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Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.
Assuntos
Flavonoides , Sepse , Choque Séptico , Camundongos , Animais , Sirtuína 1/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Choque Séptico/tratamento farmacológico , Endotoxinas , Citocinas/metabolismo , Sepse/tratamento farmacológico , Anti-Inflamatórios/uso terapêuticoRESUMO
In TNF signaling, ubiquitination of RIP1 functions as an early cell-death checkpoint, which prevents the spatial transition of the signaling complex from complex-I to death-inducing complex-II. Here, we report that ankyrin repeat domain 13a (ANKRD13a) acts as a novel component of complex-II to set a higher signal threshold for the cytotoxic potential of TNF. ANKRD13a deficiency is sufficient to turn the response to TNF from survival to death by promoting the formation of complex-II without affecting NF-κB activation. ANKRD13a binds to ubiquitinated-RIP1 via its UIM, and subsequently limits the association of FADD and caspase-8 with RIP1. Moreover, high ANKRD13a expression is inversely correlated with apoptotic phenotypes in ovarian cancer tissues and is associated with poor prognosis. Our work identifies ANKRD13a as a novel gatekeeper of the early cell-death checkpoint, which may function as part of an escape mechanism from cell death in some cancers.
Assuntos
Proteínas de Membrana , NF-kappa B , Complexo de Proteínas Formadoras de Poros Nucleares , Neoplasias Ovarianas , Proteínas de Ligação a RNA , Fator de Necrose Tumoral alfa , Apoptose/fisiologia , Caspase 8/metabolismo , Morte Celular/fisiologia , Proteína de Domínio de Morte Associada a Fas/metabolismo , Feminino , Humanos , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , UbiquitinaçãoRESUMO
Freezing extends the shelf-life of food by slowing down the physical and biochemical reactions; however, ice crystal formation can result in irreversible damage to the cell's structure and texture. Supercooling technology has the potential to preserve the original freshness of food without freezing damage. In this study, fresh asparagus was preserved in a supercooled state and its quality changes such as color, weight loss, texture, chlorophyll and anthocyanin content, and enzymatic activities (superoxide dismutase and catalase) were evaluated. The asparagus samples were successfully supercooled at -3 °C with the combination treatment of pulsed electric field (PEF) and oscillating magnetic field (OMF), and the supercooled state was maintained for up to 14 days. Asparagus spears preserved in the supercooled state exhibited lower weight loss and higher levels of quality factors in comparison to the frozen and refrigerated control samples.
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BACKGROUND: Although the loop electrosurgical excision procedure (LEEP) is a brief procedure, it can cause severe pain and discomfort to patients in the absence of adequate sedation. An admixture of ketamine with propofol (ketofol), may reduce patient movement due to insufficient sedation while providing hemodynamic and respiratory stability. This study evaluated the ability of two ratios of a propofol-ketamine combination, compared with propofol alone, to reduce patient movement during procedural sedation for LEEPs. METHODS: One hundred and twenty women scheduled for a LEEP were randomly assigned to three groups. Anesthesia was induced with 1 mg/kg propofol (group P), 1 mg/kg propofol and 0.33 mg/kg ketamine (group K1), or 1 mg/kg propofol and 0.66 mg/kg ketamine (group K2). The primary outcome was the incidence of adduction motion in the lower extremities during the procedure. The requirements for respiratory interventions, changes in vital signs, sedation score, additional anesthetic usage, and surgeon and patient satisfaction were also evaluated. RESULTS: The incidence of adduction motion was significantly lower in groups K1 and K2 than in group P (overall p-value <0.001) but did not differ significantly in groups K1 and K2. Group K2 needed more jaw thrust maneuvers than group K1. Additional propofol usage was lower and surgeon satisfaction scores higher in groups K1 and K2 than in group P. CONCLUSION: A propofol-ketamine combination is more effective than propofol alone in reducing procedural interference during LEEPs. However, increasing the dose of ketamine showed no additional benefit.
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Lateral facial cleft is a rare congenital anomaly, but all affected infants require surgery under general anesthesia. Conventional 2-dimensional coronal view of the face, which is typically used for identification of facial clefts, has limitations with regard to detection of this anomaly. We describe a case of prenatal diagnosis of isolated lateral facial cleft made with 3D sonography and highlight the importance of this tool in the diagnosis of this rare facial deformity.
Assuntos
Fenda Labial/diagnóstico por imagem , Imageamento Tridimensional , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Humanos , GravidezRESUMO
Uterine scar dehiscence following laparoscopic myomectomy rarely occurs but can compromise both maternal and fetal well-being in subsequent pregnancy. We here present two cases of pregnancy complicated by preterm birth that resulted from uterine scar dehiscence following laparoscopic myomectomy. First case was a nulligravida who had scar dehiscence at 26 weeks of gestation after having a laparoscopic myomectomy 3 months prior to conception. Two weeks later, we observed her fetal leg protruding through the defect. The other case was a primigravida with a history of prior cesarean delivery, whose sonography revealed myomectomy scar dehiscence at 31 weeks of gestation. Within a few hours after observing, the patient complained of abdominal pain that was aggravating as fetal leg protruded through the defect. In both cases, babies were born by emergency cesarean section. Conservative management can be one of treatment options for myomectomy scar dehiscence in preterm pregnancy. However, clinicians should always be aware of the possibility of obstetric emergencies.
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OBJECTIVE: This study was conducted to compare the surgical outcomes between two-port access and four-port access laparoscopic ovarian cystectomy. METHODS: Four hundred and eighty nine patients who had received two-port access laparoscopic ovarian cystectomy (n=175) and four-port access laparoscopic ovarian cystectomy (n=314) in Chungnam National University Hospital from January 2009 to August 2012 were analyzed retrospectively. The data were compared between the bilaterality of the cysts and cyst diameter of less than 6 cm and 6 cm or more. RESULTS: There were no significant differences in patient's age, parity, body weight, body mass index and history of previous surgery between the two-port and four-port access laparoscopy group. Bilaterality of ovarian cysts was more in fourport access laparoscopy group (13.7% vs. 32.5%, P=0.000). There were no significant differences in operation time, hemoglobin change, hospital stay, adhesiolysis, transfusion, and insertion of hemo-vac between the two-port and four-port access laparoscopy group for size matched compare. However additional analgesics were more in four-port access laparoscopy group for unilateral ovarian cystectomy. CONCLUSION: Two-port access laparoscopic surgery was feasible and safe for unilateral and bilateral ovarian cystectomy compare with four-port access laparoscopic surgery.
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OBJECTIVE: The purpose of this study was to evaluate postoperative prognosis and progression in patients who received laparoscopic-assisted adenomyomectomy using the double flap method. METHODS: The pelvic cavity was explored by the conventional laparoscopic method, and drainage was achieved through a 5-mm trocar. After a small incision in the abdomen, the uterus was incised from the fundus to the upper cervical margin until exposing the endometrial cavity. Adenomyotic tissue was removed using a scalpel, scissors, or monopolar electrical bovie. The endometrial cavity was repaired with interrupted sutures using 2-0 vicryl. One side of the serosal flap was used to cover the endometrial side of the uterus. The second serosal flap covered the first flap after removal of the serosal surface of the first flap. RESULTS: From January 2008 to March 2012, there were 11 cases of laparoscopic-assisted adenomyomectomy at Chungnam National University Hospital. Nine cases were analyzed, excluding two cases with less than one year of follow-up. The average patient age was 37.0 years and average follow-up duration was 32.8 months. All patients showed improvement in dysmenorrhea (P < 0.001) and hypermenorrhea (P = 0.001) after surgery and were evaluated by visual analogue scale score. However, symptoms of adenomyosis were aggravated in three patients. Adenomyosis was progressed in the side opposite the site of operation. One patient required a total laparoscopic hysterectomy 27 months after surgery. CONCLUSION: Laparoscopic-assisted adenomyomectomy using the double flap method is effective for uterine reduction and relief of dysmenorrhea and hypermenorrhea. Conservative management and careful follow-up are needed because adenomyosis can recur or progress in some patients.
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Herein, we describe a novel multiplex genotyping method, GTPlex-PyroSeq. This method consists of two phases: multiplex PCR followed by a single reaction of pyrosequencing. This study demonstrates how GTPlex-PyroSeq can be adapted for the determination of multiple human papillomavirus (HPV) genotypes. A biotinylated consensus primer, GP6+, and 15 high-risk HPV type-specific primers are used for multiplex PCR. Each type-specific primer has a 5'-tag unique ID sequence connected to a pyrosequencing primer binding region. The unique ID sequence is composed of three parts: i) a single nucleotide ID representing a specific genotype; ii) a sign post; and iii) an end mark. This design allows multiple genotype determination under an ID sequence-dependent nucleotide dispensation order during pyrosequencing. Following initial studies using HPV plasmids and cell lines, we evaluated the clinical utility and effectiveness by comparing our assay with direct sequencing and HPV DNA chip analysis of 80 samples from high-risk, HPV-positive patients. We found in single-type infections, 100% concordance with direct sequencing (70 of 80 perfect matches) and 97.5% concordance with HPV DNA chip data (50 of 80 perfect matches). Additionally, our system was superior to direct sequencing in detection of multiple infections (12 of 80), with a limit of detection of 100 copies. The scalability of this multiplex system, with its open-platform design and ability to use various sample types, makes the GTPlex applicable for use in multiple settings.