proliferation and metastasis of colorectal cancer are increased by MACC1, which can be a novel biomarker for predicting ICIs response in colorectal cancer. Our findings provide a new idea for the targeted treatment of colorectal cancer.
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Triple negative breast cancer (TNBC) is a greatly aggressive subtype of breast cancer with high recurrence and mortality rates. Chemotherapy as a primary treatment for cancer is limited due to toxic side effects and drug resistance. Therefore, low toxicity and more effective breast cancer therapeutic approaches are greatly desired. In this study, a strategy which using ZIF-90 nanoparticles co-deliver Ce6-anti-miR-21 and Ce6-anti-miR-155 into the tumor cells was developed. Due to the pH responsive drug release of ZIF-90, antisense oligonucleotides (anti-miRNAs) and photosensitizers are able to be efficiently released inside tumor microenvironment. The nano delivery system captures overexpressed oncogenic miRNAs while the photosensitizer Ce6 generates ROS under light irradiation to effectively induce the apoptosis of tumor cell. This combinatorial effect was verified by results showing that the purposed therapic method could effectively inhibit tumor cell proliferation and metastasis. The concept of antisense oligonucleotide combined with photodynamic therapy has great potential in cancer treatment or adjuvant therapy.
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MicroARNs , Oligonucleótidos Antisentido , Fotoquimioterapia , Fármacos Fotosensibilizantes , Neoplasias de la Mama Triple Negativas , Humanos , Línea Celular , Proliferación Celular/efectos de los fármacos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , MicroARNs/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas , Metástasis de la Neoplasia , Oligonucleótidos Antisentido/farmacología , Tamaño de la Partícula , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Propiedades de Superficie , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
The South American tomato pinworm, Tuta absoluta, is one of the most destructive insect pests in Solanaceae crops, particularly in tomatoes. Current methods of management have proven somewhat effective but still require a more efficacious management strategy to limit its havoc on crop yield. Tomato is much more predisposed to T. absoluta as compared with other plants such as eggplants, but the underlying causes have not been fully determined. We conducted this study to unravel the volatile organic compounds (VOCs) and primary/secondary metabolites that account for the differential response of tomatoes and eggplants to T. absoluta infestation. We performed widely targeted comparative metabolome and volatilome profiling by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME/GC-MS), respectively, on eggplants and tomatoes under control and T. absoluta infestation conditions. Overall, 141 VOCs and 797 primary/secondary metabolites were identified, largely dominated by aldehyde, alcohols, alkanes, amine, aromatics, a heterocyclic compound, ketone, olefin, phenol, and terpenes. Most of the VOCs and primary/secondary metabolites from the terpene class were largely differentially regulated in eggplants compared with tomatoes. Eggplants emitted several compounds that were lower or completely absent in tomatoes either under control conditions or after T. absoluta infestation. The results from an electroantennogram showed that 35 differentially accumulated VOCs could elicit female T. absoluta response, implying that these volatile compounds significantly alter the behavior of this pest. These findings demonstrated that differentially accumulated metabolites and volatile compounds play major roles in eggplant resistance to T. absoluta infestation as these compounds were regulated upon attack by T. absoluta. Our findings can assist in integrated pest management efforts by developing appropriate control measures against T. absoluta in Solanaceae production.
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Quercetin (Que), one of the flavonoids, exerts numerous actions on the central nervous system. However, the roles and underlying mechanism of Que in locomotor function recovery and axonal regeneration following spinal cord injury (SCI) have not been fully elucidated. A rat model of spinal cord injury (SCI) was established at T10 using the modified Allen's method. The results in our study indicated that Basso, Beattie and Bresnahan (BBB) locomotor scores were significantly higher after Que treatment. Additionally, Que administration cut down the latency of somatosensory evoked potentials (SEP) and motor evoked potentials (MEP), increased the amplitude of MEP and SEP following SCI. Hematoxylin-eosin (HE) staining demonstrated that Que administration reduced lesion size and cavity formation. Biotinylated dextran amine (BDA) anterograde tracing revealed that BDA positive fibres were increased by Que following SCI. Immunofluorescence staining revealed that Que elevated 5-hydroxytryptamine (5-HT) positive nerve fibres and neurofilament-200 (NF-200) positive neurons, reduced glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, Que inhibited GFAP expression, increased both NeuN and NF-200 expression and facilitated the spinal cord energy metabolism. Moreover, Que increased 18 F-FDG uptake in a time-dependent manner. Furthermore, Que increased Beclin 1 and LC3 II expression, blocked the phosphorylation of Akt, mTOR and p70S6K. 3-methyladenine (3-MA) partly abolished the neuro-protective roles of Que following SCI. Taken together, our study suggested that Que might promote locomotor function recovery, axonal regeneration and energy metabolism through induction of autophagy via Akt/mTOR/p70S6K pathway.
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Recuperación de la FunciónRESUMEN
BACKGROUND: Total arterial revascularization is associated with increased patency and long-term efficacy and decreased perioperative morbidity and mortality and incidence of cardiac-related events and sternal wound infection compared with conventional coronary artery bypass surgery (CABG), in which the left internal mammary artery (LIMA) is typically grafted to the left anterior descending artery with additional saphenous vein grafts often used. This study determined whether these favorable clinical results could be realized at the authors' institute. AIM: To summarize the early efficacy and clinical experience of individualized total arterial coronary artery bypass grafting surgery. METHODS: CABG was performed on 35 patients with non-single-vessel coronary artery disease by adopting total arterial grafts at Fourth Affiliated Hospital of Harbin Medical University between April 2016 and December 2019. LIMA was used in 35 patients, radial artery (RA) was used in 35 patients, and right gastroepiploic artery (RGEA) was used in 9 patients. Perioperative complications were observed, short-term graft patency rate was followed-up, and quality of life was assessed. RESULTS: All patients underwent off-pump coronary artery bypass and the surgeries were successful. All of them were discharged without any complications or deaths. During the follow-up, it was found that patients' angina symptoms were relieved and New York Heart Association classification for cardiac function was class I to class II. A total of 90 vessels were grafted with no occlusion for internal mammary artery, three occlusions for RA, and one occlusion for RGEA. CONCLUSION: The individualized total arterial strategy based on the vessels targeting individual anatomic characteristics can achieve complete revascularization with satisfactory short-term grafting patency rate.
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INTRODUCTION: Quercetin was recently reported to help protect against osteoarthritis (OA) progression, but the molecular mechanism for that protective affect remains unclear. METHODS: Here, OA model rats were intraperitoneally injected with quercetin, and the severity of cartilage damage in the rats was evaluated by H&E, Safranin O, and Toluidine blue, as well as by using the Osteoarthritis Research Society International (OARSI) Scoring System. Additionally, rat chondrocytes were treated with quercetin and then stimulated with IL-1ß. The levels of pro-inflammatory cytokines (IL-1ß, IL-18, and TNF-α) were detected by ELISA.Cell apoptosis was evaluated by flow cytometry and Hoechst staining. ROS levels were measured using a DCFH-DA probe. Protein expression was evaluated by Western blotting, immunohistochemical staining, and immunofluorescence. RESULTS: Our data showed that quercetin attenuated the degeneration and erosion of articular cartilage, suppressed inflammation and apoptosis, and downregulated the levels of IRAK1, NLRP3, and caspase-3 expression. In vitro data showed that overexpression of NLRP3 could reverse the suppressive effect of quercetin on IL-1ß-induced rat chondrocyte injuries. Importantly, rescue experiments confirmed that quercetin inhibited IL-1ß-induced rat chondrocyte injuries in vitro by suppressing the IRAK1/NLRP3 signaling pathway. CONCLUSION: Our study indicated that quercetin inhibits IL-1ß-induced inflammation and cartilage degradation by suppressing the IRAK1/NLRP3 signaling pathway.