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1.
Colloids Surf B Biointerfaces ; 234: 113697, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38071945

RESUMO

Benefiting from the biocompatibility, adhesiveness, and natural extracellular matrix-mimicking ability, hydrogels have received increasing research in recent years. In this study, a hydrogel system composed of dopamine, quaternized ammoniated chitosan (QCS), and polyvinylpyrrolidone was reported to exhibit fast hemostatic properties in Sprague-Dawley rat tail amputation and liver bleeding models. The results showed that this hydrogel had good hemostatic properties. The designed hydrogel showed high swelling ratios in H2O, PBS, and 0.9 % NaCl solution, indicating its capability to absorb tissue residual exudate and form a stable hydrogel. Compared with the control group, the blood loss in Sprague-Dawley rat tail amputation and liver bleeding were reduced by nearly 78 % and 76 %, respectively. Interestingly, dopamine endowed the hydrogel with antioxidant properties, thus holding a great application promise in inflammatory wounds. Furthermore, the designed hydrogel demonstrated good and reversible adhesion properties (12.23 ± 0.22 kPa-24.31 ± 0.55 kPa), ensuring its firm attachment to bleeding wounds of pig skin in wet environments. This research points out a novel path for designing chitosan-based hydrogels for biomedical applications.


Assuntos
Quitosana , Hemostáticos , Ratos , Animais , Suínos , Quitosana/farmacologia , Antioxidantes/farmacologia , Hidrogéis/farmacologia , Dopamina , Ratos Sprague-Dawley , Aderências Teciduais , Hemostáticos/farmacologia , Hemostasia , Antibacterianos
2.
BMJ Open ; 13(6): e069702, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344116

RESUMO

OBJECTIVES: To investigate incident cataract surgery and to investigate determinants of cataract surgery uptake in Chinese adults. DESIGN: This nationally representative longitudinal study recorded self-reported incident cataract surgery, and measured biological, clinical and socioeconomical characteristics at baseline and endline. SETTING: In the first stage, 150 county-level units were randomly chosen with a probability-proportional-to-size sampling technique from a sampling frame containing all county-level units. The sample was stratified by region and within region by urban district or rural county and per capita gross domestic product. The final sample of 150 counties fell within 28 provinces of China. PARTICIPANTS: Urban and rural Chinese persons aged 45 years and older. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident cataract surgery (primary outcome) and the factors associated with incident cataract surgery (secondary outcome). RESULTS: Among 16 663 people enrolled in 2011, 13 705 (82.2%) attended follow-up in 2015. Among these, 167 (1.22%) reported incident cataract surgery. Those receiving surgery were significantly older (66.2±8.79 vs 58.3±9.18, p≤0.001) and more likely to report: illiteracy (44.9% vs 27.1%, p<0.001), poor baseline distance vision (49.7% vs 20.0%, p≤0.001), poor baseline near vision (37.1% vs 21.8%, p≤0.001), baseline visual impairment (15.6% vs 5.5%, p≤0.001), diabetes (12.0% vs 7.42%, p≤0.05) and higher baseline depression scores (9.7 vs 8.4 on a scale of 0-30, p≤0.05). In linear regression models, older age, worse distance vision, hypertension or diabetes, illiteracy and lower depression score were significantly associated with undergoing surgery. Results were similar in models including only persons aged ≥60 years, except that urban residence was also associated with surgery. When only those aged ≥60 years with poor vision were included, results were again the same, except that higher household expenditure was also associated with surgery. CONCLUSIONS: In China, cataract surgical rates remain low; underserved groups such as rural dwellers are less likely to receive cataract surgery.


Assuntos
Extração de Catarata , Catarata , Baixa Visão , Humanos , Estudos Longitudinais , Acuidade Visual , Catarata/epidemiologia , China/epidemiologia
3.
Global Spine J ; 13(5): 1311-1318, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34263657

RESUMO

STUDY DESIGN: Retrospective analysis. OBJECTIVE: We investigated whether complete correction of cervical sagittal malalignment is necessary during 4-level anterior cervical discectomy and fusion (ACDF) in patients with kyphosis. METHODS: This retrospective study included 84 patients who underwent 4-level ACDF surgery at a university hospital between January 2010 and December 2015. Based on the degree of cervical lordosis correction, patients were categorized into the following groups: mild (0-10°), moderate (10-20°), and complete correction (>20°). The clinical outcomes, radiological parameters, and functional outcomes were analyzed. RESULTS: We observed no significant intergroup differences in the baseline characteristics. The cervical sagittal vertical axis (CSVA) correction loss at the final follow-up was lesser in the mild- and moderate- than in the complete-correction group. The spinocranial angle (SCA) and T1 slope (T1 S) were significantly higher in the moderate- and complete-correction groups than in the mild-correction group, 3 days postoperatively. The cervical proximal junctional kyphosis (CPJK), adjacent segment degeneration (ASD), and ASD following CPJK rates were higher in the complete-correction group. We observed no significant intergroup differences in postoperative complications; however, 5 patients showed internal fixation failure in the complete-correction group; 4 of these patients required reoperation. No significant intergroup difference was observed in the Japanese Orthopedic Association and neck disability index scores at any time point. CONCLUSIONS: A mild-to-moderate correction of cervical lordosis is superior to complete correction in patients with kyphosis who undergo 4-level ACDF because this approach is associated with lesser axial stress and CSVA correction loss.

4.
J Cosmet Dermatol ; 21(11): 6363-6376, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35947513

RESUMO

OBJECTIVE: To explore the potential mechanism of complex rose-bergamot essential oil against anxiety accompanied with facial spots through network pharmacology. METHODS: The components of rose and bergamot essential oils were determined by GC-MS and obtained from literature, and their action targets were predicted by PubChem, SwissADME and SwissTargetPrediction databases. Using "Anxiety disorder" and "Facial pigmentation" as keywords, the relevant targets of anxiety disorder and facial spots were mined in the databases of DrugBank, TTD, GeneCards, and OMIM. The intersection targets of complex rose-bergamot essential oil and anxiety accompanied with facial spots diseases were obtained by making Venn diagram, respectively. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersection targets were carried out through STRING platform, Metascape, and KEGG Mapper databases. The "complex essential oil- component- target- pathway" network was constructed by Cytoscape software. The key active compounds and core targets were docked by AutoDock software. RESULTS: A total of 34 active components of complex rose-bergamot essential oil and 405 corresponding targets were obtained. The intersection targets of complex essential oil with anxiety disorder and facial spot were 88 and 34, respectively, and the related KEGG pathways were 137 and 123 items, respectively. Neroli acetate, Neroli alcohol, and Linalool in complex rose-bergamot essential oil could play a therapeutic role in anxiety disorder by regulating key targets such as SLC6A4, GRIN2B and DRD2 to participate in the neuroactive ligand-receptor interaction and serotonergic synapse and other pathways, they also could play a role in the treatment of facial spots by regulating key targets such as EGFR, VEGFA, and PIK3CA in the PI3K-AKT, JAK-STAT and other signal pathways. The molecular docking between the key compounds and the core targets showed that the binding energy was less than 0 kcal /mol, indicating that the compound and the target could bind stably. CONCLUSION: Complex rose-bergamot essential oil can play a role in the treatment of anxiety disorder with facial spots through the synergistic mechanism of multicomponent, multitarget, and multipathway.


Assuntos
Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Ansiedade , Proteínas da Membrana Plasmática de Transporte de Serotonina
5.
Front Cell Dev Biol ; 10: 834620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300407

RESUMO

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

6.
Global Spine J ; 12(4): 620-626, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32975454

RESUMO

STUDY DESIGN: This was a prospective controlled study. OBJECTIVE: To compare the accuracy and clinical outcomes of robot-assisted (RA) and fluoroscopy-guided (FG) pedicle screw placement in posterior cervical surgery. METHODS: This study included 58 patients. The primary outcome measures were the 1-time success rate and the accuracy of pedicle screw placement according to the Gertzbein-Robbins scales. The secondary outcome measures, including the operative time, intraoperative blood loss, hospital stay, cumulative radiation time, radiation dose, intraoperative advent events, and postoperative complications, were recorded and analyzed. The Japanese Orthopedics Association (JOA) scores and Neck Disability Index (NDI) were used to assess the neurological function of patients before and at 3 and 6 months after surgery. RESULTS: The rate of grade A was significantly higher in the RA group than in the FG group (90.6% and 71.1%; P < .001). The clinically acceptable accuracy was 97.2% in the RA group and 90.7% in the FG group (P = .009). Moreover, the 1-time success rate was significantly higher in the RA group than in the FG group. The RA group had less radiation time (P < .001) and less radiation dose (P = .002) but longer operative time (P = .001). There were no significant differences in terms of intraoperative blood loss, hospital stay, intraoperative adverse events, postoperative complications, JOA scores, and NDI scores at each follow-up time point between the 2 groups. CONCLUSIONS: The RA technique achieved higher accuracy and 1-time success rate of pedicle screw placement in posterior cervical surgery while achieving comparable clinical outcomes.

7.
Global Spine J ; 12(4): 579-587, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32985251

RESUMO

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of percutaneous transforaminal endoscopic decompression (PTED) for lumbar stenosis associated with adult degenerative scoliosis and to analyze the correlation between preoperative radiological parameters and postoperative surgical outcomes. METHODS: Two years of retrospective data was collected from 46 patients with lumbar stenosis associated with adult degenerative scoliosis who underwent PTED. The visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria were used to evaluate the clinical outcomes. Multiple linear regression analysis was used to analyze the correlation between radiological parameters and surgical outcomes. RESULTS: The mean age of the 33 female and 13 male patients was 73.5 ± 8.1 years. The mean follow-up was 27.6 ± 3.5 months (range from 24 to 36). The average coronal Cobb angle was 24.5 ± 8.2°. There were better outcomes of the VAS for leg pain and Oswestry Disability Index after surgery. Based on the MacNab criteria, excellent or good outcomes were noted in 84.78% of patients. Multiple linear regression analysis showed that Cobb angle and lateral olisthy may be the predictors for low back pain. CONCLUSION: Transforaminal endoscopic surgery may be an effective and safe method for geriatric patients with lumbar stenosis associated with degenerative scoliosis. The predictive factors of clinical outcomes were severe Cobb angle and high degree lateral subluxation. Transforaminal endoscopic surgery may not be recommended for patients with Cobb angle larger than 30° combined with lateral subluxation.

8.
J Anim Physiol Anim Nutr (Berl) ; 106(3): 485-493, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34494310

RESUMO

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.


Assuntos
Altitude , Proteômica , Adaptação Fisiológica , Animais , Bovinos , Genoma , Proteoma
9.
J Endocrinol ; 250(1): 13-24, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34014834

RESUMO

Estrogen receptors (ERs) regulate the development of the growth plate (GP) by binding to estrogen, a phenomenon that determines the growth of skeletal bone. However, the exact mechanisms underlying the regulatory effects of ERs on axial and appendicular growth plates during puberty remain unclear. In the present study, the strategy of ERß blocking resulted in increased longitudinal elongation of the appendicular bone (P < 0.01), whereas ERα blocking suppressed appendicular elongation (P < 0.05). Blocking both ERs did not have opposite effects on axial longitudinal growth. The expression of chondrocyte proliferation genes including collagen II, aggrecan, and Sox9 and hypertrophic marker genes including collagen X, MMP13, and Runx2 was significantly increased in the growth plate of female mice treated with ERß antagonist compared with that in the GP of control mice (P < 0.05). There were no significant differences in local insulin-like growth factor 1 (IGF-1) expression among these groups (P > 0.05), and Indian hedgehog protein (Ihh) and parathyroid-related protein (PTHrP) expressions differed among these groups (P < 0.05). ERs appeared not to affect axial bone growth during puberty in female mice (P > 0.05). Our data show that the blocking of different ER subtypes might have a region-specific influence on longitudinal appendicular and axial growth.


Assuntos
Desenvolvimento Ósseo , Receptores de Estrogênio/metabolismo , Animais , Condrócitos/fisiologia , Feminino , Camundongos Endogâmicos C57BL , Piperidinas , Pirazóis , Pirimidinas , Distribuição Aleatória , Maturidade Sexual
10.
Clin Neurol Neurosurg ; 202: 106524, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33578228

RESUMO

OBJECTIVE: Recovery of hand motor function after surgical treatment in myelopathy patients is commonly observed. Accurate evaluation of postoperative hand function contributes to assessing the efficacy of surgical treatment. However, no objective and effective evaluation method has been widely accepted in clinical practice. Therefore, the study aimed to explore the value of Myelopathy-hand Functional Evaluation System (MFES) in assessing the postoperative hand function for myelopathy patients. MATERIAL AND METHOD: MFES mainly consist of a pair of wise-gloves and a computer with software. One hundred and thirty myelopathy patients were included and all of them received optimal surgery treatment. The Japanese Orthopaedic Association (JOA) scores were marked at preoperative and at 6 months after surgery. All patients were asked to perform the 10-s grip and release test, and the hand movements were simulated and converted into waveforms by MFES. The waveform parameters were measured and analyzed. RESULTS: The JOA scores and the number of grip-and-release (G-R) cycles significantly increased after surgery. Correspondingly, the waveforms of ulnar three fingers were significantly higher and narrower, along with the significantly declined average time per cycle in postoperative. The a/b ratio (Wave height/wave width) of five fingers were significantly higher in postoperative than that in preoperative. Based on the improvement rate of a/b, the excellent and good rate of surgical outcomes was 62.30 %, which was significantly higher than that (47.69 %) based on the improvement rate of JOA scores (P = 0.019). CONCLUSION: MFES is an effective assessment tool in evaluating the postoperative hand function for myelopathy patients.


Assuntos
Força da Mão/fisiologia , Mãos/fisiopatologia , Desempenho Físico Funcional , Compressão da Medula Espinal/cirurgia , Fusão Vertebral , Espondilose/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/cirurgia , Discotomia , Feminino , Humanos , Laminectomia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Compressão da Medula Espinal/fisiopatologia , Espondilose/fisiopatologia , Resultado do Tratamento
11.
J Thorac Cardiovasc Surg ; 161(4): 1266-1271, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31767359

RESUMO

OBJECTIVE: To investigate a technical method for harvesting and using the descending branch of the lateral circumflex femoral artery (DLCFA) in coronary artery bypass grafting (CABG). METHODS: Between January 2017 and January 2019, 40 patients (36 in the planed selection group and 4 in the temporary decision group) with mean age of 49.1 ± 7.5 years received DLCFA as an arterial conduit in CABG. In all patients, the DLCFA was successfully harvested via an anterior thigh incision. Depending on the location of the target vessel, the DLCFA was used as a free graft or a composite graft. RESULTS: Of the 44 patients in the planned selection group, DLCFA harvesting was abandoned in 8 patients because computed tomographic angiography revealed anatomical variation or stenosis of the superficial femoral artery. Of the 5 patients in the temporary decision group, harvesting was abandoned in 1 because of short length and thin caliber. On an average, 3.7 ± 0.9 distal anastomoses were created during CABG, with no adverse effects. The length of the harvested DLCFA was 9.9 ± 1.7 cm, with an average proximal lumen diameter of 3.4 ± 0.7 mm. The DLCFA was used as a free graft in 26 patients and as a "Y"-shape composite graft in 14 patients. Total arterial CABG was performed in 75% of the patients. CONCLUSIONS: The DLCFA is an alternative conduit for CABG. It can be harvested easily and safely. However, preoperative computed tomographic angiography examination is necessary for the smooth application of the DLCFA, and an appropriate strategy for graft establishment should be considered.


Assuntos
Ponte de Artéria Coronária/métodos , Artéria Femoral/transplante , Adulto , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade
12.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5184-5192, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350234

RESUMO

Ginsenoside Rg_3 is widely used in clinical practice as an anti-tumor adjuvant drug, but its application is limited due to its poor oral absorption. In this study, we intended to construct a ginsenoside Rg_3 nanostructured lipid carrier modified by the pullulan(PUL-Rg_3-NLC) to improve the adhesion properties of ginsenoside Rg_3, promote the drug uptake and improve the anti-tumor efficacy. PUL-Rg_3-NLC was characterized by morphology, particle size and Zeta potential. In vivo adhesion characteristics were evaluated by oral gavage tests, and the results were verified from multiple perspectives in combination with in vitro uptake behavior and in vitro pharmacodynamics. The results showed that PUL-Rg_3-NLC, with a particle size of(102±1.89) nm, was characterized by gastric adhesion and could be retained in gastric tissues for a long time, and its uptake by BGC-823 cells was promoted mainly through the pathway mediated by the caveolin-mediated endocytosis. In vitro MTT, cell apoptosis, wound-healing assay and invasion assay all showed some anti-tumor effects. Therefore, PUL-Rg_3-NLC can significantly promote the adhesion of Rg_3 in the stomach, promote the uptake of drugs by gastric cancer cells, and improve the anti-tumor effect. This study can provide some reference for the adjuvant treatment of gastric cancer.


Assuntos
Ginsenosídeos , Nanoestruturas , Portadores de Fármacos , Glucanos , Lipídeos , Tamanho da Partícula
15.
Exp Ther Med ; 19(2): 1417-1424, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010317

RESUMO

The efficacy of fusion combined with decompression for the treatment of spinal stenosis with degenerative lumbar spondylolisthesis (DLS) has been debated. Percutaneous transforaminal endoscopic decompression (PTED) under local anesthesia is an ultra-minimally invasive procedure. The present study aimed to evaluate whether PTED is an effective alternative therapy for spinal stenosis associated with DLS in elderly patients. PTED was performed in elderly patients exhibiting lumbar stenosis and low-grade (Meyerding grades I and II) DLS; these patients also exhibited leg-dominant symptoms and had tolerable or absent mechanical back pain. Administration of general anesthesia may be considerably hazardous in patients when combined with comorbid conditions that result from aging. Therefore, the present procedure was performed under local anesthesia. No obvious radiographic lumbar intervertebral instability was identified prior to surgery. Pre- and post-operative visual analogue scale (VAS) score, Oswestry Disability Index (ODI) and walking distance data were collected. The clinical global outcomes following surgery were evaluated using modified MacNab criteria. A total of 18 elderly patients underwent surgery using PTED techniques. The mean follow-up time was 27.7 months (range, 24-33 months) and the mean estimated blood loss was 18.33 ml (range, 10-35 ml). The mean pre-operative ODI, VAS score of the back and VAS score of the leg were 68.2±6.5, 2.8±1.4 and 6.6±1.2, respectively. All average scores improved post-operatively to 31.7±5.2, 1.5±0.6 and 1.7±0.8, respectively, at the latest follow-up. A statistically significant improvement was observed for all scores at 1 month and that the scores remained relatively stable after that. According to modified MacNab criteria, the good-to-excellent rate was 83.3%. Only 1 patient required micro-decompression surgery due to poor rating. The present study indicated that PTED may be an effective alternative therapeutic option for elderly patients with low-grade DLS associated with spinal stenosis. However, PTED techniques continue to evolve and further follow-up studies are required to determine the long-term outcomes of this treatment technique.

16.
Proc (Bayl Univ Med Cent) ; 34(1): 153-155, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-33456183

RESUMO

Histiocytic glomerulopathy, an entity characterized by glomerular infiltration by foamy histiocytes with endothelial injury, has recently been reported as a manifestation of hemophagocytic syndrome. We report a case of histiocytic glomerulopathy in a woman receiving chemotherapy for ovarian serous carcinoma with proteinuria in whom hemophagocytic syndrome was not clinically suspected.

17.
Br J Cancer ; 121(1): 37-50, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31133691

RESUMO

BACKGROUND: Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFR-targeted therapies. METHODS: To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRASG13D allele (mtKRAS). RESULTS: RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGFα stimulation, which was associated with an unexpected downregulation of genes involved in a range of anabolic processes. While TGFα treatment strongly activated protein synthesis in wtKRAS cells, protein synthesis was not activated above basal levels in the TGFα-treated mtKRAS cells. This was likely due to the defective activation of the mTORC1 and other pathways by TGFα in mtKRAS cells, which was associated with impaired activation of PKB signalling and a transient induction of AMPK signalling. CONCLUSIONS: We have found that mtKRAS cells are substantially rewired at the transcriptional, translational and metabolic levels and that this rewiring may reveal new vulnerabilities in oncogenic KRAS CRC cells that could be exploited in future.


Assuntos
Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Transcrição Gênica , Proteínas Quinases Ativadas por AMP/fisiologia , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Receptores ErbB/fisiologia , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/fisiologia , Metabolômica , Ribossomos/fisiologia , Transdução de Sinais , Fator de Crescimento Transformador alfa/farmacologia
18.
World Neurosurg ; 126: e517-e525, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30825627

RESUMO

BACKGROUND: Decompression alone is a treatment option in patients with lumbar spinal stenosis (LSS) and degenerative lumbar spondylolisthesis (DLS). This study aims to describe the procedure of percutaneous transforaminal endoscopic ventral decompression technique and to demonstrate the clinical outcomes. METHODS: Two years of retrospective data were collected from 26 patients with predominant unilateral leg pain caused by LSS and low-grade DLS (Meyerding grades I and Ⅱ). All patients underwent endoscopic ventral decompression by removing the posterosuperior margin underneath the slipping vertebral body, combined with dorsal decompression without excessive resection of facet joints. The surgical outcomes were assessed using the visual analog scale (VAS), Oswestry Disability Index (ODI), modified MacNab criteria, and walking distance improvement evaluation. RESULTS: The mean age of the 18 women and 8 men was 69.2 years. The mean preoperative ODI and VAS of the leg and the back scores were 64.7 ± 8.1, 7.0 ± 1.4, and 3.0 ± 1.2, respectively. All mean scores improved postoperatively to 31.4 ± 5.6, 2.4 ± 1.1, and 1.7 ± 1.1 at the final follow-up. In 88.5% of cases, patients' estimated walking distance improved. The outcomes of the modified MacNab criteria showed that 81.3% of patients obtained good-to-excellent rate. There were no statistically significant differences between the percent slip of spondylolisthesis before surgery and at the end of follow-up. CONCLUSIONS: Based on the initial short-term follow-up results, transforaminal endoscopic ventral decompression by partially removing the posterosuperior margin underneath the slipping vertebral body, combined with dorsal decompression, might be an efficient alternative treatment for leg dominant symptoms in patients with LSS and low-grade DLS.


Assuntos
Descompressão Cirúrgica/métodos , Endoscopia/métodos , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Idoso , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
World Neurosurg ; 123: 283-285, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30580065

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease caused by mutation on chromosome 17, which affects the skin, vascular system, nervous system, and skeleton system. Arteriovenous fistula (AVF) is one of the recognized complications of NF-1. CASE DESCRIPTION: We report a case of a 33-year-old woman with NF-1 with cervical spine AVF inside the cervical spinal canal who presented with progressive spinal cord compression which was abnormal. After sufficient preparation, the patient underwent vascular embolization, and then symptoms of spinal cord compression significantly improved. CONCLUSIONS: This report reminds readers of the possibility of AVF if there is a space-occupying lesion inside the cervical spinal canal and to do computed tomography angiography examination when necessary.


Assuntos
Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/patologia , Neurofibromatose 1/complicações , Canal Medular/patologia , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/cirurgia , Angiografia por Tomografia Computadorizada , Embolização Terapêutica/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/cirurgia , Canal Medular/diagnóstico por imagem , Canal Medular/cirurgia
20.
Analyst ; 144(1): 157-160, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30516177

RESUMO

Ordered PdCu and Co doped PdCu nanoparticles have been synthesized on graphene oxide (GO). The obtained Co-PdCu/GO composites were used to fabricate a H2O2 electrochemical sensor which exhibits an ultralow LOD (limit of detection) of 1.2 nM and an extra broad linear range of 5 nM-5.774 mM, and has been used to detect H2O2 in living cells successfully.


Assuntos
Cobalto/química , Cobre/química , Grafite/química , Peróxido de Hidrogênio/análise , Nanopartículas Metálicas/química , Paládio/química , Animais , Linhagem Celular Tumoral , Técnicas Eletroquímicas/métodos , Limite de Detecção , Óxidos/química , Tamanho da Partícula , Ratos
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