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Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.
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Nucléolo Celular , Corantes Fluorescentes , Mitocôndrias , Mitocôndrias/metabolismo , Mitocôndrias/química , Humanos , Corantes Fluorescentes/química , Nucléolo Celular/metabolismo , Células HeLa , Simulação de Acoplamento Molecular , Imagem Óptica , Potencial da Membrana MitocondrialRESUMO
Normally, small-molecule fluorescent probes dependent on the mitochondrial membrane potential (MMP) are invalid for fixed cells and tissues, which limits their clinical applications when the fixation of pathological specimens is imperative. Given that mitochondrial morphology is closely associated with disease, we developed a long-chain mitochondrial probe for fixed cells and tissues, DMPQ-12, by installing a C12-alkyl chain into the quinoline moiety. In fixed cells stained with DMPQ-12, filament mitochondria and folded cristae were observed with confocal and structural illumination microscopy, respectively. In titration test with three major phospholipids, DMPQ-12 exhibited a stronger binding force to mitochondria-exclusive cardiolipin, revealing its targeting mechanism. Moreover, mitochondrial morphological changes in the three lesion models were clearly visualized in fixed cells. Finally, by DMPQ-12, three kinds of mitochondria with different morphologies were observed in situ in fixed muscle tissues. This work breaks the conventional concept that organic fluorescent probes only stain mitochondria with normal membrane potentials and opens new avenues for comprehensive mitochondrial investigations in research and clinical settings.
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Mitochondrial DNA (mtDNA) is pivotal for mitochondrial morphology and function. Upon mtDNA damage, mitochondria undergo quality control mechanisms, including fusion, fission, and mitophagy. Real-time monitoring of mtDNA enables a deeper understanding of its effect on mitochondrial function and morphology. Controllable induction and real-time tracking of mtDNA dynamics and behavior are of paramount significance for studying mitochondrial function and morphology, facilitating a deeper understanding of mitochondria-related diseases. In this work, a fluorescent platinum complex was designed and developed that not only induces mitochondrial DNA (mtDNA) aggregation but also triggers mitochondrial autophagy (mitophagy) through the MDV pathway for damaged mtDNA clearance in living cells. Additionally, this complex allows for the real-time monitoring of these processes. This complex may serve as a valuable tool for studying mitochondrial microautophagy and holds promise for broader applications in cellular imaging and disease research.
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DNA Mitocondrial , Corantes Fluorescentes , Mitofagia , DNA Mitocondrial/metabolismo , Humanos , Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Platina/química , Células HeLaRESUMO
BACKGROUND: Chronic diarrhea is difficult to prevent and treat due to its complex etiology and pathogenesis. It places a huge burden on patients and public healthcare. It is known that the regulation of body homeostasis relies heavily on calcium. However, in the general population, the relationship between calcium and chronic diarrhea remains uncertain. METHODS: We assessed the association between serum calcium and diarrhea using data from the 2005-2010 National Health and Nutrition Examination Survey (NHANES). Serum calcium level was measured from collected blood samples. Diarrhea was assessed using the Bristol Stool Scale (BSFS) (types 1-7). The stability of the results was assessed using logistic regression and sensitivity analysis. The dose-response association between serum calcium and the risk of diarrhea was analyzed using a restricted cubic spline plot. RESULTS: This study included 12,342 participants. In each of the five models, an increased calcium level was negatively associated with the incidence of diarrhea (OR[95%CI]:0.26 [0.13-0.53], 0.28 [0.14-0.58], 0.4 [0.19-0.82], 0.27 [0.11-0.64] and 0.24 [0.10-0.59], respectively). When serum calcium was analyzed as a categorical variable, a significant association between serum calcium and diarrhea prevalence was found. The restricted cubic spline plot showed a linear relationship between serum calcium and diarrhea. Sensitivity analysis confirmed that the results were stable. CONCLUSION: The results of our cross-sectional study suggest that a higher level of serum calcium may reduce the incidence of diarrhea. In the future, this finding should be further validated in a randomized controlled trial.
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Cálcio , Diarreia , Humanos , Inquéritos Nutricionais , Estudos Transversais , Incidência , Diarreia/epidemiologiaRESUMO
PURPOSE: To evaluate the influence of K-line on the outcome of open-door laminoplasty versus anterior cervical corpectomy decompression and fusion (ACCF) for patients with more than two levels of ossification of the posterior longitudinal ligament (OPLL). METHODS: 60 patients undergoing open-door laminoplasty and 62 patients undergoing ACCF from January 2013 to January 2020 with more than 2 years of follow-up were included. Eighty-four cases with the ossification mass not beyond the K-line were grouped as K-line (+), while thirty-eight cases were grouped as K-line (-). The operation time, intraoperative blood loss, hospital stay, preoperative, postoperative, and last follow-up JOA scores, and postoperative complications were investigated. RESULTS: The improvement rate of JOA scores after posterior approaches in cases of group K-line (+) and K-line (-) was 72.4% and 53.1%, respectively, which showed a significant difference (P < 0.01). In group K-line (+), the improvement of JOA scores for open-door laminoplasty was 73.4% and 71.8% for ACCF, which showed no significant difference (P > 0.05). In group K-line (-), the improvement of JOA scores for ACCF was 52.1% and 42.9% for open-door laminoplasty, which showed a significant difference (P < 0.05). The incidence of C5 palsy was significantly lower in cases with ACCF than in cases with open-door laminoplasty (P < 0.05). CONCLUSION: For patients with more than two levels of OPLL, preoperative K-line (+) predicates a better outcome than K-line (-). For cases with K-line (-), ACCF provides better neurologic function recovery. For patients with K-line (+), open-door laminoplasty provides the same neurologic function recovery of ACCF.
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Laminoplastia , Ossificação do Ligamento Longitudinal Posterior , Fusão Vertebral , Humanos , Ligamentos Longitudinais/cirurgia , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Ossificação do Ligamento Longitudinal Posterior/complicações , Resultado do Tratamento , Osteogênese , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures. METHOD: A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed. RESULTS: This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2-5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8-18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5-7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1-0.6). CONCLUSIONS: This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs.
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Fraturas do Úmero , Fraturas do Ombro , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Úmero , Placas Ósseas , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Fraturas do Úmero/cirurgiaRESUMO
Inflammation exists in the microenvironment of most, if not virtually all, tumors, which greatly exacerbates the difficulty of cancer treatment. Considering the superiority of activatable photosensitizers (PSs), a novel strategy of 'making friends with the enemy' for tumor treatment was proposed. In this strategy, the "enemy" refers to inflammatory cytokines and the tumor site is targeted by detecting the enemy. Upon detection, a dichromatic fluorescence signal is released and the PS is activated specifically by the inflammatory cytokines. In this study, a multifunctional PS (TPE-PTZ-Py) was rationally designed, which can be activated specifically under the synergistic action of hypochlorous acid (HClO) (one kind of inflammatory cytokines) and acid (one typical marker of tumor), and output a ratiometric fluorescence signal simultaneously. The sulfoxide analogue (TPE-PTZO-PyH) as the response product effectively produced 1O2 (1.8-fold higher than that obtained with Rose Bengal) and showed high phototoxicity (IC50 < 7.6 µM). More importantly, imaging analyses confirmed that TPE-PTZ-Py could be activated in human cervical cancer tissue. To date, several phenothiazine (PTZ)-based fluorescent probes have been developed for the selective sensing and imaging of HClO in subcellular organelles; however, this is the first phenothiazine-based nanodrug designed for the treatment of inflammation-associated tumors with a few side effects.
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Fotoquimioterapia , Neoplasias do Colo do Útero , Feminino , Corantes Fluorescentes , Humanos , Ácido Hipocloroso/análise , Microscopia de Fluorescência/métodos , Microambiente Tumoral , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
Hydrazine is widely used in industrial and agricultural production, but excessive hydrazine possesses a serious threat to human health and environment. Here two new ratiometric fluorescence probes, DDP and DDC, with the hydroxyl coumarin chalcone unit as the sensing site are developed, which can achieve colorimetric and ratiometric recognition for hydrazine with good sensitivity, excellent selectivity, and anti-interference. The calculated fluorescence limits of detections are 0.26 µM (DDC) and 0.14 µM (DDP). The ratiometric fluorescence response to hydrazine is realized through the adjustment of donor and receptor units in coumarin conjugate structure terminals, accompanied by fluorescence peak shift about 200 nm (DDC, 188 nm; DDP, 229 nm). Stronger electropositivity in the carbon-carbon double bond is helpful to the first phase addition reaction between the probe and hydrazine. Higher phenol activity in the hydroxyl coumarin moiety will facilitate the following dihydro-pyrazole cyclization reaction. In addition, both of these probes realized the convenient detection of hydrazine vapor. The probes were also successfully applied to detect hydrazine in actual water samples, different soils, and living cells.
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Chalcona , Chalconas , Carbono , Cumarínicos/química , Corantes Fluorescentes/química , Humanos , Hidrazinas/química , Radical Hidroxila , Fenóis , Pirazóis , Solo , Espectrometria de Fluorescência , ÁguaRESUMO
The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti-tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
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Neoplasias , Fotoquimioterapia , Pontos de Checagem do Ciclo Celular , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
The misregulation of nucleic acids behavior leads to cell dysfunction and induces serious diseases. A ratiometric fluorescence probe is a powerful tool to study the dynamic behavior and function relationships of nucleic acids. However, currently, no such effective probe has been reported for in situ, real-time tracking of nucleic acids in living cells and tissue sections. Herein, the unique probe named QPP-AS was rationally designed for ratiometric fluorescence response to nucleic acids through skillful regulation of the intramolecular charge-transfer capabilities of the electron acceptor and donor. Encouraged by the advantages of the selective nucleic acid response, ideal biocompatibility, and high signal-to-noise ratio, QPP-AS has been applied for in situ, real-time ratiometric fluorescence imaging of nucleic acids in living cells for the first time. Furthermore, we have demonstrated that QPP-AS is capable of visualizing the dynamic behavior of nucleic acids during different cellular processes (e.g., cell division and apoptosis) by ratiometric fluorescence imaging. More significantly, QPP-AS has been successfully used for ratiometric fluorescence imaging of nucleic acids in human tissue sections, which provides not only the cell contour, nuclear morphology, and nuclear-plasma ratio but also the nucleic acid content information and may greatly improve accuracy in clinicopathological diagnosis.
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Adenocarcinoma Bronquioloalveolar/diagnóstico por imagem , Corantes Fluorescentes/química , Ácidos Nucleicos/análise , Imagem Óptica , Células A549 , HumanosRESUMO
Developing novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 µm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.
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Irídio/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Morte Celular , Linhagem Celular Tumoral , Diagnóstico por Imagem , Feminino , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
PURPOSE: Adolescent idiopathic scoliosis (AIS) is a common type of idiopathic scoliosis. Previous studies reported that the incidence of intraspinal abnormalities among the presumed idiopathic scoliosis was 13-43%. Intraspinal abnormalities were also considered increasing the risks of progressing of scoliosis and neurological complications following scoliosis corrective surgery. The surgical strategy of presumed adolescent idiopathic scoliosis (PAIS) associated with intraspinal abnormalities remains controversial. The purpose of this study was to investigate whether one-stage posterior surgery safe and effective for the PAIS patients associated with intraspinal abnormalities. MATERIALS AND METHODS: One hundred and thirteen consecutive patients who underwent one-stage posterior correction surgery were included. Thirty PAIS patients with intraspinal abnormalities without preoperative neurological symptoms were matched with eighty-three AIS patients for sex, age, blood loss, operating time, number of levels and location of instrumentation and curve magnitude. Radiographic and clinical parameters of the patients were evaluated before surgery, within 1 week after surgery, and more than 3 years at the last follow-up for complications and changes in main curve correction, global coronal balance, thoracic kyphosis, sagittal vertical axis, and ODI scores. RESULTS: On average, the duration of follow-up was 51.5 months in the PAIS group compared to 52.5 months in the AIS group. The preoperative mean major coronal curve was 79.6° (ranged 56.2°-106.7°) and improved to 22.4° (ranged 6.4°-58.1°) at the last follow-up for a 71.9% of correction in the AIS group. The preoperative mean major coronal curve was 80.4° (ranged 63.4°-108.1°) and improved to 23.2° (ranged 4.8°-66.2°) at the last follow-up for a 71.1% of correction in PAIS group. The preoperative ODI score was 32.4 (10-42) in the PAIS group and improved to 11.4 (4-22) at last follow-up, 33.4 (12-42) in the AIS group and improved to 11.5 (5-22) at last follow-up. The global coronal balance, TK and SVA were all significantly improved after surgery and maintained to the last follow-up in the two groups. The neurological complications were observed in 3.3% of PAIS patients and 3.6% of AIS patients. No statistical difference in the parameters between the two groups was observed at the last follow-up. CONCLUSION: One-stage posterior corrective surgery is safe and effective in PAIS patients associated with intraspinal abnormalities without preoperative neurological symptoms. Surgical guidelines of AIS are appropriate for the treatment of PAIS patients associated with intraspinal abnormalities.
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Cifose , Escoliose , Fusão Vertebral , Adolescente , Seguimentos , Humanos , Estudos Retrospectivos , Vértebras Torácicas , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to compare the pedicle screw placement accuracy and surgical outcomes between 3D-printed (3DP) drill guide template technique and freehand technique in spinal deformity surgery. METHODS: A comprehensive systematic literature search of databases (PubMed, Embase, Cochrane Library, and Web of Science) was conducted. The meta-analysis compared the pedicle screw placement accuracy and other important surgical outcomes between the two techniques. RESULTS: A total of seven studies were included in the meta-analysis, comprising 87 patients with 1384 pedicle screws placed by 3DP drill guide templates and 88 patients with 1392 pedicle screws placed by freehand technique. The meta-analysis results revealed that the 3DP template technique was significantly more accurate than the freehand technique to place pedicle screws and had a higher rate of excellently placed screws (OR 2.22, P < 0.001) and qualifiedly placed screws (OR 3.66, P < 0.001), and a lower rate of poorly placed screws (OR 0.23, P < 0.001). The mean placement time per screw (WMD-1.99, P < 0.05), total screw placement time (WMD-27.86, P < 0.001), and blood loss (WMD-104.58, P < 0.05) were significantly reduced in the 3DP template group compared with the freehand group. Moreover, there was no significant statistical difference between the two techniques in terms of the operation time and correction rate of main bend curve. CONCLUSIONS: This study demonstrated that the 3DP drill guide template was a promising tool for assisting the pedicle screw placement in spinal deformity surgery and deserved further promotion.
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Parafusos Pediculares , Fusão Vertebral , Cirurgia Assistida por Computador , Humanos , Procedimentos Neurocirúrgicos , Impressão TridimensionalRESUMO
BACKGROUND: Obtaining and maintaining final shoulder balance after the entire treatment course is essential for early-onset scoliosis (EOS) patients. The relatively small number of growing-rod (GR) graduates who complete final fusion has resulted in an overall paucity of research on the GR treatment of EOS and a lack of research on the shoulder balance of EOS patients during GR treatment. METHODS: Twenty-four consecutive patients who underwent GR treatment until final fusion were included. Radiographic shoulder balance parameters, including the radiographic shoulder height (RSH), clavicle angle (CA), and T1 tilt angle (T1T), before and after each step of the entire treatment were measured. Shoulder balance changes from GR implantation to the last follow-up after final fusion were depicted and analysed. Demographic data, surgical-related factors, and radiographic parameters were analysed to identify risk factors for final shoulder imbalance. The shoulder balance of patients at different time points was further analysed to explore the potential effect of the series of GR treatment steps on shoulder balance. RESULTS: The RSH showed substantial improvement after GR implantation (P = 0.036), during the follow-up period after final fusion (P = 0.021) and throughout the entire treatment (P = 0.011). The trend of change in the CA was similar to that of the RSH, and the T1T improved immediately after GR implantation (P = 0.037). Further analysis indicated that patients with shoulder imbalance before final fusion showed significantly improved shoulder balance after fusion (P = 0.045), and their RSH values at early postfusion and the final follow-up did not show statistically significant differences from those in the prefusion shoulder balance group (P > 0.05). Early postfusion shoulder imbalance (odds ratio (OR): 19.500; 95% confidence interval (CI) = 1.777-213.949; P = 0.015) was identified as an independent risk factor for final shoulder imbalance. CONCLUSIONS: Shoulder balance could be improved by GR implantation but often changes during the multistep lengthening process, and the final result is relatively unpredictable. Final fusion could further adjust the prefusion shoulder imbalance. Focusing on the prefusion shoulder balance of GR graduates and providing patients with early shoulder balance after fusion might be necessary.
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Escoliose , Fusão Vertebral , Seguimentos , Humanos , Equilíbrio Postural , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Ombro/diagnóstico por imagem , Ombro/cirurgia , Fusão Vertebral/efeitos adversos , Vértebras Torácicas , Resultado do TratamentoRESUMO
Ferroptosis regulates cell death through reactive oxygen species (ROS)-associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual-targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis-related diseases.
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Núcleo Celular/metabolismo , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Ferroptose , Corantes Fluorescentes/síntese química , Humanos , Gotículas Lipídicas/química , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismoRESUMO
The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand L1 Pt(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-L1 Pt(dien) complex was determined by NMR. The structure reveals that L1 Pt(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via π-π stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures.
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BACKGROUND: Irritable bowel syndrome (IBS) has been gradually recognized as a disorder of the brain-gut interaction, but the molecular changes in the brain and colon that occur in disease development remain poorly understood. We employed proteomic analysis to identify differentially expressed proteins in both the brain and colon of three IBS models. METHODS: To explore the relevant protein abundance changes in the brain and colon, isobaric tags for relative and absolute quantitation (iTRAQ), liquid chromatography and tandem mass spectrometry (LC-MS) and Western blotting methods were used in three IBS models, including maternal separation (MS, group B), chronic wrap restraint stress (CWRS, group C) and a combination of MS and CWRS (group D). RESULTS: We identified 153, 280, and 239 proteins that were common and differentially expressed in the two tissue types of groups B, C and D, respectively; 43 differentially expressed proteins showed the same expression changes among the three groups, including 25 proteins upregulated in the colon and downregulated in the brain, 7 proteins downregulated in the colon and upregulated in the brain, and 3 proteins upregulated and 8 downregulated in both tissues. Gene ontology analysis showed that the differentially expressed proteins were mainly associated with cellular assembly and organization and cellular function and maintenance. Protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the differentiated proteins were mainly involved in the protein ubiquitination pathway and mitochondrial dysfunction. CONCLUSIONS: Taken together, the data presented represent a comprehensive and quantitative proteomic analysis of the brain and colon in IBS models, providing new evidence of an abnormal brain-gut interaction in IBS. These data may be useful for further investigation of potential targets in the diagnosis and treatment of IBS.
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PURPOSE: In addition to changes in the skeletal system after spinal osteotomy for treatment of kyphotic deformity in advanced-stage AS patients, many other systemic changes associated with the patients' quality of life were reported. The purpose of this study was to conduct a systemic review of the literature to determine systemic changes associated with patients' quality of life following correction of kyphotic deformity secondary to ankylosing spondylitis. METHODS: We searched the databases PubMed, EMBASE, Clinicalkey and Cochrane Library without time restriction. Selected papers were assessed by published guidelines. We investigated systemic changes associated with patients' quality of life after surgical treatment of advanced ankylosing spondylitis. RESULTS: The initial search yielded 888 citations. Twelve of these studies met the inclusion and exclusion criteria. Two were level II evidence study, and ten were level III evidence studies. Changes were reported including aorta length, abdominal morphology, digestive function, cardiopulmonary function, psychological status, and sexual activity. CONCLUSIONS: In addition to skeletal changes after spinal osteotomy for treatment of kyphotic deformity in advanced-stage AS patients, many other changes were reported. Spine surgeons should pay more attention to these life quality-related changes and be aware of potential risks when performing surgery for advanced-stage AS patients. These slides can be retrieved under Electronic Supplementary Material.
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Cifose , Espondilite Anquilosante , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Osteotomia , Qualidade de Vida , Coluna Vertebral , Espondilite Anquilosante/complicações , Espondilite Anquilosante/cirurgia , Resultado do TratamentoRESUMO
G-quadruplex DNA show structural polymorphism, leading to challenges in the use of selective recognition probes for the accurate detection of G-quadruplexes inâ vivo. Herein, we present a tripodal cationic fluorescent probe, NBTE, which showed distinguishable fluorescence lifetime responses between G-quadruplexes and other DNA topologies, and fluorescence quantum yield (Φf ) enhancement upon G-quadruplex binding. We determined two NBTE-G-quadruplex complex structures with high Φf values by NMR spectroscopy. The structures indicated NBTE interacted with G-quadruplexes using three arms through π-π stacking, differing from that with duplex DNA using two arms, which rationalized the higher Φf values and lifetime response of NBTE upon G-quadruplex binding. Based on photon counts of FLIM, we detected the percentage of G-quadruplex DNA in live cells with NBTE and found G-quadruplex DNA content in cancer cells is 4-fold that in normal cells, suggesting the potential applications of this probe in cancer cell detection.
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DNA/química , Quadruplex G , Linhagem Celular Tumoral , DNA/análise , Humanos , FótonsRESUMO
It is of great significance to track the platinum drugs in real time with super-resolution to elucidate their mechanism of action, such as their behavior and distribution in live cells. Such information is required for further drug development. However, it is always challenging to design platinum complexes suitable for such research. Herein, we design a luminescent building block (L) for metal complexes and a dinuclear platinum complex (Pt2 L) for super-resolution imaging. Because of its super-large Stokes shift and excellent photophysical properties, Pt2 L is capable of serving as an ideal candidate for super-resolution imaging with extremely low luminescence background and high photobleaching resistance. Moreover, upon light stimulation, a matter flux of Pt2 L escaping from autolysosomes to nucleus was observed, which represents a new transportation path. Utilizing the photoactivated escape properties, we can regulate the nuclear accessibility of Pt2 L form autolysosomes with photo-selectivity, which provides a new way to improve the targeting of platinum drugs.