RESUMO
The assembly of pH-responsive DNA-based, phase-separated microdroplets (MDs) coacervates, consisting of frameworks composed of Y-shaped nucleic acid modules crosslinked by pH-responsive strands, are introduced. The phase-separated MDs reveal dynamic pH-stimulated switchable or oscillatory transient depletion and reformation. In one system, a photoisomerizable merocyanine/spiropyran photoacid is used for the light-induced pH switchable modulation of the reaction medium between the values pH = 6.0 - 4.4. The dynamic transient photochemically-induced switchable depletion/reformation of phase-separated MDs, follows the rhythm of pH changes in solution. In a second system, the Landolt oscillatory reaction mixture pH 7.5 â 4.2 â7.5 is applied to stimulate the oscillatory depletion/reformation of the MDs. The autonomous dynamic oscillation of the assembly/disassembly of the MDs follows the oscillating pH rhythm of the reaction medium.
RESUMO
Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO-) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO- level during DILI in vivo. Therefore, ONOO--activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO--responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO--mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and â¼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO- concentration changes in living cells. Importantly, in vivo fluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO- in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO- under different pathological conditions.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Corantes Fluorescentes , Animais , Camundongos , Corantes Fluorescentes/metabolismo , Ácido Peroxinitroso/metabolismo , Compostos de Bifenilo , Imagem Óptica , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagemRESUMO
PURPOSE: To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. METHODS: In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. RESULTS: Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. CONCLUSION: Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.
Assuntos
Parede Abdominal , Endometriose , Feminino , Humanos , Gravidez , Endometriose/cirurgia , Endometriose/patologia , Parede Abdominal/cirurgia , Parede Abdominal/patologia , Estudos Retrospectivos , Cesárea , Resultado do TratamentoRESUMO
Photoresponsive nucleic acids attract growing interest as functional constituents in materials science. Integration of photoisomerizable units into DNA strands provides an ideal handle for the reversible reconfiguration of nucleic acid architectures by light irradiation, triggering changes in the chemical and structural properties of the nanostructures that can be exploited in the development of photoresponsive functional devices such as machines, origami structures and ion channels, as well as environmentally adaptable 'smart' materials including nanoparticle aggregates and hydrogels. Moreover, photoresponsive DNA components allow control over the composition of dynamic supramolecular ensembles that mimic native networks. Beyond this, the modification of nucleic acids with photosensitizer functionality enables these biopolymers to act as scaffolds for spatial organization of electron transfer reactions mimicking natural photosynthesis. This review provides a comprehensive overview of these exciting developments in the design of photoresponsive DNA materials, and showcases a range of applications in catalysis, sensing and drug delivery/release. The key challenges facing the development of the field in the coming years are addressed, and exciting emergent research directions are identified.
Assuntos
Nanopartículas , Nanoestruturas , Catálise , DNA , Sistemas de Liberação de MedicamentosRESUMO
Light offers unique opportunities for controlling the activity of materials and biosystems with high spatiotemporal resolution. Molecular photoswitches are chromophores that undergo reversible isomerization between different states upon irradiation with light, allowing a convenient means to control their influence over the system of interest. However, a significant limitation of classical photoswitches is the requirement to initiate the switching in one or both directions using deleterious UV light with poor tissue penetration. Red-shifted photoswitches are hence in high demand and have attracted keen recent research interest. In this Review, we highlight recent progress towards the development of visible- and NIR-activated photoswitches characterized by distinct photochromic reaction mechanisms. We hope to inspire further endeavors in this field, allowing the full potential of these tools in biotechnology and materials chemistry applications to be realized.
Assuntos
Raios UltravioletaRESUMO
BACKGROUND AND OBJECTIVES: The application of pure natural orifice translumenal endoscopic surgery (NOTES) to intra-abdominal visceral resections remains limited due to the complexity of the dissection. This study aimed to assess the safety and feasibility of laparoscopic right colectomy using a purely transvaginal approach. METHODS: The data of 12 continuous patients with colon neoplasia who underwent transvaginal right colectomy from November 2018 to July 2020 were prospectively collected, and their perioperative events were recorded. RESULTS: The patients' median age was 70.4 years. Four were diagnosed with colon adenoma and eight with adenocarcinoma. The median operative time was 185 min, with a median blood loss of 25 ml. The median time to gas passing was 32.5 h after surgery. The median postoperative hospital stay was 6 days. One operation was converted to hybrid NOTES due to difficulty with the anastomosis, and one was converted to laparoscopic surgery because of vascular injury. Three cases were grades I, II, and III according to the Clavien-Dindo classification. CONCLUSION: Pure NOTES right colectomy using the transvaginal approach is feasible and safe with good short-term outcomes. We recommend this novel technique for highly-selected patients with no more than a D2 dissection performed by experienced colorectal surgeons.
Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenoma/patologia , Adenoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Vagina/cirurgiaRESUMO
BACKGROUND: Adenomyosis (AM) and endometriosis (EM) often coexist. Laparoscopic surgery is one of the main methods for diagnosing and treating these conditions. This study aims to investigate the pregnancy outcomes of women with infertility with both AM and EM after laparoscopic surgery and to identify the relevant associated factors. METHODS: This is a retrospective study involving women with infertility diagnosed with EM and AM. All patients had undergone laparoscopic surgery and were divided into two groups according to their pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected. RESULTS: A total of 226 female patients with infertility diagnosed with both AM and EM underwent laparoscopic surgery. Of these, a total of 176 patients completed follow-up. Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The clinical pregnancy and live birth rates were 67.4 and 55.11%, respectively. One hundred thirty-five patients received in vitro fertilization (IVF), with 70 (51.85%) of these patients having live births. Age, endometrioma size, and uterus size were significantly lower in those who had a successful delivery. There was no statistically significant difference in symptoms, except that those who achieved live birth had a lower rate of anaemia (13.40% vs. 25.32%, p = 0.044). The group that did not proceed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (p < 0.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR: 1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live birth in the multivariable analysis. CONCLUSIONS: Endometriosis and adenomyosis appear to have an adverse effect on pregnancy outcome. These might be related to the size of the uterus and EFI. Obstetricians and gynaecologists should be alert to this potential adverse effect and manage these patients accordingly.
Assuntos
Adenomiose/cirurgia , Endometriose/cirurgia , Laparoscopia , Nascido Vivo , Adulto , China/epidemiologia , Feminino , Seguimentos , Humanos , Infertilidade , Gravidez , Resultado da Gravidez/epidemiologia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Although transvaginal natural orifice transluminal endoscopic surgery (NOTES) is gaining importance, knowledge on transvaginal NOTES procedures in gynecologic practice is limited. OBJECTIVE: We aimed at evaluating the feasibility and safety of performing hysterectomy and bilateral adnexectomy (or bilateral salpingectomy) via transvaginal NOTES using a self-developed multichannel abdominal port and vaginal support ring. STUDY DESIGN: A prospective, single-center, cohort pilot study was conducted from May to December 2017 in patients with benign uterine diseases or endometrial atypical hyperplasia or cervical intraepithelial neoplasia (n = 30) scheduled for laparoscopic hysterectomy. The procedure was performed using a self-developed five-channel port and a vaginal support ring. RESULTS: Hysterectomy and bilateral adnexectomy (or bilateral salpingectomy) in all 30 cases (mean age: 51.43 ± 4.60 years and body mass index: 23.42 ± 1.45 kg/m2 ) were successfully performed completely under transvaginal NOTES. Mean operation time was 95.90 ± 14.60 minutes and mean blood loss during the procedure was 52.50 ± 19.20 mL. Average weight of specimen was 79.97 ± 35.48 g. Only one complication of bladder injury was noted and was rectified accordingly. Visual Analog Score (VAS) at first day after operation was 2.70 ± 0.72. After follow-up for 4.50 ± 1.85 months, all the patients' vaginal stump healed well without scar formation. CONCLUSION: Our study showed that use of multichannel abdominal port could make laparoscopic instruments easier to fix and operate wherein the vaginal support ring reduces the leakage of carbon dioxide pneumoperitoneum. There was no scar on the abdomen and VAS was much lower. This study also demonstrated cosmetic benefits and rapid postoperative recovery.
Assuntos
Cirurgia Endoscópica por Orifício Natural , Neoplasias do Colo do Útero , Abdome , Feminino , Humanos , Histerectomia , Histerectomia Vaginal , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
Single-cell and inâ situ cell-based operation with nanopipette approach offers a possibility to elucidate the intracellular processes and may aid the improvement of therapy efficiency and precision. We present here a photo-responsive hydrogel-nanopipette hybrid system that can achieve single-cell operation with high spatial/temporal resolution and negligible cell damage. This strategy overcomes long-time obstacles in nanopipette single-cell studies as high electric potential (ca. 1000â mV) or organic solvent is always used during operations, which would inevitably impose disturbance and damage to targeted cells. The light-triggered system promotes a potential-free, non-invasive single-cell injection, resulting in a well-retained cell viability (90 % survival rate). Moreover, the photo-driven injection enables a precisely dose-controllable single-cell drug delivery. Significantly reduced lethal doses of doxorubicin (163-217â fg cell-1 ) are demonstrated in corresponding cell lines.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Injeções/instrumentação , Células A549 , Antineoplásicos/farmacologia , Sobrevivência Celular/fisiologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Hidrogéis/efeitos da radiação , LuzRESUMO
Here, we report a ß-galactosidase (ß-Gal)-responsive photochromic fluorescent probe, NpG, that was designed to prebind to human serum albumin (HSA) to form the probe/protein hybrid, NpG@HSA. The formation of NpG@HSA led to an increase in fluorescence emission (520 nm) corresponding to the binding of the fluorescent naphthalimide unit with HSA. In addition, this enabled visualization of the spiropyran fluorescence emission in aqueous media. Our probe/protein hybrid approach afforded a unique imaging platform with enhanced cell permeability and solubility that was capable of visualizing the cellular uptake of NpG@HSA before its activation by ß-Gal. The ß-Gal-mediated cleavage of the galactose unit within the NpG@HSA hybrid resulted in the formation of NpM@HSA and an increase in red fluorescence emission (620 nm). The resultant merocyanine unit was then able to undergo photoisomerization (merocyanine â spiropyran) to facilitate STORM (i.e., stochastic optical reconstruction microscopy) imaging with minimal phototoxicity and excellent photostability/reversibility. Using STORM, NpG@HSA was able to determine the subcellular distribution of ß-Gal activity between cell lines with nanoscale precision. We believe that this system represents a versatile imaging platform for the design of photochromic fluorescent probes suitable for illuminating the precise location of disease-specific biomarkers in various cellular processes.
Assuntos
Corantes Fluorescentes/química , beta-Galactosidase/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Linhagem Celular , Corantes Fluorescentes/síntese química , Humanos , Microscopia Confocal , Estrutura Molecular , Imagem Óptica , Processos Fotoquímicos , Albumina Sérica Humana/química , beta-Galactosidase/metabolismoRESUMO
Traditional biochemical methods for enzyme detection are mainly based on antibody-based immunoassays, which lack the ability to monitor the spatiotemporal distribution and, in particular, the in situ activity of enzymes in live cells and in vivo. In this review, we comprehensively summarize recent progress that has been made in the development of small-molecule as well as material-based fluorogenic probes for sensitive detection of the activities of enzymes that are related to a number of human diseases. The principles utilized to design these probes as well as their applications are reviewed. Specific attention is given to fluorogenic probes that have been developed for analysis of the activities of enzymes including oxidases and reductases, those that act on biomacromolecules including DNAs, proteins/peptides/amino acids, carbohydrates and lipids, and those that are responsible for translational modifications. We envision that this review will serve as an ideal reference for practitioners as well as beginners in relevant research fields.
Assuntos
Enzimas/química , Corantes Fluorescentes/química , Animais , Biomarcadores/metabolismo , Enzimas/metabolismo , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/enzimologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/enzimologia , Oxirredutases/química , Oxirredutases/metabolismo , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismoRESUMO
Objective: The surgical approach, hemostatic approach, histologic findings, and cyst size and location may have a role in reducing the ovarian reserve. The aim of this study was to investigate the impact of single-port laparoscopic cystectomy (SLC) and conventional laparoscopic cystectomy (CLC) on the ovarian reserve based on serum anti-Mullerian hormone (AMH) concentrations.Material and methods: This non-randomized concurrent control trial enrolled 79 female patients aged 18-45 years with benign ovarian cysts, including 47 patients in the SLC group and 32 patients in the CLC group. Outcome measures, including hospital stay, operative time, blood loss, analgesic use, body temperature, hospitalization cost, and serum AMH concentration, were evaluated preoperatively, two to three days postoperatively, and four to six weeks postoperatively.Results: The reduction in the AMH concentration after cystectomy was significantly different preoperatively, two to three days postoperatively (p < .001), and four weeks postoperatively (p < .001) regardless of the surgical approach (SLC or CLC) [F (1.00,31.00) = 0.026, p = .873]. Moreover, the hemostatic approach and histologic findings yielded significant differences in the serum AMH concentration regardless of the surgical approach (p < .05). The serum AMH concentration was higher in unilateral cysts (2.70 ± 1.80 ng/mL) than in bilateral cysts (1.73 ± 1.11 ng/mL) postoperatively (p < .05). In the SLC group, the serum AMH concentration in the patients with ovarian endometriomas (1.58 ± 1.39 ng/mL) was significantly lower than that in the patients with other cysts (3.22 ± 1.68 ng/mL) postoperatively (p < .05).Conclusion: The serum AMH concentration decreased over time postoperatively but did not significantly differ between SLC and CLC.
Assuntos
Cistectomia/métodos , Laparoscopia/métodos , Cistos Ovarianos/cirurgia , Reserva Ovariana , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Temperatura Corporal , Endometriose/sangue , Endometriose/etiologia , Endometriose/cirurgia , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune encephalitis mediated by anti-N-methyl-D-aspartate receptor antibodies. Ovarian teratoma is closely related to anti-N-methyl-D-aspartate receptor encephalitis. However, the optimal treatment remains unknown, and strategies used for the diagnosis and therapy, including surgical intervention of ovarian teratoma, are debatable. OBJECTIVE: The objective of the study was to study the clinical features of anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratoma to further understand the disease. STUDY DESIGN: This single-center prospective study included patients with anti-NMDAR encephalitis with ovarian teratoma from 2011 to 2016 who were admitted to Peking Union Medical College Hospital, Beijing, and discussed the clinical characteristics, treatment, and prognosis of the disease. The diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was established preoperatively by identifying anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid. Ovarian teratomas were suspected preoperatively by pelvic ultrasound and were diagnosed pathologically after laparoscopic detection and ovarian tumor resection. All patients were treated with first-line immunotherapy (steroids, intravenous immunoglobulin, and plasmapheresis), and when the therapy failed, they were treated with second-line immunotherapy (cyclophosphamide and rituximab). All patients were followed up regularly, and N-methyl-D-aspartate receptor antibodies, pelvic ultrasound, and neurological condition were monitored. Neurological symptoms were assessed using the modified Rankin Scale. RESULTS: A total of 108 female patients with anti-N-methyl-D-aspartate receptor encephalitis were screened, of whom, 29 patients (26.9% of 108; mean age ± SD, 23.14 ± 6.59 years) had pathologically confirmed ovarian teratoma. The incidence of fever, decreased consciousness, arrhythmia, central hypoventilation, ventilator-assisted respiration, and intensive unit care (75.9%, 65.5%, 27.6%, 55.2%, 55.2%, and 58.6%, respectively) were significantly higher in patients with ovarian teratoma than in those without ovarian teratoma. The modified Rankin Scale at the acute onset in those 29 patients was 4.11 ± 1.20, which was also much higher than that in patients without ovarian teratoma (3.58 ± 1.08). Of the 29 patients with ovarian teratoma, 22 (75.9%) underwent laparoscopy during the acute onset of neurological symptoms. The mean diameter of the tumor was 4.61 ± 3.41 cm (SD), and the smallest tumor was only 1 cm in the unilateral ovary. All other cysts, except 4 bilateral cysts (13.8%), were unilateral. Only 1 patient was diagnosed pathologically with immature ovarian teratoma, while others had benign ovarian teratomas. In all, 28 patients (96.5%) had a good outcome (modified Rankin Scale ≤2) and 1 died. In the follow-up visit (mean duration, 37.69 months), the relapse rate of encephalitis in patients with ovarian teratoma undergoing laparoscopic cystectomy was 14.6%, whereas for those without ovarian teratoma, the relapse rate was 33.3%. The removal of ovarian teratoma was associated with reduced risk of relapse. CONCLUSION: Patients having anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratomas tend to present more severe neurological conditions. The diameter of the tumor in these patients is not very large and could be as small as 1 cm, and thus, careful exploration should be considered during surgery. Most of the ovarian teratomas in patients with anti-N-methyl-D-aspartate receptor encephalitis are mature. Early operative treatment is safe and effective because it is associated with reduced risk of relapse and complete recovery.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Neoplasias Ovarianas/terapia , Teratoma/terapia , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Antineoplásicos Imunológicos/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Laparoscopia , Neoplasias Ovarianas/diagnóstico , Plasmaferese , Estudos Prospectivos , Recidiva , Rituximab/uso terapêutico , Teratoma/diagnóstico , Adulto JovemRESUMO
The development of photochromic fluorescence sensors with dynamic and multiple-signaling is beneficial to the improvement of biosensing/imaging precision. However, elaborate designs with complicated molecular structures are always required to integrate these functions into one molecule. By taking advantages of both redox-active/high loading features of two-dimensional (2D) manganese dioxide (MnO2) and dynamic fluorescence photoswitching of photochromic sensors, we here design a hybrid photochromic MnO2 glycosheet (Glyco-DTE@MnO 2 ) to achieve the photoswitchable imaging of intracellular glutathione (GSH). The photochromic glycosheet manifests significantly turn-on fluorescence and dynamic ON/OFF fluorescence signals in response to GSH, which makes it favorable for intracellular GSH double-check in targeted human hepatoma cell line (HepG2) through the recognition between ß-D-galactoside and asialoglycoprotein receptor (ASGPr) on cell membranes. The dynamic fluorescence signals and excellent selectivity for detection and imaging of GSH ensure the precise determination of cell states, promoting its potential applications in future disease diagnosis and therapy.
RESUMO
Despite the rapid development of imaging techniques, precise probe localization and modulation in living cells is still a challenging task. Here we show that the simple hybridization between a photochromic fluorescent glycoprobe and human serum albumin (HSA) enables a unique fluorescence "double-check" mechanism for precisely localizing and manipulating probe molecules in living cells. Docking of a carbohydrate-modified naphthalimide (Naph)-spiropyran (SP) dyad to a hydrophobic pocket of HSA produces the glycoprobe-protein hybrid, causing the protein conformation to fold as determined by small-angle X-ray scattering. We show that the Naph and merocyanine (the photoisomer of SP) fluorescence of the resulting hybrid can be reversibly switched by light in buffer solution and in target cells overexpressing the carbohydrate receptor.
Assuntos
Receptor de Asialoglicoproteína/análise , Benzopiranos/química , Corantes Fluorescentes/química , Indóis/química , Nitrocompostos/química , Albumina Sérica Humana/química , Sítios de Ligação , Fluorescência , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Luz , Simulação de Acoplamento Molecular , Naftalimidas/química , Imagem Óptica/métodos , Conformação ProteicaRESUMO
Multi-triggered DNA/bipyridinium dithienylethene (DTE) hybrid carboxymethyl cellulose (CMC)-based hydrogels are introduced. DTE exhibits cyclic and reversible photoisomerization properties, switching between the closed state (DTEc), the electron acceptor, and the open isomer (DTEo) that lacks electron acceptor properties. One system introduces a dual stimuli-responsive hydrogel containing CMC chains modified with electron donor dopamine sites and self-complementary nucleic acids. In the presence of DTEc and the CMC scaffold, a stiff hydrogel is formed, cooperatively stabilized by dopamine/DTEc donor-acceptor interactions and by duplex nucleic acids. The cyclic and reversible formation and dissociation of the supramolecular donor-acceptor interactions, through light-induced photoisomerization of DTE, or via oxidation and subsequent reduction of the dopamine sites, leads to hydrogels of switchable stiffness. Another system introduces a stimuli-responsive hydrogel triggered by one of three alternative signals. The stiff, multi-triggered hydrogel consists of CMC chains cross-linked by dopamine/DTEc donor-acceptor interactions, and by supramolecular K+-stabilized G-quadruplexes. The G-quadruplexes are reversibly separated in the presence of 18-crown-6 ether and reformed upon the addition of K+. The stiff hydrogel undergoes reversible transitions between high-stiffness and low-stiffness states triggered by light, redox agents, or K+/crown ether. The hybrid donor-acceptor/G-quadruplex cross-linked hydrogel shows shape-memory and self-healing features. By using three different triggers and two alternative memory-codes, e.g., the dopamine/DTEc or the K+-stabilized G-quadruplexes, the guided shape-memory function of the hydrogel matrices is demonstrated.
Assuntos
DNA Complementar/química , Hidrogéis/química , Compostos de Piridínio/química , Carboximetilcelulose Sódica/síntese química , Carboximetilcelulose Sódica/química , Éteres de Coroa/química , DNA Complementar/síntese química , DNA Complementar/genética , Dopamina/síntese química , Dopamina/química , Quadruplex G , Hidrogéis/síntese química , Isomerismo , Hibridização de Ácido Nucleico , Oxirredução , Fenômenos Físicos , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Raios UltravioletaRESUMO
Identification of the configuration for the photoresponsive oligonucleotide plays an important role in the ingenious design of DNA nanomolecules and nanodevices. Due to the limited resolution and sensitivity of present methods, it remains a challenge to determine the accurate configuration of photoresponsive oligonucleotides, much less a precise description of their photoconversion process. Here, we used an aerolysin (AeL) nanopore-based confined space for real-time determination and quantification of the absolute cis/ trans configuration of each azobenzene-modified oligonucleotide (Azo-ODN) with a single molecule resolution. The two completely separated current distributions with narrow peak widths at half height (<0.62 pA) are assigned to cis/ trans-Azo-ODN isomers, respectively. Due to the high current sensitivity, each isomer of Azo-ODN could be undoubtedly identified, which gives the accurate photostationary conversion values of 82.7% for trans-to- cis under UV irradiation and 82.5% for cis-to- trans under vis irradiation. Further real-time kinetic evaluation reveals that the photoresponsive rate constants of Azo-ODN from trans-to- cis and cis-to -trans are 0.43 and 0.20 min-1, respectively. This study will promote the sophisticated design of photoresponsive ODN to achieve an efficient and applicable photocontrollable process.
Assuntos
Toxinas Bacterianas/química , Nanoporos , Oligonucleotídeos/análise , Proteínas Citotóxicas Formadoras de Poros/química , Processos Fotoquímicos , Estereoisomerismo , Fatores de TempoRESUMO
BACKGROUND: Because of the rarity of endometrioid borderline ovarian tumours (EBOTs), there is a paucity of data concerning the natural history and prognosis of this condition. Thus, the objective of our study was to establish the feasibility of fertility preservation in young women with EBOTs, as well as their oncological and reproductive outcomes. METHODS: Consecutive patients with EBOTs, treated at a tertiary referral centre during a span of 22 years, were retrospectively analysed. Recurrence-free interval, as well as its association with the type of surgery and with other clinical and pathological features, was assessed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: Of the 59 patients studied, the median follow-up time was 30 months (range, 6-177 months). Nine (15.3%) patients developed 13 recurrences 6-137 months after the initial surgeries, including three patients (5.1%; n = 3/59) who developed six invasive recurrences 8, 18 and 68 months after their initial surgeries. Conservative surgery showed a tendency towards a high recurrence rate (17.2% versus 13.3%); however, this difference was not significant (p = 0.45). The 5-year recurrence-free survival rate was significantly higher in the oophorectomy group than in the cystectomy group (p = 0.001). Cox regression analysis showed that none of the variables assessed were associated with an increased hazard ratio for recurrence, except for a younger age at diagnosis (p = 0.021). Of 20 patients who attempted to conceive, three pregnancies among two patients (10.0%) resulted in two live births. CONCLUSIONS: Conservative surgery with unilateral adnexectomy can be proposed for young women with EBOTs with fertility desire; however, the reproductive result is not satisfactory. In addition, careful evaluations of the endometria should be offered during the initial surgery and follow-up period. TRIAL REGISTRATION: Retrospectively registered.
Assuntos
Tratamento Conservador , Preservação da Fertilidade , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Terapia Combinada , Tratamento Conservador/efeitos adversos , Tratamento Conservador/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto JovemRESUMO
The light-induced reversible and cyclic reconfiguration of constitutional dynamic networks, consisting of supramolecular nucleic acid structures as constituents and a photoisomerizable trans/cis-azobenzene-functionalized nucleic acid as the trigger is demonstrated. In addition, the cyclic photochemical reconfiguration of the constitutional dynamic networks guides the switchable on/off operation of an emerging hemin/G-quadruplex DNAzyme.
Assuntos
DNA/química , Luz , Compostos Azo/química , Catálise , DNA Catalítico/química , DNA Catalítico/metabolismo , Quadruplex G , Hemina/química , Isomerismo , Oxazinas/química , OxirreduçãoRESUMO
OBJECTIVE: To identify the prevalence of unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma and compare clinical consequences after hysterectomy with and without transvaginal scalpel morcellation (TVSM). METHODS: In this retrospective study, the medical records of patients who had unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma between 2009 and 2013 were reviewed. RESULTS: Among 3021 patients who underwent total hysterectomy for presumed leiomyoma, 18 (1/168, 0.60%) had unexpected uterine sarcoma (5 [1/604, 0.17%] had leiomyosarcoma and 13 [1/232, 0.43%] had low-grade endometrial stromal sarcoma). The risk of unexpected leiomyosarcoma increased steadily in ages from the 40s to the 50s, whereas the risk of unexpected endometrial stromal sarcoma (ESS) decreased steadily in the same period. The unexpected sarcoma was identified in 7 (1/158, 0.63%) of 1104 patients treated by laparoscopy and 11 (1/174, 0.57%) of 1917 patients by laparotomy. Transvaginal scalpel morcellation was performed to extract the uterus in majority (78.53%) of the patients with total laparoscopic hysterectomy. Sixteen (88.89%) cases were low grade, and 2 (11.11%) were high grade: 17 at stage I and 1 at stage II. Nine patients underwent a secondary operation, and 11 patients received adjuvant therapy postoperatively. Except for 1 patient with additional power morcellation, all patients with unexpected ESS survived without recurrence after total hysterectomy with and without TVSM, with mean follow-ups of 25.20 (16-36) months and 32.57 (21-50) months, respectively. CONCLUSIONS: The overall incidence of unexpected uterine sarcoma after total hysterectomy for presumed leiomyoma was low. Low-grade endometrial stromal sarcoma was the dominant subtype of unexpected uterine sarcoma in the present study. Currently, incidental TVSM of unexpected ESS during total laparoscopic hysterectomy seemed to cause no additional increase in sarcoma dissemination in the short-term.