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1.
Nat Chem Biol ; 20(7): 835-846, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38287154

RESUMO

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI. The emergence of PAF and PAF-LPLs in ferroptosis caused the instability of biomembranes and signaled the cell death of neighboring cells. This cascade could be suppressed by PAF-acetylhydrolase (II) (PAFAH2) or by addition of antibodies against PAF. Genetic knockout or pharmacological inhibition of PAFAH2 increased PAF production, augmented synchronized ferroptosis and exacerbated ischemia/reperfusion (I/R)-induced AKI. Notably, intravenous administration of wild-type PAFAH2 protein, but not its enzymatically inactive mutants, prevented synchronized tubular cell death, nephron loss and AKI. Our findings offer an insight into the mechanisms of synchronized ferroptosis and suggest a possibility for the preventive intervention of AKI.


Assuntos
Injúria Renal Aguda , Ferroptose , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Ativação de Plaquetas/metabolismo , Camundongos Knockout , Humanos , Masculino
2.
Small ; : e2405496, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291904

RESUMO

Specifically controlling cell pyroptosis is advantageous for oncotherapy as it allows simultaneous ablation of primary tumors and activation of immunogenicity of tumor environment. Herein, a facile and robust strategy is presented to construct efficient NIR-activated helical pyroptosis agents (PyroAs) with negligible dark cytotoxicity. It is demonstrated that the construction of four intramolecular B-X bonds (X = O or N) within the BODIPY chromophore enforces a significant twisting of its π-conjugation, yielding a variety of helical HBD molecules with desired high photosensitivity and negligible dark toxicity. A robust approach is established to extend HBD into the near-infrared (NIR) region through site-selective incorporation of an electron-withdrawing ester moiety. It is also proved that targeted delivery of the NIR-activated HBD-ER to the endoplasmic reticulum (ER) specifically activates pyroptosis pathway by equipping it with an ER-targeting moiety. Finally, the favorable biocompatibility, excellent antitumor efficacy, and remarkable systematic immune response of this unique NIR-activated helical PyroAs are shown in vivo, demonstrating its potential application in solid tumor immunotherapy.

3.
Langmuir ; 40(39): 20679-20691, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39303170

RESUMO

The introduction of poly(tannic acid) (PTA) and cerium ion [Ce(III)] on the surface of α-zirconium phosphate (α-ZrP) endowed the α-ZrP@PTA-Ce(III)/waterborne epoxy composite coating with enhanced corrosion protection and wear resistance performances. The successful preparation of α-ZrP@PTA-Ce(III) was confirmed through X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectra. PTA improved the compatibility between α-ZrP@PTA-Ce(III) and the waterborne epoxy resin due to the presence of organic groups from tannic acid. The wear resistance test indicated that the incorporation of α-ZrP@PTA-Ce(III) effectively reduced the coefficient of friction and the wear rate. Electrochemical impedance spectroscopy was used to analyze the corrosion protection performance of unbroken coatings and the self-healing ability of scratched coatings. The incorporation of α-ZrP@PTA-Ce(III) improved the protection performace distinctly. In addition, α-ZrP@PTA-Ce(III) endowed the composite coating with dual corrosion inhibition effects, originating from the PTA film, to prevent the penetration of corrosive media and a dense film that came from the Ce(III) cation. The waterborne epoxy system with enhanced corrosion and wear resistance in this paper broadens the application of α-ZrP.

4.
Langmuir ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019028

RESUMO

The use of graphene-based materials as anticorrosion coatings to protect metals is always a topic of discussion. In this work, silicon nitride (Si3N4) was aminated to improve its water dispersibility. Then it is attached to the graphene oxide (GO) surface to improve compatibility with epoxy (EP) resin as well as conductivity. The results of Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and zeta potentials test analyses indicated that Si3N4-NH2@GO with a layer-point structure has been successfully prepared. The corrosion resistance of the composite coatings was characterized by electrochemical impedance spectroscopy (EIS) and polarization curve analysis, and the wear resistance of the composite coatings was tested by friction and wear tests. The results showed that 1.0% Si3N4-NH2@GO has excellent corrosion and wear resistance. The use of Si3N4-NH2@GO layer point structures in this study broadens the way for GO applications.

5.
Langmuir ; 40(22): 11817-11827, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38760325

RESUMO

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

6.
Asia Pac J Clin Nutr ; 33(4): 529-538, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39209362

RESUMO

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Patients with GC have higher nutritional risk. This study aimed to construct a nomogram model for predicting preoperative nutritional risk in patients with GC in order to assess preoperative nutritional risk in patients more precisely. METHODS AND STUDY DESIGN: Patients diagnosed with GC and undergoing surgical treatment were included in this study. Data was collected through clinical information, laboratory testing, and radiomics-derived characteristics. Least absolute shrinkage selection operator (LASSO) regression analysis and multi-variable logistic regression were employed to construct a clinical prediction model, which takes the form of a logistic nomogram. The effectiveness of the nomogram model was evaluated using receiver operat-ing characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of three predictors, namely body mass index (BMI), hemoglobin (Hb) and radiomics characteristic score (Radscore) were identified by LASSO regression analysis from a total of 21 variables studied. The model constructed using these three predictors displayed medium prediction ability. The area under the ROC curve was 0.895 (95% CI 0.844-0.945) in the training set, with a cutoff value of 0.651, precision of 0.957, and sensitivity of 0.718. In the validation set, it was 0.880 (95% CI 0.806-0.954), with a cutoff value of 0.655, precision of 0.930, and sensitivity of 0.698. DCA also confirmed the clinical benefit of the combined model. CONCLUSIONS: This simple and dependable nomogram model for clinical prediction can assist physicians in assessing preoperative nutritional risk in GC patients in a time-efficient and accurate manner to facilitate early identification and diagnosis.


Assuntos
Nomogramas , Estado Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Adulto , Curva ROC , Índice de Massa Corporal
7.
J Am Chem Soc ; 144(14): 6208-6214, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35357829

RESUMO

Here, we report on a new kind of compound, XδIr4X12-δ (X = P, As), the first hole-doped skutterudites superconductor. We provide atomic-resolution images of the caging As atoms using scanning transmission electron microscopy (STEM). By inserting As atoms into the caged structure under a high pressure, superconductivity emerges with a maximum transition temperature (Tc) of 4.4 K (4.8 K) in IrAs3 (IrP3). In contrast to all of the electron-doped skutterudites, the electronic states around the Fermi level in XδIr4X12-δ are dominated by the caged X atom, which can be described by a simple body-centered tight-binding model, implying a distinct pairing mechanism. Our density functional theory (DFT) calculations reveal an intimate relationship between the pressure-dependent local-phonon mode and the enhancement of Tc. The discovery of XδIr4X12-δ provides an arena to investigate the uncharted territory of hole-doped skutterudites, and the method proposed here represents a new strategy of carrier doping in caged structures, without introducing extra elements.

8.
Clin Genet ; 101(1): 101-109, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34671977

RESUMO

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.


Assuntos
Sequenciamento do Exoma , Estudos de Associação Genética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Unidades de Terapia Intensiva Neonatal , Alelos , China , Mapeamento Cromossômico , Variações do Número de Cópias de DNA , Feminino , Estudos de Associação Genética/métodos , Testes Genéticos , Humanos , Mutação INDEL , Masculino , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma
9.
BMC Cancer ; 22(1): 1154, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36348289

RESUMO

BACKGROUND: The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. PATIENTS AND METHODS: Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. RESULTS: Multivariate analysis showed that the surgical procedure (P < 0.001), period of chemotherapy (P < 0.001), T stage (P = 0.006), N stage (P = 0.040), systemic immune-inflammatory index (SII) (P < 0.001), and fibrinogen level (P = 0.026) were independent factors affecting OS. The nomogram constructed on the aforementioned factors for predicting the 1- and 3-year OS achieved a Harrell's concordance index (C-index) of 0.756 and 0.763 for the training and verification cohorts, respectively. Compared with the 8th American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM) staging system, the nomogram had higher C-index values and areas under the curve (AUCs) and slightly higher net clinical benefit. CONCLUSION: Compared to the 8th AJCC staging system, the newly developed nomogram showed superior performance in predicting the survival of GC patients with GOO after gastrectomy.


Assuntos
Obstrução da Saída Gástrica , Neoplasias Gástricas , Humanos , Nomogramas , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , China/epidemiologia , Prognóstico , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Estadiamento de Neoplasias
10.
J Am Chem Soc ; 143(18): 7042-7049, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33926192

RESUMO

The charge, spin, and composition degrees of freedom in a high-entropy alloy endow it with tunable valence and spin states, infinite combinations, and excellent mechanical performance. Meanwhile, the stacking, interlayer, and angle degrees of freedom in a van der Waals material bring to it exceptional features and technological applications. Integration of these two distinct material categories while keeping their merits would be tempting. On the basis of this heuristic thinking, we design and explore a new range of materials (i.e., dichalcogenides, halides, and phosphorus trisulfides) with multiple metallic constitutions and intrinsic layered structure, which are coined as high-entropy van der Waals materials. Millimeter-scale single crystals with a homogeneous element distribution can be efficiently acquired and easily exfoliated or intercalated in this materials category. Multifarious physical properties such as superconductivity, magnetic ordering, metal-insulator transition, and corrosion resistance have been exploited. Further research based on the concept of high-entropy van der Waals materials will enrich the high-throughput design of new systems with intriguing properties and practical applications.

11.
Small ; 17(29): e2101180, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34145754

RESUMO

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen (1 O2 ) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self-limiting. Herein, a sophisticated photosensitive polymeric material (An-NP) that allows sustained 1 O2 generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates 1 O2 , An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing 1 O2 with superior reversibility and a dye J-aggregate with superb photothermal performance. Thus, in 655 nm laser-triggered PDT process, An-NP generates abundant 1 O2 with extra 1 O2 being trapped via the conversion into EPO-NP; while in the subsequent 785 nm laser-driven PTT process, the converted EPO-NP undergoes thermolysis to liberate the captured 1 O2 and regenerates An-NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate 1 O2 . The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor-bearing mice, respectively.


Assuntos
Fotoquimioterapia , Oxigênio Singlete , Animais , Linhagem Celular Tumoral , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia
13.
Anal Chem ; 92(15): 10792-10799, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32648733

RESUMO

Endowing fluorogenic probes with ultrahigh contrast is essential to increasing the accuracy of fluorescence sensing and imaging. Phenolate-based D-π-A fluorophores (A-DOH) belong to a big family of fluorophores and have attracted increasing attention in fluorogenic probe design. However, the intrinsic dilemma of weak intracellular emission of traditional A-DOH fluorophores resulted in low contrast during live cell imaging. Herein, we present a general and robust approach to preparing novel A-DOH fluorophores with bright NIR fluorescence in living cells based on the unique halogen effects. The reported chlorinated A-DOH fluorophore (A1-2ClOH) has an extremely strong fluorescence in an aqueous solution of pH 7.4 and living cells, which is 194 and 30 times higher than that of the traditional halogen-free analogue (A1-OH), respectively. We systematically investigated and demonstrated that the distinct -I and +M halogen effects, which led to a drastic decrease in the pKa value and a significant enhancement in the fluorescence quantum yield, respectively, should be responsible for the tremendous fluorescence enhancement. The flexible phenol caging chemistry allows one to prepare multiple NIR fluorogenic probes based on the A1-2ClOH scaffold with high contrast for live cell imaging of a variety of analytes by introducing a corresponding triggering moiety. Moreover, the conjugated azide group of A1-2ClOH enables the integration of more functions as desired through a facile click reaction. A fluorogenic probe (mitoProbe-PN) was synthesized as a paradigm by equipping the A1-2ClOH scaffold with a mitochondria-targeting moiety and a peroxynitrite-responsive triggering group and demonstrated specific high-contrast fluorescence imaging of endogenous OONO- in mitochondria of living macrophages.


Assuntos
Corantes Fluorescentes/química , Halogênios/química , Raios Infravermelhos , Linhagem Celular Tumoral , Corantes Fluorescentes/metabolismo , Halogênios/metabolismo , Humanos , Mitocôndrias/metabolismo , Ácido Peroxinitroso/química
14.
Chemistry ; 26(20): 4505-4509, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32077546

RESUMO

Dye assemblies exhibit fascinating properties and performances, both of which depend critically on the mutual packing arrangement of dyes and on the supramolecular architecture. Herein, we engineered, for the first time, an intriguing chlorosome-mimetic 2D crystalline J-dimer lamellar structure based on halogenated dyes in aqueous media by employing two distinct orthogonal halogen-bonding (XB) interactions. As the only building motif, antiparallel J-dimer was formed and stabilized by single π-stacking and dual halogen⋅⋅⋅π interactions. With two substituted halogen atoms acting as XB donors and the other two acting as acceptors, the constituent J-dimer units were linked by quadruple highly-directional halogen⋅⋅⋅halogen interactions in a staggered manner, resulting in unique 2D lamellar dye assemblies. This work champions and advances halogen-bonding as a remarkably potent tool for engineering dye aggregates with a controlled molecular packing arrangement and supramolecular architecture.

15.
World J Surg ; 44(5): 1666-1672, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31915978

RESUMO

BACKGROUND: Blunt cardiac injury (BCI) increases with traffic accidents and is an important cause of death in trauma patients. In particular, for patients who need surgical treatment, the mortality rate is extremely high unless the patient is promptly operated on. This study aimed to explore early recognition and expeditious surgical intervention to increase survival. METHODS: All patients with BCIs during the past 15 years were reviewed, and those who underwent operative treatment were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. RESULTS: A total of 348 patients with BCIs accounted for 18.3% of 1903 patients with blunt thoracic injury (BTI). Of 348 patients, 43 underwent operative treatment. The main cause of injury was traffic accidents, with an incidence of 48.8%. Of them, steering wheel injuries occurred in 15 patients. In 26 patients, a preoperative diagnosis was obtained by echocardiography, CT scanning, etc. In the remaining 17, who had to undergo urgent thoracotomy without any preoperative imaging, a definitive diagnosis of BCI was proven during the operation. The volume of preoperative infusion or crystalloid was <1000 ml in 31 cases. Preoperative pericardiocentesis was not used in anyone. In 12 patients, the operation commenced within 1 h. Overall mortality was 32.6%. The death was caused by BCI in 9. CONCLUSIONS: Facing a patient with BTI, a high index of suspicion for BCI must be maintained. To manage those requiring operations, early recognition and expeditious thoracotomy are essential. Preoperatively, limited fluid resuscitation is emphasized. We do not advocate preoperative pericardiocentesis.


Assuntos
Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/cirurgia , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/cirurgia , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Emergências , Feminino , Traumatismos Cardíacos/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Toracotomia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/etiologia , Adulto Jovem
16.
J Am Chem Soc ; 141(1): 402-413, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30547576

RESUMO

Controlling the packing arrangements of dyes is a facile way of tuning their photophysical and/or photochemical properties, thus enabling new sensing mechanisms for photofunctional tools. Here, we present a general and robust strategy toward water-stable J-aggregated dye-templated nanoassemblies by incorporating an amphiphilic diblock copolymer and a stimuli-responsive dye as the only two building components. An iodo-substituted boron dipyrromethene (BODIPY) was adopted as a template to direct the self-assembly of poly(ethylene glycol)- block-polycaprolactone (PEG-PCL), forming a core-shell nanoplate with slip-stacked BODIPYs as core surrounded by hydrophilic PEG shell. The self-assembled nanoplate is stable in cell culture medium and possesses a built-in stimuli-responsiveness that arises from BODIPY bearing meso-carboxylate protecting group, which is efficiently removed upon treatment with peroxynitrite. The resulting negative charges lead to rearrangement of dyes from J-stacking to nonstacking, which activates photoinduced singlet oxygen production from the nanoassemblies. The stimuli-activatable photosensitivity has been exploited for specific photodynamic ablation of activated RAW 264.7 cells with excessive endogenous peroxynitrite. In light of the generality of the sensing mechanism, the concept described herein will significantly expand the palette of design principles to develop diverse photofunctional tools for biological research and clinical needs.


Assuntos
Corantes/química , Nanoestruturas/química , Compostos de Boro/química , Interações Hidrofóbicas e Hidrofílicas , Lactonas/química , Modelos Moleculares , Conformação Molecular , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química
17.
Angew Chem Int Ed Engl ; 58(46): 16601-16609, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31469219

RESUMO

Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long-wavelength D-π-A photosensitizer, PSSe-I , with highly efficient photosensitivity for generation of 1 O2 was used. Caging of the phenolate donor of PSSe-I with a biomarker-sensitive group provided ALP PS, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito-PN PS, equipped with a mitochondria-targeting group and a specific peroxynitrite-reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.


Assuntos
Luz , Fármacos Fotossensibilizantes/química , Animais , Azidas/química , Biomarcadores/química , Sobrevivência Celular/efeitos dos fármacos , Fluoresceínas/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ácido Peroxinitroso/química , Fármacos Fotossensibilizantes/farmacologia , Células RAW 264.7 , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
18.
J Med Genet ; 54(10): 685-692, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28705883

RESUMO

BACKGROUND: Copy number variation (CNV) is a valuable source of genetic diversity in the human genome and a well-recognised cause of various genetic diseases. However, CNVs have been considerably under-represented in population-based studies, particularly the Han Chinese which is the largest ethnic group in the world. OBJECTIVES: To build a representative CNV map for the Han Chinese population. METHODS: We conducted a genome-wide CNV study involving 451 male Han Chinese samples from 11 geographical regions encompassing 28 dialect groups, representing a less-biased panel compared with the currently available data. We detected CNVs by using 4.2M NimbleGen comparative genomic hybridisation array and whole-genome deep sequencing of 51 samples to optimise the filtering conditions in CNV discovery. RESULTS: A comprehensive Han Chinese CNV map was built based on a set of high-quality variants (positive predictive value >0.8, with sizes ranging from 369 bp to 4.16 Mb and a median of 5907 bp). The map consists of 4012 CNV regions (CNVRs), and more than half are novel to the 30 East Asian CNV Project and the 1000 Genomes Project Phase 3. We further identified 81 CNVRs specific to regional groups, which was indicative of the subpopulation structure within the Han Chinese population. CONCLUSIONS: Our data are complementary to public data sources, and the CNV map may facilitate in the identification of pathogenic CNVs and further biomedical research studies involving the Han Chinese population.


Assuntos
Povo Asiático/genética , Variações do Número de Cópias de DNA , Etnicidade/genética , Variação Genética , Genoma Humano , China , Humanos , Masculino
19.
J Craniofac Surg ; 29(5): 1338-1340, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29608485

RESUMO

OBJECTIVE: Spasmodic torticollis (ST) is an idiopathic neurologic disorder affecting the muscles of the neck. Surgery is a preferred treatment, when conservative treatments or Botulinum neurotoxin injections fail to relieve the symptoms. Our objective here is to report the outcome of a new surgical method for treating ST patients in our department. METHODS: The new procedure consists of rhizotomy of the spinal accessory nerve (SAN) and C1-C2 nerve roots, coagulation of the distal end of SAN (Group A). The results of this procedure were compared with a group of patients who underwent only rhizotomy of the SAN and anterior C1-C2 nerve roots (Group B). Clinical data were retrospectively collected from 39 patients with laterocollis and rotatory torticollis subtypes of ST from Jun 1, 2014 to Jun 1, 2015. The effect of the surgery was evaluated by the reduction in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores preoperatively and postoperatively. The mean duration of the postoperative follow-up period was 2.57 years, ranging from 2 to 3 years. RESULTS: The mean preoperative TWSTRS score was 65.89 ±â€Š3.55 and 65.80 ±â€Š3.45 in Groups A and B, respectively. Six months after the surgery, the TWSTRS scores decreased to 40.00 ±â€Š12.14 and 26.04 ±â€Š11.77, respectively. There was a statistically significant improvement preoperatively and postoperatively in both groups (P < 0.05). The decrease in TWSTRS score of Group B was more significant than that of Group A (P < 0.05). The main complications included shoulder numbness, shoulder weakness, and hoarseness. CONCLUSIONS: The procedure in this study provides a new and effective surgical method for patients with ST. This procedure should be recommended if conservative therapy does not offer satisfactory relief of symptoms.


Assuntos
Nervo Acessório/cirurgia , Eletrocoagulação , Rizotomia/métodos , Raízes Nervosas Espinhais/cirurgia , Torcicolo/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Cell Tissue Bank ; 19(1): 35-46, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28815373

RESUMO

Cell based tissue engineering serves as a promising strategy for articular cartilage repair, which remains a challenge both for researchers and clinicians. The aim of this research was to assess the potential of autologous nasal chondrocytes (NCs) combined with alginate hydrogel as injectable constructs for rabbit articular cartilage repair. Autologous nasal chondrocytes were isolated from rabbit nasal septum, expanded either on monolayer or in 3D alginate hydrogel. In vitro, DNA quantification revealed that NCs can proliferate stable in 3D alginate matrix, but slower than that cultured in monolayer. Further, a higher synthesis rate of glycosaminoglycans (GAGs) was detected by GAG measurement in 3D alginate culture. Gene expression analysis at different time point (day 1, 7, 14) showed that 3D culture of NCs in alginate up-regulated chondrogenic markers (Col2A1, ACAN SOX9), meanwhile down-regulated dedifferentiation related gene (Col1A1). In vivo, autologous nasal chondrocytes combined with alginate hydrogel were used for repairing rabbit knee osteochondral defect (Alg + NC group). Histological staining indicated that Alg + NC group obtained superior and more hyaline-like repaired tissue both at 3 and 6 months after surgery. Mechanical analysis showed that the repaired tissue in the Alg + NC group possessed similar mechanical properties to the native cartilage. In conclusion, nasal chondrocytes appeared to be a very promising seed cell source for cartilage tissue engineering, and alginate hydrogel can serve as suitable delivery system.


Assuntos
Cartilagem Articular/fisiologia , Condrócitos/transplante , Hidrogéis/química , Septo Nasal/citologia , Regeneração , Alicerces Teciduais/química , Alginatos/administração & dosagem , Animais , Cartilagem Articular/citologia , Separação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese , Ácido Glucurônico/administração & dosagem , Ácidos Hexurônicos/administração & dosagem , Hidrogéis/administração & dosagem , Injeções , Coelhos , Engenharia Tecidual
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