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1.
Int J Nanomedicine ; 16: 6129-6140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511910

RESUMO

Purpose: With the development of nanomedicine, microwave ablation enhanced by multifunctional nanoplatforms has been widely studied for synergistic cancer therapy. Though scientists have got a lot of significant achievements in this field, the detailed molecular mechanisms and potential targets of microwave ablation enhanced by multifunctional nanoplatforms still need further exploration. In this study, we found that a kind of magnetite Fe3O4 nanoparticles (Fe3O4 NPs) could induce severe endoplasmic reticulum stress and activate cancer apoptosis under the irradiation of mild microwave. Methods: In this study, plenty of studies including cell immunofluorescence, mitochondrial membrane potential, electron microscopy, atomic force microscopy and microwave ablation in vivo were conducted to explore the molecular mechanisms and potential targets of microwave ablation enhanced by the Fe3O4 NPs. Results: The IRE1-ASK1-JNK pathway was strongly activated in A375 cells treated with both Fe3O4 NPs and mild microwave. The endoplasmic reticulum of the A375 cells was significantly dilated and exhibited ballooning degeneration. By investigating the mitochondrial membrane potential (ΔΨm), we found that the mitochondria of cancer cells had been significantly damaged under microwave treatment coupled with Fe3O4 NPs. In addition, melanoma of B16F10-bearing mice had also been effectively inhibited after being treated with Fe3O4 NPs and microwave. Conclusion: In this study, we found that a kind of magnetite Fe3O4 nanoparticles could induce severe ER stress and activate cancer apoptosis under mild microwave irradiation. Apparent apoptosis had been observed in the A375 cells under a scanning electron microscope and transmission electron microscope. Moreover, melanoma had also been inhibited effectively in vivo. As a result, the endoplasmic reticulum stress is a promising target with clinical potential in nanomedicine and cancer therapy.

2.
J Environ Manage ; 297: 113414, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34351303

RESUMO

Great deal pathogenic bacteria and malodorous gases are hidden in municipal solid waste (MSW), which poses excellent environmental sanitation risks for sanitation workers and residents, and preventive measures should be implemented. In this study, the simultaneous annihilation of microorganisms and volatile organic compounds (VOCs) with slightly acidic electrolyzed water (SAEW) was investigated in an MSW storage room of a residential community in Shanghai, China. The microbial population of airborne, surfaces and handles of waste bins, hands of sanitation workers and the main components of VOCs were measured. The results indicated that the bacterial reduction efficiencies of SAEW with an available chlorine concentration (ACC) of 50-100 mg/L on surfaces and handles of waste bins and sanitation workers' hands were 22.7%-84.1%. Also, SAEW effectively reduced the average population of airborne bacteria and fungi by 358 and 378 colony-forming units (CFU)/m3 and decreased the detection rates of coliforms by 14.2%-51.9%. The concentrations of most VOCs were reduced by 21.4%-88.3% after spraying SAEW. And the accumulated values of carcinogenic and noncarcinogenic risks also tended to decrease with spraying SAEW. These findings imply that SAEW has significant application potential to control environmental sanitation risks in MSW storage rooms.


Assuntos
Desinfetantes , Compostos Orgânicos Voláteis , China , Desinfecção , Humanos , Resíduos Sólidos , Água
3.
Thorac Cancer ; 12(4): 468-474, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33398925

RESUMO

BACKGROUND: Identification of small pulmonary nodules is challenging in a limited intrathoracic field during minimally invasive video-assisted thoracoscopic surgery (VATS), and preoperative localization is required. Various techniques have been reported with some failure and complications. Here, we compare the feasibility and safety between electromagnetic navigation bronchoscopic marking and computed tomography (CT)-guided percutaneous marking using indocyanine green (ICG) and iopamidol. METHODS: A total of 47 patients with small-sized pulmonary nodules, scheduled to undergo video-assisted thoracoscopic limited resection, were enrolled in this study. A mixture of diluted ICG and iopamidol was injected into the lung parenchyma as a marker, using CT-guided percutaneous or electromagnetic navigation bronchoscopic injection techniques and the results were examined and compared. RESULTS: A total of 35 and 12 patients underwent preoperative marking by percutaneous injection and electromagnetic navigation bronchoscopic injection, respectively, in which a marker was detected in 33/35 (94.3%) and 12/12 (100%) patients. No combination of these procedures was performed in any patient. All markers were successfully detected in three patients who underwent injection marking at two different lesion sites. Pneumothorax occurred in five patients (14%) in the percutaneous marking group, which was relieved in all patients without the necessity for chest tube drainage. No other complication was observed in this study. CONCLUSIONS: Electromagnetic navigation bronchoscopic injection techniques using indocyanine green fluorescence plus iopamidol are safe and effective, and comparable with CT-guided localization. Furthermore, a bronchoscopic approach enables marking of multiple lesion areas without increasing patient risk, especially for puncture-related pneumothorax. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Either computed tomography (CT)-guided percutaneous or electromagnetic navigation bronchoscopic injection techniques can be used for preoperative marking of pulmonary nodules with indocyanine green (ICG) fluorescence. WHAT THIS STUDY ADDS: Indocyanine green (ICG) is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery (VATS). A bronchoscopic injection approach enables marking of multiple lesion areas without increasing the risk of pneumothorax.

4.
Sci Adv ; 6(48)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33239287

RESUMO

Metabolic traits of macrophages can be rewired by insulin-like growth factor 2 (IGF2); however, how IGF2 modulates macrophage cellular dynamics and functionality remains unclear. We demonstrate that IGF2 exhibits dual and opposing roles in controlling inflammatory phenotypes in macrophages by regulating glucose metabolism, relying on the dominant activation of the IGF2 receptor (IGF2R) by low-dose IGF2 (L-IGF2) and IGF1R by high-dose IGF2. IGF2R activation leads to proton rechanneling to the mitochondrial intermembrane space and enables sustained oxidative phosphorylation. Mechanistically, L-IGF2 induces nucleus translocation of IGF2R that promotes Dnmt3a-mediated DNA methylation by activating GSK3α/ß and subsequently impairs expression of vacuolar-type H+-ATPase (v-ATPase). This sequestrated assembly of v-ATPase inhibits the channeling of protons to lysosomes and leads to their rechanneling to mitochondria. An IGF2R-specific IGF2 mutant induces only the anti-inflammatory response and inhibits colitis progression. Together, our findings highlight a previously unidentified role of IGF2R activation in dictating anti-inflammatory macrophages.

5.
Am J Transl Res ; 12(7): 3613-3628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774722

RESUMO

Single nucleotide polymorphisms (SNPs) in the genes coding for leptin (LEP) and its receptor (LEPR) might regulate energy balance and be implicated in the development of colorectal cancer (CRC). In the present investigation, 1,003 CRC cases and 1,303 matched controls was compared. Five functional SNPs in LEP and LEPR genes were chosen to evaluate the correlation of these chosen SNPs with CRC susceptibility. We used the SNPscanTM genotyping assay to genotype LEP and LEPR SNPs. A significantly decreased risk of CRC was found to be associated with the LEPR rs6588147 polymorphism (GA vs. GG: crude P=0.007 and GA/AA vs. GG: crude P=0.018). With adjustments for risk factors (e.g. age, gender, drinking, BMI and smoking), these associations were not changed. In subgroup analyses, the association of LEP rs2167270 with a decreased risk of CRC was found in the ≥61 years old subgroup. For LEPR rs1137100, the association of this SNP with an increased susceptibility of CRC was found in the BMI <24 kg/m2 subgroup. In subgroup analyses for LEPR rs6588147, we identified that this locus also decreased the susceptibility of CRC in the male subgroup, <61 years old subgroup, never smoking subgroup and never drinking subgroup. For LEPR rs1137101, the relationship of this polymorphism with a decreased susceptibility to CRC was found in the never drinking subgroup. In summary, the present study highlights that LEPR rs6588147, rs1137101 and LEP rs2167270 may decrease the risk of CRC. However, LEPR rs1137100 is associated with susceptibility to CRC. Further case-control studies with larger sample sizes should be conducted to validate our findings.

6.
Front Neurosci ; 14: 776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848555

RESUMO

Recently, ferroptosis has been revealed as a new form of regulated cell death. Distinct from apoptosis and necrosis, ferroptosis is evoked by iron-dependent lipid peroxidation. Furthermore, the metabolism of iron, lipids, and amino acids plays a significant regulatory role in ferroptosis, which can be reversed by glutathione peroxidase 4 and ferroptosis suppressor protein 1. Ferroptosis is implicated in the onset and development of numerous neurological diseases. Emerging studies have reported that ferroptosis induces and aggravates brain tissue damage following cerebral ischemia, whereas inhibition of ferroptosis dramatically attenuates induced damage. In this review, we have summarized the mechanistic relationship between ferroptosis and cerebral ischemia, including through iron overload, downregulation of glutathione peroxidase 4, and upregulation of lipid peroxidation. Although considerable attention has been paid to the effect of ferroptosis on cerebral ischemic injury, specific mechanisms need to be experimentally confirmed, including how cerebral ischemia induces ferroptosis and how ferroptosis deteriorates cerebral ischemia.

7.
Technol Cancer Res Treat ; 19: 1533033820928072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489143

RESUMO

OBJECTIVE: The aim of the study is to determine the role of nuclear receptor coactivator 2 in cell proliferation and invasion ability of gastric cancer cells and to explore its possible mechanisms. METHODS: Immunohistochemical staining was used to determine NCOA2 gene expression in gastric cancer. Western blotting was used to detect Wnt signal pathways-related protein expression. Colony formation assays, Cell Counting Kit-8 assays, and transwell assays were used to determine cell proliferation, metastasis, and invasion ability of gastric cancer cells. A flow cytometric apoptosis tests determine gastric cancer cell apoptosis ability after inhibition of the expression of nuclear receptor coactivator 2. Subcutaneous mouse models were used to determine the gastric cancer growth and peritoneal metastasis differences after inhibition the expression of nuclear receptor coactivator 2. RESULTS: The expression of nuclear receptor coactivator 2 in gastric cancer cells is high (P < .01), including lymph node metastasis, TNM staging, and gender differences in nuclear receptor coactivator 2 expression were statistically significant (P < .01). Short interfering nuclear receptor coactivator 2 could inhibit the proliferation and invasion ability of gastric cancer cells. Short interfering nuclear receptor coactivator 2 promotes the apoptosis of gastric cancer cells. Animal experiments showed that short interfering nuclear receptor coactivator 2 could inhibit the growth and invasion of gastric cancer-transplantable tumors. Knockdown of the expression of nuclear receptor coactivator 2 inhibited the Wnt/ß-catenin signaling pathway in the gastric cancer cells. CONCLUSIONS: Knockdown of the expression of nuclear receptor coactivator 2 can inhibit the proliferation and invasion of human gastric cancer in vitro and in vivo. The underlying mechanism of NOCA2 affects the Wnt signaling pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Coativador 2 de Receptor Nuclear/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Idoso , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Coativador 2 de Receptor Nuclear/genética , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Integr Med ; 18(4): 344-350, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32107172

RESUMO

OBJECTIVE: Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism. METHODS: We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl's staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays. RESULTS: We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats. CONCLUSION: Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

9.
J Biomed Opt ; 25(1): 1-14, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31970943

RESUMO

Significance: As a promising hybrid imaging technique with x-ray excitable nanophosphors, cone-beam x-ray luminescence computed tomography (CB-XLCT) has been proposed for in-depth biological imaging applications. In situations in which the full rotation of the imaging object (or x-ray source) is inapplicable, the x-ray excitation is limited by geometry, or a lower x-ray excitation dose is mandatory, limited view CB-XLCT reconstruction would be essential. However, this will result in severe ill-posedness and poor image quality.

Aim: The aim is to develop a limited view CB-XLCT imaging strategy to reduce the scanning span and a corresponding reconstruction method to achieve robust imaging performance.

Approach: In this study, a group sparsity-based reconstruction method is proposed with the consideration that nanophosphors usually cluster in certain regions, such as tumors or major organs such as the liver. In addition, depth compensation (DC) is adopted to avoid the depth inconsistency caused by a limited view strategy.

Results: Experiments using numerical simulations and physical phantoms with different edge-to-edge distances were carried out to illustrate the validity of the proposed method. The reconstruction results showed that the proposed method outperforms conventional methods in terms of localization accuracy, target shape, image contrast, and spatial resolution with two perpendicular projections.

Conclusions: A limited view CB-XLCT imaging strategy with two perpendicular projections and a reconstruction method based on DC and group sparsity, which is essential for fast CB-XLCT imaging and for some practical imaging applications, such as imaging-guided surgery, is proposed.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Tomografia Computadorizada de Feixe Cônico/instrumentação , Testes Diagnósticos de Rotina , Humanos , Luminescência
10.
Med Phys ; 47(2): 662-671, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31742714

RESUMO

PURPOSE: As a novel imaging modality, x-ray fluorescence computed tomography (XFCT) can provide distribution and concentration information of contrast agents containing high atomic number elements, such as iodine, gadolinium, barium, gold, and platinum. Since XFCT has a better sensitivity and detection limit of high-Z elements compared with traditional and spectral CT, it becomes a powerful quantitative imaging tool for biological studies. The main problem of current XFCT imaging is its low emission and detection efficiency of x-ray fluorescence (XRF) photons. Increasing XRF photons generation by choosing a high atomic element as a contrast agent is essential to improve the imaging quality of XFCT. Gadolinium emits at least a few times more of XRF photons than gold under the same x-ray excitation condition, leading to a detection limit at a level of sub-mg/mL as the next generation of clinical imaging modality. However, most current XFCT studies have utilized gadolinium salt as the contrast agent, which could not accumulate in organs or tumors efficiently, making in vivo XFCT imaging quite difficult. In this study, we present NaGdF4 nanoparticles with ultra-small size as nanoprobes to test the feasibility for in vivo XFCT application for the first time. METHODS: NaGdF4 nanoparticles with different sizes (3-10 nm) were successfully synthesized via a coprecipitation process by controlling the reaction time at temperature of 290 °C. The morphology, crystal phase, chemical composition, and size of such NPs were further characterized with HR-TEM, XRD, and EDX. The abilities of XRF photons from different sizes of NPs were quantified by our customized XFCT imaging system. To access the in vivo application of as-synthesized NPs, such hydrophobic NPs capped OA molecules were further modified with AEP via a ligand-exchange process and characterized with FT-IR. For in vivo XFCT imaging, 0.1 mL of 30 mg/mL NPs were injected into nude mice via the tail vein. The Varian G-297 x-ray tube was set to 150 kV and 0.5 mA. The XRF photons were captured by a Kromek eV-3500 photon counting detector at each 8° for 10 s. RESULT: The successfully synthesized NaGdF4 nanoparticles (3-10 nm) were monodisperse, highly uniform spherical morphology and hexagonal crystalline phases. No significant influence on XRF photons yields or XFCT imaging quality were found by varying the nanoparticle size. The XRF photons were 2.5 times more emitted from NaGdF4 nanoparticles (NPs) compared to gold nanoparticles, thereby leading to a better image quality. With the AEP surface modification, such NPs were readily adapted for use in in vivo XFCT applications with monodispersity in aqueous solution and negligible cytotoxicity. With the tail-vein injection, the liver, spleen, and lungs could be clearly imaged with XFCT at a sub-mg/mL level. CONCLUSIONS: Such NaGdF4 NPs, which were synthesized with coprecipitation process, were modified with AEP for in vivo XFCT applications. With both the phantom and in vivo experiments, such NPs were proved to be appropriate probes for XFCT application with the detection limit at a sub-mg/mL level. In the future research, such NPs could be further functionalized with targeting molecules for early-phase cancer detection.


Assuntos
Meios de Contraste/química , Flúor/química , Gadolínio/química , Nanopartículas Metálicas/química , Espectrometria por Raios X/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Estudos de Viabilidade , Ouro/química , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Nanopartículas Metálicas/administração & dosagem , Camundongos Nus , Tamanho da Partícula , Imagens de Fantasmas , Fótons , Propriedades de Superfície
11.
Int J Mol Sci ; 20(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487880

RESUMO

Pancreatic cancer remains one of the deadliest cancers in the world, as a consequence of late diagnosis, early metastasis and limited response to chemotherapy, under which conditions the potential mechanism of pancreatic cancer progression requires further study. Exosomes are membrane vesicles which are important in the progression, metastasis and chemoresistance in pancreatic cancer. Additionally, they have been verified to be potential as biomarkers, targets and drug carriers for pancreatic cancer treatment. Thus, studying the role of exosomes in pancreatic cancer is significant. This paper focuses on the role of exosomes in the proliferation, metastasis and chemoresistance, as well as their potential applications for pancreatic cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Exossomos/genética , Exossomos/transplante , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia
12.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514451

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas/patologia , Animais , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Genoma , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
13.
Bioconjug Chem ; 30(8): 2191-2200, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31344330

RESUMO

X-ray excited photodynamic therapy (X-PDT), which utilizes X-rays as the energy source and X-ray luminescent nanoparticles (XLNPs) as the transducer to excite photosensitizers (PS), resolves the penetration problem of light in traditional PDT to enable the treatment of deep-seated tumors. Nevertheless, the high X-ray dosage used in X-PDT hampers its potential applications in clinics. In this study, to alleviate the dose problem, ß-NaLuF4:Tb3+ spherical nanoparticles (NPs) with ultrastrong green X-ray excited optical luminescence (XEOL) due to the less nonradiative relaxation probability and high X-ray absorption mass coefficient, which perfectly matches the absorption spectrum of a photosensitizer named rose bengal (RB), were synthesized and employed as the energy transducer for X-PDT. After covalent conjugation of NPs with RB, high Förster resonant energy transfer (FRET) efficiency up to 94.29% was achieved, leading to high production of singlet oxygen. In vivo X-PDT efficacy was evaluated by nude mice with a HepG2 tumor xenograft. With excellent biocompatibility, the synthesized NPs-RB nanocomposite showed significant antitumor efficiency up to 80 ± 12.3% with a total X-ray dose of only 0.19 Gy, demonstrating the feasibility of low-dose X-PDT in vivo for the first time. The present work provides a promising platform for X-PDT in deep-seated tumors.


Assuntos
Nanocompostos/química , Nanopartículas/química , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos da radiação , Raios X , Animais , Linhagem Celular Tumoral , Células Hep G2 , Xenoenxertos , Humanos , Camundongos , Nanopartículas/uso terapêutico , Rosa Bengala
14.
J Neurosurg Spine ; : 1-8, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30835712

RESUMO

OBJECTIVESpinal instability or neurological impairment caused by spinal brown tumors (BTs) with end-stage renal disease (ESRD) is an acute condition that needs urgent surgery. There is not much published information on BTs of the mobile spine given the rarity of the disease, and the literature shows inconsistent treatment options and ambiguous follow-up information. The aim of the present study was to elucidate the clinical features, anesthesia management, and surgical treatment for this rare disease through long-term follow-up observations.METHODSClinical, laboratory, radiological, and perioperative data on 6 consecutive patients with spinal BTs who had been admitted to the authors' institution between 2010 and 2016 were retrospectively reviewed. The literature on spinal BT with secondary hyperparathyroidism was also reviewed. Summaries of the clinical features and anesthesia management are provided.RESULTSThe mean age of the 6 patients was 45.5 years (range 35-62 years). Lesions were located in the cervical segment (2 cases) and thoracic segment (4 cases). Localized pain was the most common complaint, and pathological fracture occurred in 5 patients. Elevation of serum alkaline phosphate (AKP) and parathyroid hormone (PTH) was a common phenomenon. Four patients underwent circumferential resection and 2 underwent laminectomy, with parathyroidectomy performed in all patients. The anesthesia process was uneventful for all patients. The mean follow-up was 33 months (range 26-40 months). No spinal lesion progression occurred in any patient. The Karnofsky Performance Status score improved to 80-90 by 3 months after surgery.CONCLUSIONSAlthough uncommon, spinal BTs should be a diagnostic consideration in patients with ESRD. The thoracic spine is the most frequently affected site. ESRD is not a contraindication for surgery; with the assistance of experienced anesthesiologists, urgent surgery is the preferred option to alleviate neurological impairment and restore spinal stability.

15.
Anal Bioanal Chem ; 411(12): 2663-2674, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30850852

RESUMO

In this work, chemosensors based on mixed ligands were proposed for the cooperative detection of Co2+. The relationship between the specifically selected mixed organic ligands and the detection activities is discussed. Diverse responses to metal ions can be tuned by controlling the structural features of organic ligands, such as different sizes, geometries, substituents, and connectivity. Among the nine investigated systems, DHAB-Tpy, DHAB-Phen, and DHAB-Dpa displayed high selectivity and sensitivity for Co2+, with detection limits of 4.5 × 10-7 M, 1.1 × 10-7 M, and 8.0 × 10-8 M, respectively. The detection of Co2+ was not affected by other metal ions, anions, amino acids, proteins, nucleic acids, lipids and pH conditions. Furthermore, the proposed method was validated in the analysis of Co2+ in real water samples with satisfactory recovery and relative standard deviation values. TAC-Phen and TAC-Dpa could recognize Co2+ qualitatively, but could not detect Co2+ quantitatively. While TAC-Tpy, PAN-Tpy, PAN-Phen, and PAN-Dpa showed no metal ion selectivity. The experimental results were also rationalized by theoretical studies. A mixed ligand system can be used to produce a ratiometric absorption signal to avoid most ambiguities, such as the chemosensor environment and concentration, via self-calibration of two absorption bands. Structural insights derived from detection activities can provide valuable information for the design of new metal ion chemosensors by varying the type of organic ligands. Graphical abstracts The work represents a simple strategy for obtaining synthesis-free, inexpensive, and sensitivity-tunable chemosensors through mixing organic ligands of different sizes, substitutions, geometries, and connectivity to modulate the sensing behaviors.

16.
Biomaterials ; 184: 31-40, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195803

RESUMO

The limitation of light penetration depth invalidates the application of photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X-PDT), which is based on X-rays excited luminescent nanoparticles (XLNP), provides a new strategy for PDT in deep tissues. However, the high X-ray dosage used and non-specific cytotoxicity of the nanoparticle-photosensitizer nanocomposite (NPs-PS) hamper in-vivo X-PDT applications. To address these problems, a simple and efficient NPs-PS nanocomposite using ß-NaGdF4: Tb3+ nanoparticles and widely used PS called Rose Bengal (RB) was designed. With perfectly matched spectrum of NPs emission and RB absorption upon X-ray excitation and covalent conjugation of a large amount of RB on NP surfaces to minimize the energy transfer distance, the system demonstrated ultra-high FRET efficiency up to 99.739%, which leads to maximum production of singlet oxygen for PDT with significantly increased anti-tumor efficacy. By 2-aminoethylphosphonic acid surface modification of NPs, excellent biocompatibility was achieved even at a high concentration of 1 mg/mL. The in-vivo X-PDT efficacy was found around 90% of HepG2 tumor growth inhibition with X-ray dose of only 1.5 Gy, which shows the best anti-tumor efficacy at same X-ray dose level reported so far. The present work provides a promising platform for in-vivo X-PDT in deep tumors.


Assuntos
Gadolínio/química , Nanocompostos/química , Fármacos Fotossensibilizantes/química , Rosa Bengala/química , Térbio/química , Animais , Sobrevivência Celular , Feminino , Transferência Ressonante de Energia de Fluorescência , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Raios X
17.
Onco Targets Ther ; 11: 4609-4619, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122952

RESUMO

Background: CTLA4 is a candidate gene which has been implicated in the development of colorectal cancer (CRC). Patients and Methods: To determine the important role of CTLA-4 polymorphisms on risk of CRC, we genotyped four CTLA-4 tagging polymorphisms and calculated crude/adjusted ORs with their 95% CIs. We recruited 1,003 sporadic CRC cases and 1,303 controls. Results: The findings suggested that CTLA-4 rs231775 G>A polymorphism increased the risk of CRC (homozygote model: adjusted OR=1.40, 95% CI=1.05-1.87, P=0.022; dominant model: adjusted OR=1.19, 95% CI=1.00-1.41, P=0.047; and recessive model: adjusted OR=1.38, 95% CI=1.05-1.82, P=0.021). In a stratified analysis by site of tumor, this association was also found in colon cancer. We also found that CTLA-4 rs231775 GA/AA genotypes might be associated with an increased risk of CRC in Zhenjiang cohort. In addition, we found the CTLA-4 rs16840252 C>T polymorphism was associated with the risk of colon cancer. Haplotype comparison analysis showed that CTLA-4 Grs3087243Crs16840252Crs733618 Ars231775, Grs3087243Crs16840252Trs733618Ars231775, and other haplotypes increased the risk of CRC (P<0.001, <0.001, and 0.002, respectively). Conclusion: This study evidences an association of CTLA-4 tagging polymorphisms and haplotypes with CRC risk. Additional well-designed studies with large sample sizes are required to confirm our findings.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30050590

RESUMO

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer's disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer's disease.

19.
Biochem Biophys Res Commun ; 503(1): 249-256, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-29885833

RESUMO

Malignant melanoma has shown increased incidence and high mortality rate in the last three decades. In this study, we investigated whether combination therapy with ch282-5 (a novel BH3 mimetic) and microwave hyperthermia could display synergistic antitumor effects against melanoma. Our results indicated that combination therapy reduced the viability and proliferation of melanoma cells. Through inhibiting the expression of anti-apoptotic proteins of Bcl-2 and IAP family and activating MAPK proteins, combined hyperthermia enhanced ch282-5-induced apoptosis. Combination therapy also synergistically disturbed the mTOR/p70S6k signaling pathway, which is important for cell survival and migration. Moreover, our results showed that combination therapy remarkably suppressed melanoma cell migration in vitro and significantly reduced experimental pulmonary metastasis in vivo. In conclusion, our results indicate that combination therapy with ch282-5 and hyperthermia has synergistic antitumor effects and provides a possible therapeutic strategy for advanced melanoma.


Assuntos
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/antagonistas & inibidores , Hipertermia Induzida , Melanoma/terapia , Neoplasias Cutâneas/terapia , Animais , Apoptose/efeitos dos fármacos , Biomimética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Terapia Combinada , Gossipol/análogos & derivados , Gossipol/farmacologia , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Masculino , Melanoma/metabolismo , Melanoma/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Micro-Ondas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
20.
Medicine (Baltimore) ; 96(44): e8525, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095314

RESUMO

Early rehabilitation after surgery for patellar fracture is challenging. The purpose of this study was to evaluate the surgical outcome of titanium cable cerclage for patellar fracture in early functional activity.We reviewed a series of 24 patients treated at our hospital with titanium cable. Functional exercises were started early. Patients were followed up for at least 12 months.Fifteen were males and 9 were females. Fracture occurred in the right knee in 13 patients and in the left knee in 11 patients. The most common mode of injury involves a tumble. None of the patients presented with any postoperative complications. The management resulted in satisfactory outcomes.Titanium cable cerclage offers a new strategy in treating patellar fracture.


Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Patela/lesões , Titânio , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Patela/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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