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1.
Proc Natl Acad Sci U S A ; 119(46): e2212406119, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346846

RESUMO

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.


Assuntos
Anuros , Raios Ultravioleta , Animais , Anuros/genética , Pele , Perfilação da Expressão Gênica , Antioxidantes
2.
Int Orthop ; 48(6): 1489-1499, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38443716

RESUMO

PURPOSE: To compare the outcomes of type II pediatric phalangeal neck fractures (PPNFs) treated with closed reduction and cast immobilization (CRCI) versus closed reduction percutaneous pinning (CRPP), and evaluated the clinical efficacy of conservative versus surgical treatment of type II PPNFs via meta-analysis. METHODS: Patients aged ≤ 14 years with type II PPNFs were divided into conservative (CRCI) and operative (CRPP) groups. Radiographs measured angulation and translation; hand function was assessed with total active range of motion (TAM) and Quick-DASH. Complication rates were also compared between the groups. A meta-analysis of conservative versus operative treatment confirmed the clinical results. Statistical analysis was performed using SPSS 26.0 and R studio 3.0 with two-tailed, chi-squared, and Mann-Whitney U or t-tests, P < 0.05. Meta-analysis used fixed or random effects models, calculating mean differences and odds ratios for outcomes, and assessing heterogeneity with I2 and Q tests. RESULTS: Final angulation (3.4° ± 3.7° and 4.9° ± 5.4° vs. 3.6° ± 3.7° and 4.2° ± 4.3°) and displacement (6.3% ± 5.8% and 5.7% ± 4.7% vs. 5.8% ± 5.5% and 3.2% ± 4.2%) in the coronal and sagittal planes were not different statistically between the conservative and surgical groups (P > 0.05), but improved significantly compared to preoperative values (P < 0.05). Although Quick-DASH scores were comparable in both groups (P = 0.105), conservatively treated patients had a significantly better TAM at the last follow-up visit (P = 0.005). The complication rates were 24.2% and 41.7% in the surgical and conservatively treated groups respectively (P = 0.162). However, the latter primarily experienced imaging-related complications, whereas the former experienced functional complications (P = 0.046). Our meta-analysis (n = 181 patients) also showed comparable functional (P = 0.49) and radiographic (P = 0.59) outcomes and complication rates (P = 0.21) between the surgical (94 patients) and conservative (87 patients) groups. CONCLUSIONS: Conservative and surgical treatments are both reliable and safe approaches for managing type II PPNF in children. However, conservatively treated patients generally experience similar radiographic outcomes, lower complication rates, and better functional outcomes than surgically treated ones.


Assuntos
Fios Ortopédicos , Moldes Cirúrgicos , Falanges dos Dedos da Mão , Humanos , Criança , Falanges dos Dedos da Mão/lesões , Falanges dos Dedos da Mão/cirurgia , Masculino , Feminino , Adolescente , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/efeitos adversos , Resultado do Tratamento , Fraturas Ósseas/cirurgia , Amplitude de Movimento Articular , Pré-Escolar
3.
Kidney Int ; 103(5): 903-916, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36805450

RESUMO

Accumulating evidence highlights mitochondrial dysfunction as a crucial factor in the pathogenesis of acute kidney injury (AKI); thus, novel therapeutic strategies maintaining mitochondrial homeostasis are highly anticipated. Recent studies have shown that cobaltosic oxide has peroxidase-like catalytic activities, although its role and mechanism remain elusive in AKI. In the present study, we synthesized and identified cobaltosic oxide-polyethylene glycol-triphenylphosphine (COPT) nanoparticles by conjugating cobaltosic oxide with polyethylene glycol and triphenylphosphine, to improve its biocompatibility and mitochondria-targeting property. We found that COPT preferentially accumulated in the kidney proximal tubule cells, and significantly alleviated ischemic AKI in mouse models and gentamicin induced-AKI in the zebrafish model. COPT also inhibited the transition from AKI to chronic kidney disease (CKD), with few side effects. Further studies demonstrated that COPT localized in the mitochondria, and ameliorated hypoxia-reoxygenation-mediated mitochondrial damage through enhancing mitophagy in vitro and in vivo. Mechanistically, COPT dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 attenuated COPT-induced mitophagic flux and mitochondrial protection. Thus, our findings suggest that COPT nanoparticles ameliorate AKI and its progression to CKD through inducing BNIP3-mediated mitophagy, indicating that COPT may serve as a promising mitochondria-targeting therapeutic agent against AKI.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Camundongos , Animais , Mitofagia , Peixe-Zebra/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Injúria Renal Aguda/patologia , Proteínas Mitocondriais/metabolismo , Proteínas de Membrana/metabolismo
4.
J Environ Manage ; 337: 117679, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36934504

RESUMO

Coal tar residue (CTR) is acknowledged as hazardous industrial waste with high contents of carbon and toxic polycyclic aromatic hydrocarbons (PAHs). Microwave-assisted extraction for separating tar and residue in CTR was investigated to reduce the content of PAHs. The key operating factors such as solvent type, solvent addition amount, radiation temperature, and radiation time in the extraction process were evaluated. Results showed that extreme extraction performance in the solvent with cyclic structure was attained, and an enhancement in extraction efficiency was achieved in elevated solvent addition amount, radiation temperature, or radiation time in a certain range. The optimized conditions were determined as benzene was chosen as extractant, solvent-solid ratio of 5:1 mL/g, radiation temperature of 75 °C, and radiation time of 10 min. Relative extraction efficiency of CTR and reduction efficiency of 16 priority control PAHs were 28.70% and 92.82%, respectively. According to the characterizations of extracted residue (MCTR) and tar (MCT) under optimum experimental conditions, it is possible to convert them into value-added products (carbon materials, solid fuels, or chemicals). Solid-oil separation via microwave-assisted extraction is a safe and high-valued utilization approach for CTR.


Assuntos
Alcatrão , Hidrocarbonetos Policíclicos Aromáticos , Alcatrão/química , Hidrocarbonetos Policíclicos Aromáticos/química , Micro-Ondas , Solventes , Carbono
5.
Anal Chem ; 94(10): 4243-4251, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35235297

RESUMO

The discrimination between dead and live cells is crucial for cell viability evaluation. Carbon dots (CDs), with advantages like simple and cost-effective synthesis, excellent biocompatibility, and high photostability, have shown potential for realizing selective live/dead cell staining. However, most of the developed CDs with the live/dead cell discrimination capacity usually have low photoluminescence quantum yields (PLQYs) and excitation wavelength-dependent fluorescence emission (which can cause fluorescence overlap with other fluorescent probes and make dual-color live/dead staining impossible), and hence, developing ultrabright CDs with excitation wavelength-independent fluorescence emission property for live/dead cell discrimination becomes an important task. Here, using a one-pot hydrothermal method, we prepared ultrasmall (∼1.6 nm), ultrabright (PLQY: ∼78%), and excitation wavelength-independent sulfur-doped carbon dots (termed S-CDs) using rose bengal and 1,4-dimercaptobenzene as raw materials and demonstrated that the S-CDs could rapidly (∼5 min) and accurately distinguish dead cells from live ones for almost all the cell types including bacterial, fungal, and animal cells in a wash-free manner. We confirmed that the S-CDs could rapidly pass through the dead cell surfaces to enter the interior of the dead cells, thus visualizing these dead cells. In contrast, the S-CDs could not enter the interior of live cells and thus could not stain these live cells. We further verified that the S-CDs presented better biocompatibility and higher photostability than the commercial live/dead staining dye propidium iodide, ensuring its bright application prospect in cell imaging and cell viability assessment. Overall, this work develops a type of CDs capable of realizing the live/dead cell discrimination of almost all the cell types (bacterial, fungal, and animal cells), which has seldom been achieved by other fluorescent nanoprobes.


Assuntos
Carbono , Pontos Quânticos , Animais , Corantes Fluorescentes , Nitrogênio , Pontos Quânticos/toxicidade , Rosa Bengala , Enxofre
6.
Anticancer Drugs ; 33(10): 1156-1162, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946545

RESUMO

Bladder cancer is the most common malignancy in the urinary system, and muscle-invasive bladder cancer (MIBC) accounts for 25-30% among all types of bladder cancers. Although MIBC can be treated by surgery and chemotherapy, favorable outcomes can still not be obtained. In recent years, the emergence of immunotherapy represented by programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors and other immune checkpoint inhibitors provides attractive prospects for the treatment of advanced bladder cancer. PD-1/PD-L1 inhibitors can block the binding of PD-1/PD-L1, which can block negative immunomodulatory signals, thereby improving anti-tumor immune activity. In this article, we reported a case of advanced MIBC who achieved complete pathological remission after receiving the combined therapy of toripalimab and chemotherapy, which could provide clinical data for the treatment of bladder cancer with triprizumab.


Assuntos
Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Humanos , Inibidores de Checkpoint Imunológico , Músculos/metabolismo , Músculos/patologia , Receptor de Morte Celular Programada 1 , Neoplasias da Bexiga Urinária/patologia
7.
Proc Natl Acad Sci U S A ; 116(44): 22347-22352, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31611410

RESUMO

Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.


Assuntos
Bainha de Mielina/ultraestrutura , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/metabolismo , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Bainha de Mielina/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Ratos
8.
BMC Surg ; 22(1): 169, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538469

RESUMO

BACKGROUND: Intussusception recurrence (IR) induced by intestinal lymphoid hyperplasia (ILH) in children is rare, and surgical treatment is the final resort if IR is refractory to medications and non-surgical interventions. To date, only a few case reports have described surgical management of ILH-induced IR in children, all involving bowel resection regardless of whether there are bowel necrosis and perforation. CASE PRESENTATION: A 2-year-old boy was transferred to our department due to IR. His main complaint was abdominal pain. Color Doppler ultrasound confirmed ileocecal intussusception while no other abnormalities were found. A final diagnosis of IR with unknown causes was made. Repeated saline enema reductions and dexamethasone failed to cure the IR. Laparotomy was eventually performed after almost 10 episodes of IR. Intraoperatively, distal ileum thickening with palpable masses without bowel necrosis and perforation was noted. ILH was suspected and a biopsy of the affected intestine was performed. Histopathological analysis confirmed ILH. The intussusception was manually reduced, the terminal ileum and the ileocecal junction were fixed to the paralleled ascending colon and the posterior peritoneum respectively, and no bowel resection was performed. The postoperative recovery was uneventful and no IR was observed during over 5 years of follow-up. CONCLUSIONS: As far as we are aware, this is the first report of successful surgical treatment of ILH-induced pediatric IR without bowel resection in a child. Our experience suggests bowel resection may be unnecessary if bowel necrosis and perforation are absent.


Assuntos
Enteropatias , Intussuscepção , Criança , Pré-Escolar , Enema/efeitos adversos , Humanos , Hiperplasia/complicações , Hiperplasia/patologia , Íleo/patologia , Íleo/cirurgia , Enteropatias/patologia , Intussuscepção/etiologia , Intussuscepção/cirurgia , Masculino , Necrose/patologia
9.
COPD ; 19(1): 61-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35099333

RESUMO

Racial and ethnic disparities in chronic obstructive pulmonary disease (COPD) are not well-studied. Our objective was to examine differences in limited COPD-related outcomes between three minority groups-African Americans (AAs), Hispanics, and American Indians (AIs) versus non-Hispanic Whites (NHWs), as the referent group, in separate cohorts. Separate cross-sectional evaluations were performed of three US-based cohorts of subjects at risk for COPD: COPDGene Study with 6,884 NHW and 3,416 AA smokers; Lovelace Smokers' Cohort with 1,598 NHW and 378 Hispanic smokers; and Mining Dust Exposure in the United States Cohort with 2,115 NHW, 2,682 Hispanic, and 2,467 AI miners. Prebronchodilator spirometry tests were performed at baseline visits using standard criteria. The primary outcome was the prevalence of airflow obstruction. Secondary outcomes were self-reported physician diagnosis of COPD, chronic bronchitis, and modified Medical Research Council dyspnea score. All minority groups had a lower prevalence of airflow obstruction than NHWs (adjusted ORs varied from 0.29 in AIs to 0.85 in AAs; p < 0.01 for all analyses). AAs had a lower prevalence of chronic bronchitis than NHWs. In our study, all minority groups had a lower prevalence of airflow obstruction but a greater level of self-reported dyspnea than NHWs, and covariates did not explain this association. A better understanding of racial and ethnic differences in smoking-related and occupational airflow obstruction may improve prevention and therapeutic strategies.


Assuntos
Bronquite Crônica , Doença Pulmonar Obstrutiva Crônica , Estudos Transversais , Dispneia , Minorias Étnicas e Raciais , Humanos , Prevalência , Estados Unidos/epidemiologia
10.
Arch Orthop Trauma Surg ; 142(6): 913-926, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33417022

RESUMO

BACKGROUND: Perioperative pain after total knee arthroplasty (TKA) may seriously affect the rapid recovery of patients. The purpose of this study was to assess whether the combined use of adductor canal block (ACB) and local infiltration anesthesia (LIA) can further reduce postoperative pain and improve early functional recovery. MATERIALS AND METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing ACB + LIA and LIA alone in primary TKA. The primary outcomes were visual analog scale (VAS) scores at rest and walking, morphine consumption, range of motion (ROM) at 24 and 48 h postoperatively and distance walked. The secondary outcomes were the length of stay, the incidence of nausea and vomiting, and the total complications. Subgroup analyses were performed on the VAS at rest and walking, morphine consumption, and distance walked at 24, 48, and 72 h postoperatively. RESULTS: A total of 10 RCTs involving 797 patients were enrolled in this meta-analysis. The results demonstrated that the combined application of ACB + LIA had a lower resting VAS at 24 h postoperatively (p = 0.02) and the walking score at 24 (p = 0.0002) and 48 h (p = 0.02) postoperatively compared with LIA alone. Similarly, the combined ACB + LIA group also had less morphine consumption at 48 h postoperatively (p = 0.0005) and had a higher ROM score at 24 h (p = 0.01) postoperatively compared to the LIA group. There were no statistical differences in length of stay, distance walked, and incidence of nausea and vomiting. CONCLUSION: The current meta-analysis showed that ACB + LIA significantly reduced postoperative walking pain and morphine consumption and promoted rapid recovery in the early postoperative period. There is no statistical difference in the length of stay and ROM after 72 h in the two groups.


Assuntos
Artroplastia do Joelho , Bloqueio Nervoso , Analgésicos Opioides , Anestesia Local , Anestésicos Locais , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Humanos , Morfina/uso terapêutico , Náusea/complicações , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/complicações
11.
Biomacromolecules ; 22(8): 3590-3600, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34286578

RESUMO

One of the biggest challenges of the protein delivery system is to realize stable and high protein encapsulation efficiency in blood circulation and rapid release of protein in the targeted tumor cells. To overcome these hurdles, we fabricated enzyme-responsive photo-cross-linked nanogels (EPNGs) through UV-triggered chemical cross-linking of cinnamyloxy groups in the side chain of PEGylation hyaluronic acid (HA) for CD44-targeted transport of cytochrome c (CC). The EPNGs showed high loading efficiency and excellent stability in different biological media. Notably, CC leakage effectively suppressed under physiological conditions but accelerated release in the presence of hyaluronidase, an overexpressed enzyme in tumor cells. Moreover, thiazolylblue tetrazolium bromide (MTT) results indicated that the vacant EPNGs showed excellent nontoxicity, while CC-loaded EPNGs exhibited higher killing efficiency to CD44-positive A549 cells than to CD44-negative HepG2 cells and free CC. Confocal images confirmed that CC-loaded EPNGs could effectively be internalized by CD44-mediated endocytosis pathway and rapidly escape from the endo/lysosomal compartment. Human lung tumor-bearing mice imaging assays further revealed that CC-loaded EPNGs actively target tumor locations. Remarkably, CC-loaded EPNGs also exhibited enhanced antitumor activity with negligible systemic toxicity. These results implied that these EPNGs have appeared as stable and promising nanocarriers for tumor-targeting protein delivery.


Assuntos
Nanopartículas , Células A549 , Animais , Linhagem Celular Tumoral , Humanos , Ácido Hialurônico , Camundongos , Nanogéis
12.
J Dairy Sci ; 104(1): 151-166, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33162079

RESUMO

Koumiss is a type of famous fermented mare milk and considered an important nutritious beverage in central Asian countries. However, the production of koumiss cannot meet public demand in the market due to availability of mare milk. In the present study, 52 lactic acid bacteria and 20 yeast strains from traditional homemade Kazakhstan koumiss were isolated and identified. The isolates were used in a trial that included fermented cow milk, and the flavor profiles, color, and taste to determine their contribution in the co-fermentation of cow milk. Based on the sensory evaluation, KZLAB13 and KZY10 strains were selected as the best cofermentation combinations. The optimal fermentation conditions were confirmed as the ratio of the starter culture 2.4:1.6 % (vol/vol) KZLAB13 strain to KZY10 strain and a temperature of 36°C for 16 h using response surface methodology. After evaluating the quality of the optimized cow-milk koumiss compared with the Kazakhstan koumiss, results suggested that cow milk fermented by these 2 strains possessed a promising taste, flavor, and physicochemical and rheological properties. Altogether, our results showed that cow milk fermented with a combination of KZLAB13 and KZY10 strains can simulate the taste, flavor, and quality of traditional koumiss. Our study provided a novel alternative to mare-milk koumiss and could be used in dairy programs to fulfill the needs of people.


Assuntos
Kumis/microbiologia , Lactobacillales/metabolismo , Leite/microbiologia , Animais , Bovinos , Feminino , Fermentação , Cavalos , Cazaquistão , Lactobacillales/isolamento & purificação , Leite/metabolismo , Paladar , Leveduras/isolamento & purificação
13.
Ren Fail ; 43(1): 1137-1145, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34261422

RESUMO

BACKGROUND AND AIMS: Early detection of acute kidney injury (AKI) is crucial for the prognosis of patients after liver transplantation (LT). This passage aims to analyze the perioperative clinical markers of AKI after LT and establish predictive models based on clinical variables for early detection of AKI after LT. METHODS: We prospectively collected 109 patients with LT, and compared the differences of perioperative clinical markers between the AKI group and non-AKI group. The scoring system and decision tree model were established through the risk factors. Another 163 patients who underwent LT in the same center from 2017 to 2018 were retrospectively collected to verify the models. RESULTS: In multiple comparisons of risk factors of post-LT AKI, pre-operative factors were excluded automatically, intraoperative and post-operative factors including operating time, intraoperative hypotension time, post-operative infection, the peak of post-operative AST, and post-operative shock were the independent risk factors for post-LT AKI. The scoring system established with the risk factors has good predictive power (AUC = 0.755) in the validation cohort. The decision tree also shows that post-operative shock was the most important marker, followed by post-operative infection. CONCLUSION: Five intraoperative and post-operative factors are independently associated with post-LT AKI rather than pre-operative factors, which indicates that operation technique and post-operative management may more important for the prevention of post-LT AKI. The scoring system and decision tree model could complement each other, and provide quantitative and intuitive prediction tools for clinical practice of early detection of post-LT AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Árvores de Decisões , Transplante de Fígado/efeitos adversos , Adulto , Feminino , Humanos , Hipotensão/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
14.
J Cell Mol Med ; 24(22): 12994-13009, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969198

RESUMO

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Túbulos Renais Proximais/metabolismo , RNA Longo não Codificante , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proliferação de Células , Nefropatias Diabéticas/metabolismo , Receptores ErbB/metabolismo , Glucose , Humanos , Hibridização in Situ Fluorescente , Túbulos Renais Proximais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Oligonucleotídeos Antissenso/farmacologia , Ligação Proteica , RNA Longo não Codificante/genética , RNA-Seq , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitina/metabolismo
15.
Neurobiol Learn Mem ; 175: 107310, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890758

RESUMO

Risk perception is an important factor that may mediate risk-based decision-making processes regulated by noradrenergic (NA) and serotonergic (5-HT) systems. Most risk-based decision-making models involve complex factors, such as risk perception or reward value, such that the final decision is the result of the interactions among these factors. However, the contribution of risk perception per se in risk decisions has remained unclear. Therefore, in the present study, we made some modifications to the classical probabilistic discounting task (PDT) to focus on the impact of risk perception and noradrenergic/serotonergic systems on decision-making behavior. Meanwhile, we conducted an elevated plus-maze (EPM) test to detect the correlation between anxiety and choice behavior. In the current study, rats had to choose between a "certain" lever that delivered a certain number of pellets and a "risky" lever that delivered eight pellets in a probabilistic manner (descending: 50%, 25%, 12.5% or ascending 12.5%, 25%, 50% of the time). The long-term rewarding values of the two levers were always identical in each block within each session. According to their baseline performances in choosing the risky lever, rats were divided into the risk-prefer group and risk-averse group. The results showed that there was a significant correlation between open arm time in EPM and risky choice for both descending order and ascending order, indicating that highly anxious rats more often preferred the safe option under risk. Pharmacological stimulation of α2-adrenergic receptors via dexmedetomidine (0.01 mg/kg) decreased the preference of probabilistic rewards in the risk-prefer group, while blocking α2 receptors by atipamezole (0.3 mg/kg) also reduced risky choices. The NA reuptake inhibitor, atomoxetine, increased the preference for risky choices in the risk-prefer group, the effect of which was attained via multiple superimposed doses. Administration of the 5-HT2A receptor agonist, DOI (0.1 mg/kg), increased risk-taking behavior in the risk-prefer group. Taken together, these results suggest that NA may be more inclined to process negative information such as loss or uncertainty in the regulation of risk-related decision making, whereas 5-HT may function primarily to increase risk-taking behavior. Our findings may help to further elucidate how noradrenergic and serotonergic systems differentially affect individuals with different risk preferences in terms of regulating risk perception in risk-related decision making.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Tomada de Decisões/efeitos dos fármacos , Recompensa , Assunção de Riscos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Anfetaminas/farmacologia , Animais , Tomada de Decisões/fisiologia , Dexmedetomidina/farmacologia , Imidazóis/farmacologia , Ratos , Medição de Risco
16.
Small ; 15(33): e1900501, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31282114

RESUMO

Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin-based tumor microenvironment-responsive nanoagent is designed via the self-assembly of human serum albumin (HSA), dc-IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting-mediated mild-temperature PTT. The formed HSA/dc-IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near-infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia-induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc-IR825/GA NPs show pH-responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild-temperature PTT and chemotherapy. Taken together, the NIR-activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild-temperature PTT-based combination strategies.


Assuntos
Albuminas/administração & dosagem , Hipertermia Induzida/métodos , Terapia de Alvo Molecular , Fototerapia/métodos , Células A549 , Albuminas/farmacocinética , Animais , Terapia Combinada , Endocitose , Humanos , Camundongos , Nanopartículas/uso terapêutico , Neoplasias/terapia , Temperatura , Distribuição Tecidual
17.
Langmuir ; 35(18): 6039-6047, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983367

RESUMO

Sewage sludge-derived mesoporous biochars (SS-MBCs) were prepared by using cationic polyacrylamide (PAM+) as a template agent through a template-like method under high temperature and employed for getting rid of methylene blue (MB) from water. Textural evolution, mesostructured morphology, thermodynamic properties, and surface chemical groups of SS-MBCs were analyzed. It showed that PAM+ not only played an important role in good nucleation that brought well-developed texture and novel pore size distribution to SS-MBCs but also improved the MB adsorption capacities of SS-MBCs by increasing the specific surface area and the content of oxygen functional groups, especially the lactone. Preparation factor analysis indicated that PAM+ concentration, dosage of additive sludge, and carbonization temperature had distinct effects on material structure and adsorption performance especially above the pyrolytic temperature of 800 °C. The adsorption kinetics and isotherms were analyzed in detail, and it revealed that the kinetics and equilibrium adsorptions of SS-MBCs could be well-described by the Langmuir isotherm model and pseudo-second-order kinetics, respectively. Remarkably, the SS-MBCs showed higher removal efficiency and adsorption capacity than commercial activated carbon and most reported sludge-based adsorbents.

18.
Surg Endosc ; 33(4): 1033-1048, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30719561

RESUMO

BACKGROUND: To evaluate short- and long-term outcomes of robotic gastrectomy (RG) in patients with gastric cancer to determine whether RG is an acceptable alternative to laparoscopic gastrectomy (LG). METHODS: PubMed, Embase, the Cochrane Library, and Chinese Biomedical Database were searched for prospective observational studies (POSs) comparing RG with LG for gastric cancer until October 2017. We compared short-term and long-term outcomes using systematic review with meta-analysis and trial sequential analysis (TSA). RESULTS: Sixteen POSs including 4576 patients were included in the meta-analyses. Compared with LG, RG had longer operative time (MD 57.98 min, P < 0.00001), lesser blood loss (MD - 23.71 ml, P = 0.005), and shorter time to first post-operative flatulence (MD - 0.14 days, P = 0.03). No significant difference was found in terms of the number of harvested lymph nodes, complications, reoperation, mortality, open conversion, proximal resection margin, and distal resection margin. The meta-analyses of complications, overall survival, and disease-free survival did not yield any sign of statistically significant difference between the two treatments, and the cumulative Z-curve crossed neither the traditional boundary nor the trial sequential monitoring boundary, suggesting the lack of firm evidence. TSA demonstrated that the cumulative Z-curve crossed either the traditional boundary or the trial sequential monitoring boundary on blood loss and operative time. CONCLUSIONS: The present study demonstrates that RG is as acceptable as LG in terms of short- and long-term outcomes. The TSA demonstrated that further studies are not needed to evaluate the operative time and blood loss differences between these techniques.


Assuntos
Gastrectomia/métodos , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas/cirurgia , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Laparoscopia/efeitos adversos , Masculino , Estudos Observacionais como Assunto , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Reoperação , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
19.
Acta Radiol ; 60(6): 762-768, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30249113

RESUMO

BACKGROUND: Calcium (water) density (DCa(Wa)) of gemstone spectral imaging by spectral computed tomography (CT) is a new method of evaluating bone structures. PURPOSE: To investigate age-related change of DCa(Wa) of a chosen lumbar vertebra in adult women with spectral CT and the correlation between the DCa(Wa) and bone mineral density (BMD) of dual-energy X-ray absorptiometry (DXA). MATERIAL AND METHODS: A total of 305 adult women underwent spectral CT, 127 of whom simultaneously underwent DXA. All the patients were divided into 11 subgroups based on age. DCa(Wa) and BMD were measured at the second lumbar vertebra on the calcium (water)-based material decomposition images of spectral CT and DXA, respectively. A one-way analysis of variance (ANOVA) was performed for the difference of the measurements among adjacent age subgroups. Pearson correlation was used to assess the association between age and DCa(Wa), age and BMD, as well as DCa(Wa) and BMD. RESULTS: There was a significant negative correlation between DCa(Wa) and age (r = -0.719) as well as BMD and age(r = -0.851). The mean DCa(Wa) of L2 vertebral body was significantly different between the 40-44- and 45-49-, 45-49- and 50-54-, 55-59- and 60-64-, 65-69- and 70-74-year-old age subgroups. BMD was significantly different between the 35-39- and 40-44-, 45-49- and 50-54-, and 65-69- and 70-74-year-old age subgroups. There was a significant positive correlation between DCa(Wa) and BMD. CONCLUSIONS: The DCa(Wa) of lumbar vertebra by spectral CT demonstrated similar age distribution as BMD of DXA and could be used as a method of measuring the vertebral bone mineral density in adult women.


Assuntos
Densidade Óssea , Cálcio/metabolismo , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Absorciometria de Fóton , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Análise de Variância , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoporose/metabolismo , Reprodutibilidade dos Testes
20.
Acta Radiol ; 59(7): 853-860, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28899125

RESUMO

Background The evaluation of hip arthroplasty is a challenge in computed tomography (CT). The virtual monochromatic spectral (VMS) images with metal artifact reduction software (MARs) in spectral CT can reduce the artifacts and improve the image quality. Purpose To evaluate the effects of VMS images and MARs for metal artifact reduction in patients with unilateral hip arthroplasty. Material and Methods Thirty-five patients underwent dual-energy CT. Four sets of VMS images without MARs and four sets of VMS images with MARs were obtained. Artifact index (AI), CT number, and SD value were assessed at the periprosthetic region and the pelvic organs. The scores of two observers for different images and the inter-observer agreement were evaluated. Results The AIs in 120 and 140 keV images were significantly lower than those in 80 and 100 keV images. The AIs of the periprosthetic region in VMS images with MARs were significantly lower than those in VMS images without MARs, while the AIs of pelvic organs were not significantly different. VMS images with MARs improved the accuracy of CT numbers for the periprosthetic region. The inter-observer agreements were good for all the images. VMS images with MARs at 120 and 140 keV had higher subjective scores and could improve the image quality, leading to reliable diagnosis of prosthesis-related problems. Conclusion VMS images with MARs at 120 and 140 keV could significantly reduce the artifacts from hip arthroplasty and improve the image quality at the periprosthetic region but had no obvious advantage for pelvic organs.


Assuntos
Artroplastia de Quadril/instrumentação , Artefatos , Articulação do Quadril/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Metais , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos
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