RESUMEN
Multidrug-resistant Edwardsiella tarda threatens both sustainable aquaculture and human health, but the control measure is still lacking. In this study, we adopted functional proteomics to investigate the molecular mechanism underlying norfloxacin (NOR) resistance in E. tarda. We found that E. tarda had a global proteomic shift upon acquisition of NOR resistance, featured with increased expression of siderophore biosynthesis and Fe3+-hydroxamate transport. Thus, either inhibition of siderophore biosynthesis with salicyl-AMS or treatment with another antibiotic, kitasamycin (Kit), which was uptake through Fe3+-hydroxamate transport, enhanced NOR killing of NOR-resistant E. tarda both in vivo and in vitro. Moreover, the combination of NOR, salicyl-AMS, and Kit had the highest efficacy in promoting the killing effects of NOR than any drug alone. Such synergistic effect not only confirmed in vitro and in vivo bacterial killing assays but also applicable to other clinic E. tarda isolates. Thus, our data suggest a proteomic-based approach to identify potential targets to enhance antibiotic killing and propose an alternative way to control infection of multidrug-resistant E. tarda.
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Enfermedades de los Peces , Norfloxacino , Humanos , Animales , Norfloxacino/farmacología , Norfloxacino/metabolismo , Edwardsiella tarda/metabolismo , Proteómica , Sideróforos/metabolismo , Antibacterianos/farmacología , Enfermedades de los Peces/microbiologíaRESUMEN
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI. METHODS: SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett's T3 test (for unequal homogeneity) were used for statistical tests. RESULTS: ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed. CONCLUSION: Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model. Video Abstract.
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Neuroblastoma , Oxígeno , Humanos , Oxígeno/metabolismo , Quinasas MAP Reguladas por Señal Extracelular , Apoptosis , Glucosa/metabolismo , Dinaminas , AutofagiaRESUMEN
Edwardsiella tarda represents one of the most important pathogens that infects a variety of hosts including aquatic animals and humans. The outbreak of E. tarda infection is frequently reported in aquaculture that causes huge economic loss. Due to the widespread of antibiotic resistance, available antibiotics to treat bacterial infection are limited. Therefore, enhancing aquatic animals to survive upon E. tarda infection become an urgent issue. In this study, we profiled the metabolomic change of tilapia in-between the dying and survival fish upon E. tarda infection. The dying and survival fish mounts differential metabolic response, from which we identify a key metabolite, taurine, whose abundance is increased in both the survival group and the dying group but is more significant in the survival group. Exogenous taurine increases tilapia survival rate by 37.5% upon E. tarda infection. Further quantitative PCR analysis demonstrate taurine increases the expression of immune genes in liver, spleen and head kidney. Therefore, our study shows a new strategy to enhance fish immune response against bacterial infection.
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Cíclidos , Infecciones por Enterobacteriaceae , Enfermedades de los Peces , Tilapia , Animales , Antibacterianos/metabolismo , Edwardsiella tarda/fisiología , Humanos , Taurina/metabolismo , Taurina/farmacologíaRESUMEN
Aromatic imide derivatives play a critical role in boosting the electroluminescent (EL) performance of organic light-emitting diodes (OLEDs). However, the majority of aromatic imide-based materials are limited to long wavelength emission OLEDs rather than blue emissions due to their strong electron-withdrawing characteristics. Herein, two novel polycyclic fused amide units were reported as electron acceptor to be combined with either a tetramethylcarbazole or acridine donor via a phenyl linker to generate four conventional fluorescence blue emitters of BBI-4MeCz, BBI-DMAC, BSQ-4MeCz and BSQ-DMAC for the first time. BSQ-4MeCz and BSQ-DMAC based on a BSQ unit exhibited higher thermal stability and photoluminescence quantum yields than BBI-4MeCz and BBI-DMAC based on a BBI unit due to their more planar acceptor structure. The intermolecular interactions that exist in the BSQ series materials effectively inhibit the molecular rotation and configuration relaxation, and thus allow for blue-shifted emissions. Blue OLED devices were constructed with the developed materials as emitters, and the effects of both the structure of the polycyclic fused amide acceptor and the electron donor on the EL performance were clarified. Consequently, a sky-blue OLED device based on BSQ-DMAC was created, with a high maximum external quantum efficiency of 4.94% and a maximum luminance of 7761 cd m-2.
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OBJECTIVE: To evaluate long-term outcomes and surgical essentials of channel repair in endoscopic transcorporeal discectomy for cervical disc herniation. METHODS: From October 2019 to March 2020, 24 patients with cervical disc herniation underwent channel repair after percutaneous full-endoscopic anterior transcorporeal cervical discectomy. Five interventions were performed at C3-C4, 11 were performed at C4-C5, and 8 were performed at C5-C6. Clinical outcomes were evaluated by Neck Disability Index, Japanese Orthopaedic Association, and visual analog scale scores. Radiologic changes were evaluated with intervertebral disc height and drilled vertebral height. RESULTS: All procedures were completed with a mean operating time of 86.40 ± 8.19 minutes. Swollen neck was observed in 5 patients, which resolved within 2 hours. At the final follow-up, Neck Disability Index, Japanese Orthopaedic Association, and visual analog scale scores were improved significantly compared with preoperative assessments (P < 0.05); intervertebral disc height was decreased significantly (P < 0.05); and loss of drilled vertebral height was not significant (P > 0.05). All 24 bony channels disappeared by 3 months postoperatively. No other complications were observed. CONCLUSIONS: Percutaneous full-endoscopic anterior transcorporeal cervical discectomy with channel repair offers a minimally invasive and effective treatment option for patients with cervical disc herniation. This technique demonstrates favorable clinical outcomes, including preservation of cervical spine mobility and minimal complications. Although there was a significant loss of intervertebral disc height, no vertebral collapse occurred. Strict adherence to surgical indications and precautions is crucial for successful outcomes. Further research and long-term studies are required to validate the efficacy and safety of this approach in a larger patient population.
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Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/complicaciones , Estudios de Seguimiento , Endoscopía/métodos , Discectomía , Cuello/cirugía , Discectomía Percutánea/métodos , Resultado del Tratamiento , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the clinical effect of pure titanium used for complete denture and removable partial denture. METHODS: Sixty edentulous patients were selected. Thirty patients in the test group for pure titanium denture and the other 30 in control for Co-Cr Alloy denture. RESULTS: No significant differences in clinical effect between dental casting pure titanium and casting Co-Cr alloy used for complete denture or removable partial denture. CONCLUSION: Due to the properties and biocompatibility, pure titanium can be used for denture base and frameworks of removable partial denture.
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Revestimiento para Colado Dental/química , Diseño de Dentadura , Dentadura Completa , Dentadura Parcial Removible , Titanio/química , Técnica de Colado Dental , Humanos , Estrés Mecánico , Propiedades de SuperficieRESUMEN
Three patients diagnosed with peri-implant disease after osseointegration exhibited soft tissue oedema and fistulae. Treatment options for controlling the fistulae were investigated. Free subepithelial connective tissue grafts (SCTGs) and microinvasive surgery were used to improve the soft tissue biotype of the patients with fistulae. After SCTG surgery, the fistulae disappeared. The clinical outcomes were stable and aesthetic outcomes were satisfactory after 3-5 years of follow-up. Based on this study, utilising SCTG to improve the tissue biotype may be an effective clinical approach for controlling fistulae occurring during peri-implant disease.
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Tejido Conectivo , Periimplantitis , Encía , HumanosRESUMEN
A 27-year-old patient with a history of maxillary anterior tooth trauma presented with a maxillary central diastema between tooth- and implant-supported prostheses that had been in use for 5 years. The all-ceramic crowns were placed in 2012 after rigorous occlusal adjustment. Evaluations were carried out at 0, 2, 3, 4 and 5 years post restoration. The central diastema between the natural teeth and the implant-supported prosthesis on teeth 11 and 12 was first observed 2 years after implantation. After 5 years, the distance was found to have increased, with anterior occlusion and esthetic changes having taken place. The following possible causes were discussed: occlusal problems, anterior traumatic effects, the possible impact of guided bone regeneration (GBR) on the adjacent natural teeth and natural movement. More predictive information should be given to patients with implant-supported prostheses and natural teeth so that they are fully informed of the impact of any necessary clinical compromise and are aware of the modifications that may occur to their natural dentition.