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1.
Sci Total Environ ; 933: 172935, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38703859

RESUMO

The deleterious impact of pollution point sources on the surrounding environment and human has long been a focal point of environmental research. When considering the local atmospheric dispersion of semi-volatile organic compounds (SVOCs) around the emission sites, it is essential to account the dynamic process for the gas/particle (G/P) partitioning, which involves the transition from an initial state to a steady state. In this study, we have developed a model that enables the prediction of the dynamic process for G/P partitioning of SVOCs, particularly considering the influence from emission. It is important to note that the dynamic processes of the concentrations of SVOCs in particle phase (CP) and in gas phase (CG) differ significantly. These differences arise due to the influence of two critical factors: particulate proportion of SVOCs in the emissions (ϕ0) and octanol-air partitioning coefficient (KOA). The validity of our model was assessed by comparing its predictions of the extremum value of the G/P partitioning quotient (KP) with the results obtained from the steady-state model. Remarkably, the characteristic time (tC), used to evaluate the timescale required for SVOCs to reach steady state, demonstrated different variations with KOA for CP and CG. Additionally, the values of tC were quite different for CP and CG, which were markedly influenced by ϕ0. For some SVOCs with high KOA values, it took approximately 35 h to reach steady state. Furthermore, it was found that the time to achieve 95 % of steady state (t95 ≈ 3tC) could reach approximately 105 h. This duration is sufficient for chemicals to disperse from their emission site to the surrounding areas. Therefore, it is crucial to consider the dynamic process of G/P partitioning in local atmospheric transport studies. Moreover, the influence of ϕ0 should be incorporated into future investigations examining the dynamic process of G/P partitioning.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38412702

RESUMO

This study compares the skin structures of Rana kukunoris with two different skin colors living in the same area of Haibei in the Northeastern Qinghai-Tibet Plateau. The skin thickness of the khaki R. kukunoris was significantly greater than that of the brown R. kukunoris (P < 0.01), and significantly more mucous and granular glands were present on the dorsal skin of the khaki frog (P < 0.05). Meanwhile, the melanocytes on the dorsal skin of the brown frog were significantly larger than those on the khaki one (P < 0.05). Morphological changes in the expansion and aggregation of melanocytes seemed to deepen the skin color of R. kukunoris. Moreover, transcriptome sequencing identified tyrosine metabolism, melanogenesis, and riboflavin metabolism as the main pathways involved in melanin formation and metabolism in brown R. kukunoris. TYR, MC1R was upregulated as the skin color of R. kukunoris was deepened and contributed to melanin production and metabolism. In contrast, the khaki frog had significantly more upregulated genes and metabolic pathways related to autoimmunity. The khaki frog appeared to defend against ultraviolet (UV) radiation-induced damage by secreting mucus and small molecular peptides, whereas the brown frog protected itself by distributing a large amount of melanin. Hence, the different skin colors of R. kukunoris might represent different adaptation strategies for survival in the intense UV radiation environment of the Qinghai-Tibet Plateau.


Assuntos
Ranidae , Pigmentação da Pele , Pele , Transcriptoma , Animais , Ranidae/genética , Pigmentação da Pele/genética , Pele/metabolismo , Perfilação da Expressão Gênica , Melaninas/metabolismo
4.
Biomed Pharmacother ; 165: 115019, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37329709

RESUMO

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inflamassomos/metabolismo , Proteínas NLR
5.
World J Clin Cases ; 11(7): 1576-1585, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36926402

RESUMO

BACKGROUND: Intracranial hemorrhage is extremely rare during the initial stages of glioma. Here, we report a case of glioma with unclassified pathology and intracranial bleeding. CASE SUMMARY: After the second surgery for intracerebral hemorrhage, the patient experienced weakness in the left arm and leg, but could walk unassisted. One month after discharge, the weakness in the left limbs had exacerbated and the patient also suffered from headaches and dizziness. A third surgery was ineffective against the rapidly growing tumor. Intracerebral hemorrhage may be the initial symptom of glioma in some rare cases, and atypical perihematomal edema can be used for diagnosis during an emergency. Certain histological and molecular features seen in our case were similar to that of glioblastoma with a primitive neuronal component, which is termed diffuse glioneuronal tumor with features similar to oligodendroglioma and nuclear clusters (DGONC). The patient underwent three surgeries to remove the tumor. The first tumor resection had been performed when the patient was 14-years-old. Resection of the hemorrhage and bone disc decompression were performed when the patient was 39-years-old. One month after the last discharge, the patient underwent neuronavigation-assisted resection of the right frontotemporal parietal lesion plus extended flap decompression. On the 50th d after the third operation, computed tomography imaging showed rapid tumor growth accompanied by brain hernia. The patient was discharged and died 3 d later. CONCLUSION: Glioma can present as bleeding in the initial stage and should be considered in such a setting. We have reported a case of DGONC, which is a rare molecular subtype of glioma with a unique methylation profile.

6.
J Neurosurg ; 139(1): 20-28, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36681987

RESUMO

OBJECTIVE: The classic transopercular or transsylvian approach to insular gliomas removes the tumor laterally through the insular cortex. This study describes a new anteroposterior approach through the frontal isthmus for insular glioma surgery. METHODS: The authors detailed the surgical techniques for resection of insular gliomas through the transfrontal isthmus approach. Fifty-nine insular gliomas with at least Berger-Sanai zone I involvement were removed with the new approach, and extent of resection and postoperative neurological outcomes were assessed. RESULTS: Fifty-nine patients were enrolled in the study, including 35 men and 24 women, with a mean (range) age 44.3 (19-75) years. According to the Berger-Sanai classification system, the most common tumor was a giant glioma (67.8%), followed by involvement of zones I and IV (18.6%). Twenty-two cases were Yasargil type 3A/B, and 37 cases were Yasargil type 5A/B. The average angle between the lateral plane of the putamen and sagittal line was 33.53°, and the average width of the isthmus near the anterior insular point was 33.33 mm. The average angle between the lateral plane of the putamen and the sagittal line was positively correlated with the width of the isthmus near the anterior insular point (r = 0.935, p < 0.0001). The median (interquartile range [IQR]) preoperative tumor volume was 67.82 (57.64-92.19) cm3. Of 39 low-grade gliomas, 26 (66.67%) were totally resected; of 20 high-grade gliomas, 19 (95%) were totally resected. The median (IQR) extent of resection of the whole group was 100% (73.7%-100%). Intraoperative diffusion-weighted imaging showed no cases of middle cerebral artery- or lenticulostriate artery-related stroke. Extent of insular tumor resection was positively correlated with the angle of the lateral plane of the putamen and sagittal line (r = -0.329, p = 0.011) and the width of the isthmus near the anterior insular point (r = -0.267, p = 0.041). At 3 months postoperatively, muscle strength grade exceeded 4 in all cases, and all patients exhibited essentially normal speech. The median (IQR) Karnofsky performance score at 3 months after surgery was 90 (80-90). CONCLUSIONS: The transfrontal isthmus approach changes the working angle from lateral-medial to anterior-posterior, allowing for maximal safe removal of insular gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Masculino , Humanos , Feminino , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Resultado do Tratamento , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/cirurgia , Córtex Cerebral/patologia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Procedimentos Neurocirúrgicos/métodos , Artéria Cerebral Média
7.
Biomed Pharmacother ; 148: 112785, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35272138

RESUMO

Juglone (5 - hydroxy - 1, 4 - naphthalene diketone) is a kind of natural naphthoquinone, present in the roots, leaves, nut-hulls, bark and wood of walnut trees. Recent studies have found that Juglone has special significance in the treatment of cancer, which plays a significant role in the resistance of cancer cell proliferation, induction of cancer cell apoptosis, induction of autophagy, anti-angiogenesis and inhibition of cancer cell migration and invasion, etc. Additionally, its derivatives also play a tumor suppressive effect. In conclusion, Juglone and its derivatives have been identified as effective anticancer drugs. This paper reviews action mechanisms of Juglone and its derivatives in cancer treatment.


Assuntos
Peptidilprolil Isomerase de Interação com NIMA/antagonistas & inibidores , Naftoquinonas/farmacologia , Neoplasias/patologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA Polimerase Dirigida por DNA/efeitos dos fármacos , Humanos , Naftoquinonas/química , Neovascularização Patológica , Espécies Reativas de Oxigênio
8.
Artigo em Inglês | MEDLINE | ID: mdl-34861554

RESUMO

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.


Assuntos
Lagomorpha , Fosfatidilinositol 3-Quinases , Animais , Perfilação da Expressão Gênica , Hipóxia/genética , Hipóxia/metabolismo , Lagomorpha/genética , Lagomorpha/metabolismo , Pulmão/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo
9.
Orthop Surg ; 14(1): 119-128, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34898037

RESUMO

OBJECTIVE: To develop a new method to restore hip rotation center exactly and rapidly in total hip arthroplasty (THA) with the assistance of three dimensional (3D) printing technology and evaluate its clinical and radiological outcomes. METHODS: From March 2014 to July 2018, a total of 17 patients (five hips of four men and 16 hips of 13 women) with end-stage osteoarthritis secondary to developmental dysplasia of the hip who underwent THA were analyzed and followed up retrospectively. The average age is 58.00 ± 8.12 years (range from 45 to 71 years). Simulated operations were performed on 3D printed hip models for preoperative planning. The morphology of Harris fossa and acetabular notches were recognized and restored to locate the acetabular center. The size of bone defect was measured by the bone wax method. The agreement on the size of acetabular cup and bone defect between simulated operations and actual operations were analyzed. Harris Hip Score (HHS) was used to evaluate the recovery of hip joint function. The vertical distance and horizontal distance of the rotation center on the pelvis plain radiograph were measured, which were used to assess the efficacy of restoring hip rotation center and acetabular cup migration. RESULTS: The mean sizes of bone defect in simulated operations and THA were 4.58 ± 2.47 cm2 and 4.55 ± 2.57 cm2 respectively. There was no significant difference statistically between the sizes of bone defect in simulated operations and the actual sizes of bone defect in THA (t = 0.03, P = 0.97). The sizes of the acetabular cup of simulated operations on 3D print models showed a high rate of coincidence with the actual sizes in the operations (ICC = 0.93). All 17 patients were available for clinical and radiological follow-up. The average follow-up time was 18.35 ± 6.86 months (range, 12-36 months. The average HHS of the patients was improved from (38.33 ± 6.07) preoperatively to the last follow-up (88.61 ± 3.44) postoperatively. The mean vertical and horizontal distances of hip rotation center on the pelvic radiographs were restored to 15.12 ± 1.25 mm and 32.49 ± 2.83 mm respectively. No case presented dislocation or radiological signs of loosening until last follow-up. CONCLUSIONS: The application of 3D printing technology facilitates orthopedists to recognize the morphology of Harris fossa and acetabular notches, locate the acetabular center and restore the hip rotation center rapidly and accurately.


Assuntos
Artroplastia de Quadril/métodos , Displasia do Desenvolvimento do Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Modelagem Computacional Específica para o Paciente , Impressão Tridimensional , Idoso , Displasia do Desenvolvimento do Quadril/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/etiologia , Planejamento de Assistência ao Paciente , Projetos Piloto , Rotação
10.
Biomed Pharmacother ; 145: 112397, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34798468

RESUMO

Oleanolic acid (OA, 3 ß - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias/tratamento farmacológico , Ácido Oleanólico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Ácido Oleanólico/análogos & derivados , Transdução de Sinais/efeitos dos fármacos
11.
Turk Neurosurg ; 31(6): 880-887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759171

RESUMO

AIM: To analyze certain magnetic resonance imaging (MRI) features as well as six major genetic biomarkers, investigated their associations, and evaluated their prognostic roles in glioblastomas (GBMs). MATERIAL AND METHODS: Strict criteria included newly diagnosed GBM with optimal treatments. Simple manual imaging characteristics (tumor side, location, enhancement, diameter, depth, radiographic necrosis, and edema) were obtained from preoperative conventional MRI. Furthermore, all the status of the MGMT promoter, Chromosome 1p and 19q, IDH, TERT, and BRAF in tumor tissues were detected. RESULTS: Among 126 inpatients, 60 cases were selected and enrolled in the study. The status of the MGMT promoter was significantly associated with the grade of radiographic necrosis (p=0.033). The rate of 19q deletion was significantly higher in tumors with the ring-shaped peritumoral edema (PTE) (p=0.035) and in tumors with the ring-enhanced trait (p=0.023). Univariate analysis showed that a low PTE index and MGMT promoter methylation were both unfavorable prognostic factors. While the PTE index statistically dropped out, the status of the MGMT promoter and the depth of the tumor were observed to be independent prognostic factors in multivariate analysis. CONCLUSION: Based on simple neuroimaging metrics, novel connections between features of preoperative conventional MRI and status of major genetic biomarkers were observed, especially for the MGMT promoter and 19q.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Humanos , Imageamento por Ressonância Magnética , Prognóstico , Proteínas Supressoras de Tumor/genética
12.
Ann Palliat Med ; 10(5): 5813-5817, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32787377

RESUMO

It is essential for acute ischemic stroke (AIS) patients to receive timely revascularization. However, intravenous thrombolysis (IVT) is not recommended for AIS patients with warfarin associated hypocoagulability. Meanwhile, monotherapy of coagulation factors or vitamin K is unable to reverse anticoagulation of warfarin in emergency. Thus, developing an effective IVT strategy poses a challenging task for these fragile population. Herein, an 82-year-old male, on regular administration with warfarin because of nonvalvular atrial fibrillation (NVAF), suffered from AIS and had an elevated international normalized ratio value of 1.72 and prolonged prothrombin time of 18.2 s at stroke onset. For normalizing INR, combination of 4 factor prothrombin complex concentrate, fresh frozen plasma and vitamin K1 were administrated. Finally, the patient successfully received recombinant tissue plasminogen activator (rt-PA), with an obviously neurological improvement. This case shows a feasible role of IVT therapy with rt-PA after reversal of coagulation regarding AIS patients with warfarin-related hypocoagulability.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Humanos , Masculino , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Varfarina/uso terapêutico
13.
Steroids ; 166: 108774, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33285175

RESUMO

Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte).


Assuntos
Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Amônio , Linhagem Celular Tumoral , Humanos
14.
Ann Saudi Med ; 40(3): 183-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32493029

RESUMO

BACKGROUND: Mesenteric traction syndrome (MTS), which is characterized by arterial hypotension and tachycardia following mesenteric traction (MT), frequently occurs during abdominal surgery. Dexmedetomidine, commonly used in general anesthesia during major surgery, has a sympatholytic effect and attenuates the compensatory response to hypotension. OBJECTIVE: Assess the effect of dexmedetomidine on hypotension following mesenteric traction. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Department of Anesthesiology, Zhenjiang First People's Hospital in China. PATIENTS AND METHODS: Patients were randomly divided into three groups. Dexmedetomidine, 0.5 or 1.0 µg/kg, was intravenously administered over 15 minutes before skin incision followed by a maintenance rate of 0.5 µg/kg/h in groups D1 and D2, respectively; saline was administered in group C. MAIN OUTCOME MEASURE(S): The duration of hypotension, heart rate and plasma norepinephrine level in patients with MTS were recorded within 60 minutes following MT. SAMPLE SIZE: 75 patients. RESULTS: The duration of hypotension in the MTS patients in group D1 and D2 was significantly longer than that in groups C (D1 vs. C, P<.05; D2 vs. C, P<.01). Significantly more phenylephrine was required to treat hypotension in group D1 and D2 than was required for patients in group C (P<.05). The increase in heart rate during the first 15 minutes of MT in group D2 was significantly attenuated compared to that in group C (P<.0083). The increases in norepinephrine levels during the first 15 minutes of MT in group C were significantly higher than those in groups D1 and D2 (P<.0167). CONCLUSION: Adjunctive dexmedetomidine in general anesthesia aggravates hypotension during MTS in open total gastrectomy. LIMITATIONS: Postoperative complications were not evaluated. CONFLICT OF INTEREST: None.


Assuntos
Dexmedetomidina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/fisiopatologia , Complicações Intraoperatórias/fisiopatologia , Mesentério/cirurgia , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/etiologia , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Síndrome , Taquicardia/etiologia , Taquicardia/fisiopatologia
15.
Oncol Res ; 28(4): 423-438, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32331534

RESUMO

Although oxaliplatin serves as one of the first-line drugs prescribed for treating colorectal cancer (CRC), the therapeutic effect is disappointing due to drug resistance. So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In this study, we found the chemoresistance in oxaliplatin-resistant HCT116 cells (HCT116/OXA) was mediated by the upregulation of ERCC1 expression. In addition, the acquisition of resistance induced epithelialmesenchymal transition (EMT) as well as the Slug overexpression. On the contrary, Slug silencing reversed the EMT phenotype, decreased ERCC1 expression, and ameliorated drug resistance. Further mechanistical studies revealed the enhanced Slug expression resulted from the activation of AKT/glycogen synthase kinase 3 (GSK3) signaling. Moreover, in CRC patients, coexpression of Slug and ERCC1 was observed, and increased Slug expression was significantly correlated with clinicopathological factors and prognosis. Taken together, the simultaneous inhibition of the AKT/GSK3/Slug axis may be of significance for surmounting metastasis and chemoresistance, thereby improving the therapeutic outcome of oxaliplatin.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Oxaliplatina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Endonucleases/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/genética , Células HCT116 , Humanos , Fenótipo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição da Família Snail/genética , Regulação para Cima/efeitos dos fármacos
16.
Cancer Sci ; 111(1): 84-97, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31774615

RESUMO

Although accumulating evidence has indicated the intimate association between epithelial-mesenchymal transition (EMT) and acquired resistance to chemotherapy for colorectal cancer (CRC), the underlying mechanisms remain elusive. Herein, we reported that Snail, a crucial EMT controller, was upregulated in CRC tissues. Colorectal cancer cells overexpressing Snail were found to be more resistant to 5-fluorouracil (5-Fu). Mechanistic studies reveal that Snail could increase the expression of ATP-binding cassette subfamily B member 1 (ABCB1) rather than the other 23 chemoresistance-related genes. Additionally, knockdown of ABCB1 significantly attenuated Snail-induced 5-Fu resistance in CRC cells. Oxaliplatin increased Snail and ABCB1 expression in CRC cells. Snail and ABCB1 were upregulated in 5-Fu-resistant HCT-8 (HCT-8/5-Fu) cells and inhibition of Snail decreased ABCB1 in HCT-8/5-Fu cells. These results confirm the vital role played by ABCB1 in Snail-induced chemoresistance. Further investigation into the relevant molecular mechanism revealed Snail-mediated ABCB1 upregulation was independent of ß-catenin, STAT3, PXR, CAR and Foxo3a, which are commonly involved in modulating ABCB1 transcription. Instead, Snail upregulated ABCB1 transcription by directly binding to its promoter. Clinical analysis confirms that increased Snail expression correlated significantly with tumor size (P = .018), lymph node metastasis (P = .033), distant metastasis (P = .025), clinical stage grade (P = .024), and poor prognosis (P = .045) of CRC patients. Moreover, coexpression of Snail and ABCB1 was observed in CRC patients. Our study revealed that direct regulation of ABCB1 by Snail was critical for conferring chemoresistance in CRC cells. These findings unraveled the mechanisms underlying the association between EMT and chemoresistance, and provided potential targets for CRC clinical treatment.


Assuntos
Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fatores de Transcrição da Família Snail/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Transdução de Sinais/genética , Regulação para Cima/genética
17.
Mol Med Rep ; 21(2): 607-614, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789412

RESUMO

Ventilator­induced lung injury (VILI) is a life­threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of VILI remains to be elucidated. In the present study, it was revealed that the calcineurin/NFATc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of VILI. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with VILI, and NFATc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of NFATc4 and lung injury were prevented by a calcineurin inhibitor (CsA). Thus, the present results highlighted the critical role of the calcineurin/NFATc4 signaling pathway in VILI and suggest that this pathway coincides with the release of ICAM­1, VCAM­1, TNF­α and IL­1ß.


Assuntos
Calcineurina/metabolismo , Fatores de Transcrição NFATC/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Animais , Calcineurina/genética , Inibidores de Calcineurina/farmacologia , Núcleo Celular/metabolismo , Edema/complicações , Edema/metabolismo , Inflamação/complicações , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Fatores de Transcrição NFATC/antagonistas & inibidores , Fatores de Transcrição NFATC/genética , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Peroxidase/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/enzimologia , Lesão Pulmonar Induzida por Ventilação Mecânica/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
18.
Biochem Biophys Res Commun ; 513(4): 1005-1012, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31005256

RESUMO

Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is thought to be an essential component of inflammatory response. However, its role and mechanism in regulating acute lung injury (ALI) and macrophages activation are not well characterized. In our study, we observe that blockade of TRPV4 using GSK2193874 or HC-067047 greatly improve the pneumonedema, the lung pathologic changes, the up-regulation of proinflammatory cytokines and the neutrophil infiltration in LPS-induced lung injury. In vitro, knockdown of TRPV4 in macrophages reduces the levels of pro-inflammatory cytokines, ROS production, Ca2+ concentration in cytoplasma and the activation of calcineurin/NFATc3 signaling. Importantly, change of extracellular Ca2+ in culture medium prevents LPS-induced NFATc3 nuclear translocation, up-regulation of proinflammatory cytokines and ROS production in macrophages. Inhibition of calcineurin with cyclosporine A, FK506 down-regulates the levels of NFATc3 nuclear translocation and proinflammatory cytokines expression. Our results demonstrate that TRPV4-dependent Ca2+ influx contributes to LPS-induced macrophage activation by calcineurin-NFATc3 pathway.


Assuntos
Calcineurina/metabolismo , Inflamação/induzido quimicamente , Fatores de Transcrição NFATC/metabolismo , Transdução de Sinais , Canais de Cátion TRPV/fisiologia , Lesão Pulmonar Aguda , Animais , Cálcio/metabolismo , Células Cultivadas , Humanos , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Morfolinas/farmacologia , Piperidinas/farmacologia , Pirróis/farmacologia , Quinolinas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores
19.
PLoS One ; 13(11): e0206345, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30383865

RESUMO

Although the phylogenetic framework of Davalliaceae is known, the classification of Chinese Davalliaceae is still controversial. In this study, a molecular phylogenetic tree of 60 accessions, including 29 species produced in China, was constructed using five plastid DNA markers-atpB, atpB-rbcL, rbcL, rbcL-accD, and accD. New data on studied specimens, field investigations, and scanning electron microscopy analysis of leaf epidermis and spores were used to reclassify Chinese Davalliaceae. The taxonomic position of Davallia canariensis was confirmed based on new evidence and a new key to sections of Chinese Davalliaceae was proposed. The taxonomically controversial genus Paradavallodes was confirmed as a polyphyletic group, and it was assigned to Davallia sect. Trogostolon and Davallia sect. Davallodes. Further, species endemic to China were delimited, 21 species were admitted to six sections of Davallia, two new combinations were proposed, two new synonyms were defined and a new key to Chinese species of Davalliaceae was presented.


Assuntos
Marcadores Genéticos , Traqueófitas/anatomia & histologia , Traqueófitas/classificação , Traqueófitas/genética , Animais , China , DNA de Plantas/análise , DNA de Plantas/genética , Microscopia Eletrônica de Varredura , Filogenia , Folhas de Planta/anatomia & histologia , Folhas de Planta/ultraestrutura , Plastídeos/genética , Análise de Sequência de DNA/métodos , Traqueófitas/ultraestrutura
20.
J Orthop Translat ; 15: 59-69, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30310766

RESUMO

OBJECTIVE: The objective of this study was to evaluate the usefulness of T2 high signal intensity (T2-HSI) and decreased anteroposterior diameter (APD), diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in evaluating postoperative cervical cord function. METHODS: The study included 57 postoperative cervical spondylotic myelopathy patients. Clinical evaluation and functional recovery assessments were performed using the modified Japanese Orthopaedic Association (mJOA) score and recovery rate. The presence of T2-HSI and decreased APD was recorded for exploring the relevance. Spearman correlation was applied to investigate the relationships between DTI and NODDI metrics and mJOA score. Multiple comparisons of T2 signal intensity, APD and diffusion metrics were evaluated by using multiple linear regression. RESULTS: Only the recovery rate was significantly different between T2-HSI and non-T2-HSI (nT2-HSI) patients (χ2 = 4.466, p = 0.045). Significant differences were not observed between cervical cords with and without decreased APD. Diffusion metrics, including fractional anisotropy (p = 0.0005), mean diffusivity (p = 0.0008), radial diffusivity (p = 0.0003) and intracellular volume fraction (p = 0.001), were significantly correlated with mJOA score. The ability of T2 signal intensity (p = 0.421) and APD (p = 0.420) to evaluate the postoperative function was inferior to that of fractional anisotropy (p = 0.002), mean diffusivity (p = 0.001), radial diffusivity (p = 0.001) and intracellular volume fraction (p = 0.004). CONCLUSION: Conventional magnetic resonance imaging signs could be considered as a reference to make an approximate assessment, whereas DTI and NODDI could be better quantitative tools for evaluating the postoperative function and may help in interpreting residual symptoms. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: DTI and NODDI could provide reliable postoperative evaluation and analysis for cervical spondylotic myelopathy patients.

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