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BACKGROUND: To evaluate the effect of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) on female sexual function. METHODS: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2100050887, 07/09/2021). In this prospective cohort study, we prospectively analyzed the data of the female sexual function index (FSFI) questionnaire of 130 patients who underwent laparoscopy in Chengdu Women's and Children's Central Hospital due to gynecological benign diseases. The patients were assigned to the vNOTES group and the control group (underwent traditional laparoscopic surgery or transumbilical laparoendoscopic single-site surgery). RESULTS: There were 4 cases dropout in the vNOTES group and 2 cases dropout in the control group. There was no difference in the ages (31.70 ± 5.02 vs. 30.37 ± 5.74, P>0.05), BMI (body mass index, 21.76 ± 3.16 vs. 23.30 ± 2.69, P>0.05), Education level, surgical types, and FSFI scores (22.31 ± 2.25 vs. 21.55 ± 3.38) between the vNOTES group and the control group before surgery. There was no difference in FSFI scores six months postoperation between the vNOTES group and the control group (21.61 ± 3.22 vs. 20.99 ± 3.26, P>0.05), and there was no difference in FSFI scores pre- and six months postoperation in vNOTES group (21.61 ± 3.22 vs. 22.31 ± 2.25, P>0.05). The time to start sexual life after surgery in the vNOTES group was later than that in the control group (39.34 ± 0.71 d versus 37.86 ± 0.69 d, P < 0.05). CONCLUSIONS: vNOTES has no significant adverse effect on female sexual function, however, the time to start sexual life after vNOTES is later than that after trans-abdominal laparoscopy.
Assuntos
Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Feminino , Humanos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Estudos Prospectivos , Inquéritos e Questionários , Vagina/cirurgia , AdultoRESUMO
Bright-field imaging and edge imaging can extract different characteristics from objects, and therefore play important roles in image processing and pattern recognition. Here, we propose a fast, convenient, and electrically driven adjustable scheme to achieve tunable edge-enhanced images based on computing metasurfaces. The computing metasurface can perform spatial differential operation as optical waves propagate through it. This optical differential operation is polarization-dependent, thus any desirable contrast can be realized by the interplay between two orthogonal polarization components. By regulating the external voltages applied on the liquid-crystal phase plate, different phase retardances between two orthogonal polarization components are introduced; this allows us to quickly switch between the bright-field image and the edge image.
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Nur77, an orphan nuclear receptor, is implicated in regulating diverse cellular biological processes including apoptosis and inflammation. We previously identified BI1071 (DIM-C-pPhCF3+MeSO3-), an oxidized methanesulfonate salt of (4-CF3-Ph-C-DIM), was a direct ligand of Nur77, which could activate the Nur77-Bcl-2 apoptotic pathway. To obtain more effective compounds targeting the Nur77-mediated apoptotic pathway, we designed and synthesized a series of BI1071 analogs by introducing various substituent groups in the indolyl-rings of BI1071. Structure-activity relationship study identified A11, B5 and B15 as improved analogs with stronger binding affinity to Nur77 and enhanced apoptotic activity compared to BI1071. Nur77-binding studies demonstrated that A11, B5 and B15 bind to Nur77 with a Kd of 34 nM, 19 nM and 16 nM, respectively. Furthermore, mechanism studies showed that A11, B5 and B15 induced apoptosis through utilizing the Nur77-Bcl-2 pathway.
Assuntos
Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Ligação Proteica , Estresse OxidativoRESUMO
Optical analog computing has attracted widespread attention in recent decades due to its advantages of lower consumption, higher efficiency, and real-time imaging in image processing. Here, we propose a two-dimensional optical analog computing scheme based on the Brewster effect. We experimentally demonstrate two-dimensional edge detection with high efficiency. By combining microscopy, our approach may develop some significant applications in cellular and molecular imaging.
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Previously we identified the first retinoid X receptor-alpha (RXRα) modulators that regulate the RXRα biological function via binding to the coregulator-binding site. Here we report the characterization of the interactions between the hit molecule and RXRα through computational modeling, mutagenesis, SAR and biological evaluation. In addition, we reported studies of additional new compounds and identified a molecule that mediated the NF-κB pathway by inhibiting the TNFα-induced IκBα degradation and p65 nuclear translocation.
Assuntos
Receptor X Retinoide alfa/metabolismo , Tretinoína/síntese química , Benzopiranos/síntese química , Benzopiranos/química , Benzopiranos/metabolismo , Sítios de Ligação , Células HEK293 , Humanos , Ligantes , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , NF-kappa B/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Receptor X Retinoide alfa/antagonistas & inibidores , Receptor X Retinoide alfa/genética , Transdução de Sinais , Relação Estrutura-Atividade , Tretinoína/química , Tretinoína/metabolismoRESUMO
Nur77 (also called TR3 or NGFI-B), an orphan member of the nuclear receptor superfamily, induces apoptosis by translocating to mitochondria where it interacts with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic molecule. Nur77 posttranslational modification such as phosphorylation has been shown to induce Nur77 translocation from the nucleus to mitochondria. However, small molecules that can bind directly to Nur77 to trigger its mitochondrial localization and Bcl-2 interaction remain to be explored. Here, we report our identification and characterization of DIM-C-pPhCF3 +MeSO3 - (BI1071), an oxidized product derived from indole-3-carbinol metabolite, as a modulator of the Nur77-Bcl-2 apoptotic pathway. BI1071 binds Nur77 with high affinity, promotes Nur77 mitochondrial targeting and interaction with Bcl-2, and effectively induces apoptosis of cancer cells in a Nur77- and Bcl-2-dependent manner. Studies with animal model showed that BI1071 potently inhibited the growth of tumor cells in animals through its induction of apoptosis. Our results identify BI1071 as a novel Nur77-binding modulator of the Nur77-Bcl-2 apoptotic pathway, which may serve as a promising lead for treating cancers with overexpression of Bcl-2.