Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Sci Total Environ ; 947: 174483, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969139

RESUMO

Suspended solids concentration (SSC) in a river is closely relevant to river water turbidity. Investigation of their relationship in this study is accompanied by observed turbidity and SSC values, which were obtained from the testing results of water samples and monitored conditions in streamflow. The water samples were collected from two observation stations with a broad range of sediment concentrations in the Lai Chi Wo catchment in Hong Kong, China. We classified the target rainfall events into single-peak event type and dual-peak event type for a distinguished discussion of the relationship between SSC and turbidity in this study. At a finer classification, each event is separated into defined processes for the analysis, where two main processes refer to the periods that SSC rises from a normal state to a peak state first and the followed periods that SSC recesses to ordinary status gradually. It is advised by the analysis results that the estimation of SSC through turbidity values should be based on the same rainfall types for the upstream station. However, the results show that the classification of rainfall types does not need to take downstream areas into consideration. Furthermore, current research implies that the individual established connections between SSC and turbidity value at different stages (particularly referring to the rising period and recessing period) could be applied to estimate SSC at the same station via continuous turbidity values for both this and other ungauged stations with similar topographical features in the future. Meanwhile, this research approach provides new insight exploring various behaviors of sediments at different stages during an integral rainfall event. A comparison of distinguished performances of sediment during corresponding stages in a rainfall event makes contributions to diverse relationship between SSC and turbidity in the mountainous river.

2.
Sci Rep ; 13(1): 20382, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37989855

RESUMO

Necroptosis is a recently discovered apoptotic mechanism that has been linked to tumor formation, prognosis, and treatment response. However, the relationship between the TME and NRGs remains unclear. In this study, we analyzed the expression patterns of NRGs in 769 HNSCC cases from two distinct data sets. Our findings revealed distinct genetic groups and a correlation between patient clinical features, prognosis, TME cell infiltration characteristics, and NRG alterations. We then developed an NRG model to predict OS and confirmed its accuracy in predicting OS in HNSCC patients. Moreover, we have devised a precise nomogram that enhances the clinical utility of the NRG model substantially. The low-risk group had a better OS, and they were associated with immune suppression, more mutated genes, and higher TIDE scores. The risk score also had a significant correlation with the CSC index and susceptibility to anti-tumor agents. Our study provides insights into how NRGs affect prognosis, clinically significant features, TME, and immunotherapy response in HNSCC. With a better knowledge of NRGs in HNSCC, we could assess the prognosis and develop immunotherapy regimens that are more successful at opening up new doors.


Assuntos
Neoplasias de Cabeça e Pescoço , Necroptose , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Necroptose/genética , Prognóstico , Imunoterapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia
3.
Sci Total Environ ; 863: 160759, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36509276

RESUMO

River turbidity is an important factor in evaluating environmental water quality, and turbidity dynamics can reflect water sediment changes. During rainfall periods, specifically in mountainous areas, river turbidity varies dramatically, and knowledge of spatiotemporal turbidity variations in association with rainfall features and farming activities is valuable for soil erosion prevention and catchment management. However, due to the difficulties in collecting reliable field turbidity data during rainstorms at a fine temporal scale, our understanding of the features of turbidity variations in mountainous rivers is still vague. This study conducted field measurements of hydrological and environmental variables in a mountainous river, the Lai Chi Wo river, in Hong Kong, China. The study results revealed that variations of turbidity graphs during rainstorms closely match variations of streamflow hydrographs, and the occurrence of the turbidity peaks and water level peaks are almost at the same time. Moreover, the study disclosed that the increasing rates of the turbidity values are closely related to the rainfall intensity at temporal scales of 15 and 20 min, and the impact of farming activities on river turbidity changes is largely dependent on rainfall intensity. In the study area, when the rainfall intensity is larger than 35 mm/hr at a time interval of 15 min, the surface runoff over the farmland would result in higher river water turbidity downstream than that upstream. The study results would enrich our understanding of river water turbidity dynamics at minute scales and be valuable for further exploration of the river water environment in association with turbidity.

4.
Diabetes Res Clin Pract ; 183: 109126, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34742784

RESUMO

AIMS: We focused on BMSC-derived exosomal lncRNA KLF3-AS1 and its significance in diabetic cutaneous wound healing. METHODS: Potential interaction between KLF3-AS1 and miR-383, miR-383 and VEGFA were predicted using bioinformatic analysis and validated by luciferase reporter, RIP, and FISH assays. The proliferation, apoptosis, migration and tube formation of HUVECs were evaluated by CCK-8, flow cytometry, wound healing, and tube formation assays, respectively. A murine diabetic cutaneous wound model was used to investigate therapeutic effects of exosomal KLF3-AS1 in vivo. Histological alterations in skin tissues were examined using HE, Masson staining, and immunostaining of CD31. RESULTS: BMSC-derived exosomal KLF3-AS1 sufficiently promoted proliferation, migration, and tube formation, while inhibited apoptosis of HUVECs challenged by high glucose. The protective effects of exosomal KLF3-AS1 were achieved at least partially by down-regulating miR-383, and boosting the expression of its target, VEGFA. In vivo, exosomes from KLF3-AS1-expressing BMSCs demonstrated the best effects in promoting cutaneous wound healing in diabetic mice, which were associated with minimal weight loss, increased blood vessel formation, reduced inflammation, decreased miR-383 expression, and up-regulated VEGFA. CONCLUSIONS: Exosomal lncRNA KLF3-AS1 derived from BMSCs induces angiogenesis to promote diabetic cutaneous wound healing.


Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Animais , Proliferação de Células , Diabetes Mellitus Experimental/genética , Fatores de Transcrição Kruppel-Like , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular , Cicatrização/genética
5.
Sensors (Basel) ; 21(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34300539

RESUMO

In various domains of material processing, such as surface cleaning and surface treatment, cavitation phenomenon may become an alternative to traditional methods if this phenomenon is well understood. Due to experimental and mathematical difficulties in theoretical models, it is still a challenge to accurately measure the physical mechanism of the fluid/structure interactions. In this study, we verified the feasibility of using polyvinylidene fluoride (PVDF) sensors to quantitatively measure the under-water pressure wave generated by the collapse of a single cavitation bubble. The electrical signal obtained by PVDF can be converted into pressure information only by using the sensor material parameters provided by the supplier. During the conversion process, only the capacitance of the acquisition chain needs to be additionally measured. At the same time, a high-speed video recording system was used to visualize the evolution of the cavitation bubble. The Gilmore analytical model and an associated wave propagation model were used to simulate the pressure peak of the first collapse of the cavitation bubble. This theoretical pressure was compared with the experimental results. The result showed that, for bubbles with a normalized standoff distance γ larger than 5, the PVDF sensor had the ability to quantitatively measure the pressure wave generated by a single cavitation bubble.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1156-1161, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512459

RESUMO

OBJECTIVE: To investigate the anatomy of anterior and posterior terminal perforators of the peroneal artery and its clinical applications. METHODS: Six lower limb specimens were obtained from 3 fresh cadavers. The anterior and posterior terminal perforators and the perforator of terminal peroneal artery were exposed under surgical microscope, and the distances from the beginning of each perforator branch to the lateral malleolus tip and the external diameter of each perforator were measured. With these anatomical knowledge and contrast-enhanced ultrasound (CEUS) guidance, the pedicle flaps with above-mentioned perforators were rationally selected and precisely designed for 18 patients with skin defects in the ankle and foot region between October 2016 and December 2018. Among the patients, there were 14 males and 4 females, aged 28-62 years, with an average age of 40 years. The area of wound ranged from 4 cm×3 cm to 13 cm×10 cm and the area of skin flap ranged from 5 cm×4 cm to 14 cm×10 cm. The anterior peroneal artery terminal perforator flap were applied in 13 cases and the posterior peroneal artery terminal perforator flap in 5 cases. The donor sites were closed directly in 7 cases and repaired with full thickness skin graft in 11 cases. RESULTS: The distance from the beginning of the anterior terminal perforator to the lateral malleolus tip was (5.1±0.5) cm, the external diameter of the anterior terminal perforator was (1.51±0.05) mm. The distance from the beginning of the posterior terminal perforator to the lateral malleolus tip was (4.9±0.9) cm, the external diameter was (1.78±0.17) mm; the distance from the beginning of the perforator of terminal peroneal artery to the lateral malleolus tip was (1.7±0.7) cm, the external diameter was (0.58±0.12) mm. Clinical application results: The edge of the flap was dark in 2 cases after operation and healed after surgical dressing, and 1 case of wound infection healed gradually after debridement. The other flaps survived and healed by first intention. Three patients underwent plastic surgery at 3 months after operation due to flap swelling. All patients were followed up 3-18 months. During the follow-up period, the flaps had good texture and appearance, and partial recovery of sensation. All cases were assessed by the American Orthopaedic Foot and Ankle Society (AOFAS) score at last follow-up. The results were excellent in 9 cases, good in 6 cases, fair in 2 cases, and poor in 1 case, with the excellent and good rate of 83.3%. CONCLUSION: Further classification of peroneal artery perforators in the lateral malleolus region can improve clinical understanding and be helpful to selection and application of perforator flaps in the lateral malleolus.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Transplante de Pele , Lesões dos Tecidos Moles , Artérias da Tíbia , Adulto , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/normas , Artérias da Tíbia/cirurgia
7.
Eur J Pharmacol ; 862: 172531, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31301310

RESUMO

Bronchial and alveolar epithelial cell apoptosis is a vital step in smoke-induced lung injury. We investigated whether and how microRNA (miRNA) Let-7f-1-3p would regulate smoke-induced apoptosis in bronchial and alveolar epithelial cells. Human small airway epithelial cells (HSAEC) and human pulmonary alveolar epithelial cells (HPAEpiC) were cultured using an air-liquid interface cell culture system. These cells were treated with Let-7f-1-3p agomir or antagomir for 24 h before smoke exposure or sham operation, after which the cells were rinsed and cultured for 24 h before cell viability, apoptosis, cytolysis, Caspase-9/8/3 activity assays, quantitative real-time polymerase chain reaction and Western blot. Bioinformatic and luciferase reporter assays were performed to predict or verify the target gene of Let-7f-1-3p. We found that smoke exposure significantly reduced Let-7f-1-3p expression level in HSAEC and HPAEpiC. Let-7f-1-3p agomir significantly attenuated cell apoptosis, cytolysis and Caspase-3, -8 and -9 activation while rescuing cell viability of smoke-exposed HSAEC and HPAEpiC. Let-7f-1-3p agomir downregulated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL) and B-cell lymphoma-2 (Bcl2)-like protein 11 (Bim) protein level in HSAEC and HPAEpiC. Forkhead box-O1 (FOXO1) was verified as a putative regulatory target of Let-7f-1-3p. Smoke exposure increased FOXO1 mRNA and protein level in HSAEC and HPAEpiC, which was attenuated by Let-7f-1-3p agomir treatment. FOXO1 inhibition by small-molecule drug partially attenuated the increase in smoke-exposed HSAEC and HPAEpiC apoptosis, cytolysis and the decrease in cell viability caused by Let-7f-1-3p antagomir treatment. We concluded Let-7f-1-3p attenuated smoke-induced apoptosis in HSAEC and HPAEpiC by targeting FOXO1.


Assuntos
Células Epiteliais Alveolares/patologia , Apoptose/genética , Proteína Forkhead Box O1/genética , MicroRNAs/metabolismo , Lesão por Inalação de Fumaça/patologia , Células Epiteliais Alveolares/efeitos dos fármacos , Antagomirs/farmacologia , Apoptose/efeitos dos fármacos , Brônquios/citologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Fumaça/efeitos adversos , Lesão por Inalação de Fumaça/induzido quimicamente
8.
J Cell Biochem ; 120(7): 11115-11126, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30701576

RESUMO

Compelling evidence shows that deregulated microRNAs (miRNAs) are important regulators in the progression of melanoma. miR-145-5p has been suggested to exhibit antitumorigenic activity in melanoma. However, the molecular mechanism underlying the biological activity of miR-145-5p in melanoma remains to be further understood. Herein, quantitative real-time polymerase chain reaction was used to examine the miR-145-5p expression in malignant melanoma tissues and cells. The interaction between miR-145-5p and toll-like receptor 4 (TLR4) was explored by bioinformatics analyses, luciferase reporter assay, and Western blot. The effects of miR-145-5p or combined with TLR4 on cell proliferation, colony formation, migration, and invasion abilities were investigated by (4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, colony formation, wound healing, and transwell assays, respectively. The melanoma xenograft tumor models were established to determine the biological activity of miR-145-5p in melanoma in vivo. In addition, the changes of the nuclear factor kappa B (NF-κB) pathway were analyzed by detecting the NF-κB activity and the NF-κB p65 protein level. We observed that the miR-145-5p expression was underexpressed in melanoma tissues and cells. miR-145-5p suppressed the TLR4 expression by binding to its 3'untranslated region in melanoma cells. Moreover, TLR4 overexpression abolished the inhibition of cell proliferation, colony formation, migration, and invasion abilities induced by miR-145-5p in melanoma cells. Meanwhile, miR-145-5p was confirmed to restrain melanoma tumor growth in vivo by targeting TLR4. Furthermore, miR-145-5p overexpression inactivated the NF-κB pathway in melanoma in vitro and in vivo, which was reversed by TLR4 overexpression. We concluded that miR-145-5p hindered the occurrence and metastasis of melanoma cells in vitro and in vivo by targeting TLR4 via inactivation of the NF-κB pathway.

9.
Cell Cycle ; 18(3): 333-345, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30646812

RESUMO

Previous research has shown that microRNA 506 (miR-506) functions as an essential modulator in the development of many biological reactions, including multiple cancers. However, its involvement in cutaneous squamous cell carcinoma (CSCC) has been rarely reported. In the present work, we investigated the molecular mechanism and function of miR-506 in the regulation of CSCC cell viability and metastasis (migration and invasion). We observed that miR-506 expression was upregulated in both CSCC tissues and cell lines, and that decreased miR-506 expression led to repressed tumorigenesis in CSCC cells. Furthermore, flow cytometry revealed that the depletion of miR-506 resulted in decreased proliferation and increased apoptotic levels in CSCC cells. Meanwhile, it was found that miR-506 decreased CSCC cell migration and invasion in vitro. The dual-luciferase reporter assay also revealed that miR-506 targets the 3'-UTRs of p65 and Laminin C1 (LAMC1) for silencing. Silencing of p65 expression counteracted the pro-apoptotic influence of miR-506 depletion in CSCC cells, while inhibition of LAMC1 expression restored the migration and invasion properties of the CSCC cells. Therefore, the results provide evidence for the need to probe the biological and molecular mechanisms behind the development and progression of CSCC and may lead to novel treatment CSCC strategies.


Assuntos
Carcinoma de Células Escamosas/genética , Laminina/genética , MicroRNAs/metabolismo , Neoplasias Cutâneas/genética , Fator de Transcrição RelA/genética , Regiões 3' não Traduzidas , Animais , Apoptose , Carcinogênese , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Inativação Gênica , Humanos , Laminina/metabolismo , Camundongos Endogâmicos BALB C , MicroRNAs/antagonistas & inibidores , Invasividade Neoplásica , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fator de Transcrição RelA/metabolismo
10.
Mol Biosyst ; 13(10): 2145-2151, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28832060

RESUMO

The recognition and association between the Ca2+/calmodulin-activated protein kinase II-α (CaMKIIα) and the multi-PDZ domain protein 1 (MUPP1) plays an important role in the sperm acrosome reaction and human fertilization. Previously, we have demonstrated that the MUPP1 PDZ11 domain is the primary binding partner of the CaMKIIα C-terminal tail, which can be targeted by a rationally designed sia peptide with nanomolar affinity. Here, we further introduced an orthogonal noncovalent interaction (ONI) system between a native hydrogen bond and a designed halogen bond across the complex interface of the PDZ11 domain with the sia [Asn-1Phe] peptide mutant, where the halogen bond was formed by substituting the o-hydrogen atom of the benzene ring of the peptide Phe-1 residue with a halogen atom (F, Cl, Br or I). Molecular dynamics simulations and high-level theoretical calculations suggested that bromine (Br) is a good compromise between the halogen-bonding strength and steric hindrance effect due to introduction of a bulkier halogen atom into the tightly packed complex interface. Fluorescence spectroscopy assays revealed that the resulting o-Br-substituted peptide (Kd = 18 nM) exhibited an ∼7.6-fold affinity increase relative to its native counterpart (Kd = 137 nM). In contrast, the p-Br-substituted peptide, a negative control that is unable to establish the ONI according to structure-based analysis, has decreased affinity (Kd = 210 nM) upon halogenation.


Assuntos
Proteínas de Transporte/metabolismo , Fertilização/genética , Fertilização/fisiologia , Humanos , Ligação de Hidrogênio , Proteínas de Membrana , Simulação de Dinâmica Molecular , Peptídeos/metabolismo , Proteínas/química
11.
J Cell Biochem ; 118(10): 3511-3519, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28374893

RESUMO

A number of miRNAs associated with wound repair have been identified and characterized, but the mechanism has not been fully clarified. MiR-21 is one of wound-related lncRNAs, and the study aimed to explore the functional involvement of miR-21 and its concrete mechanism in wound healing. In this study, the rat model of skin wounds was established. The expression of miR-21, PTEN and related molecules of wound tissues or cells was determined by quantitative real-time PCR and Western blot, respectively. The regulatory role of miR-21 on PTEN was examined by luciferase reporter gene assay. Flow cytometry assay was applied to measure cell number changes. MiR-21 was upregulated at 6, 24, 48, 72 h after model establishment, and the increase reached a maximum at 24 h in wound tissues. MMP-9 expression presented the same tread as miR-21 and was significantly enhanced within 6 h of wound formation, and then remained to be increased to the maximum at 24 h. The increase of miR-21 was accompanied by the increase of cell total number and DCs ratio in wound fluids. MiR-21 overexpression significantly improved the healing of skin wounds and increased the ratio of DCs in rats. The results of using FL confirmed that miR-21 overexpression obviously promoted DCs differentiation. Additionally, miR-21 could activate AKT/PI3K signaling pathway via inhibition of PTEN. MiR-21 contributes to wound healing via inhibition of PTEN that activated AKT/PI3K signaling pathway to increase DCs. J. Cell. Biochem. 118: 3511-3519, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Células Dendríticas/metabolismo , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais , Pele/metabolismo , Cicatrização , Animais , Células Dendríticas/patologia , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Pele/patologia , Regulação para Cima
12.
Int J Surg ; 32: 109-15, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27353849

RESUMO

INTRODUCTION: Currently there is no consensus on what is the optimal method for monitoring free flaps. Our meta-analysis compared the free flap success and salvage rates of Cook-Swartz Implantable Doppler monitoring with clinical monitoring to gain insight into the relative benefit of these systems. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until January 16, 2016. Search terms included free flap surgery, free flap microsurgery and implantable Doppler. Studies were included if they involved the comparison of Cook-Swartz Doppler and clinical assessment for monitoring free flap function. Studies using free flap monitoring as an outcome measure for drug treatment were also excluded. Sensitivity analysis using the leave-one-out approach was used to assay the reliability of the findings. RESULTS: Initial search identified 14 studies, of which five studies were included in the meta-analysis. Cook-Swartz Doppler had significantly better rate of free flap success and salvage than clinical monitoring methods (P values ≤ 0.006). Data did not markedly changed when each study was removed in turn, showing reliability of the findings. DISCUSSION: The Cook-Swartz Doppler as a monitoring method may result in a higher rate of free flap success and salvaging but also a greater frequency of false positives than conventional methods. Our analysis is limited by designs of included studies and by heterogeneity of clinical monitoring techniques. CONCLUSIONS: More studies are needed to evaluate if Cook-Swartz Doppler can be used alone, or to be better used as an adjunctive technique to complement the clinical method of monitoring.


Assuntos
Retalhos de Tecido Biológico/irrigação sanguínea , Fluxometria por Laser-Doppler , Monitorização Ambulatorial/métodos , Cuidados Pós-Operatórios/métodos , Humanos , Fluxometria por Laser-Doppler/instrumentação , Microcirurgia/métodos , Próteses e Implantes , Reprodutibilidade dos Testes , Terapia de Salvação
13.
Amino Acids ; 48(6): 1509-21, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26984442

RESUMO

The recognition and association between Ca(2+)/calmodulin-activated protein kinase II-α (CaMKIIα) and multi-PDZ domain protein 1 (MUPP1) plays an important role in sperm acrosome reaction and human fertilization, which is mediated by the binding of CaMKIIα's C-terminal tail to one or more PDZ domains of the scaffolding protein MUPP1. In this study, we attempt to identify the CaMKIIα-interacting MUPP1 PDZ domains and to design peptide ligands that can potently target and then competitively disrupt such interaction. Here, a synthetic biology approach was proposed to systematically characterize the structural basis, energetic property, dynamic behavior and biological implication underlying the intermolecular interactions between the C-terminal peptide of CaMKIIα and all the 13 PDZ domains of MUPP1. These domains can be grouped into four clusters in terms of their sequence, structure and physiochemical profile; different clusters appear to recognize different classes of PDZ-binding motifs. The cluster 3 includes two members, i.e. MUPP1 PDZ 5 and 11 domains, which were suggested to bind class II motif Φ-X-Φ(-COOH) of the C-terminal peptide SGAPSV(-COOH) of CaMKIIα. Subsequently, the two domains were experimentally measured as the moderate- and high-affinity binders of the peptide by using fluorescence titration (dissociation constants K d = 25.2 ± 4.6 and 0.47 ± 0.08 µM for peptide binding to PDZ 5 and 11, respectively), which was in line with theoretical prediction (binding free energies ΔG total = -7.6 and -9.2 kcal/mol for peptide binding to PDZ 5 and 11, respectively). A systematic mutation of SGAPSV(-COOH) residues suggested few favorable amino acids at different residue positions of the peptide, which were then combined to generate a number of potent peptide mutants for PDZ 11 domain. Consequently, two peptides (SIAPNV(-COOH) and SIVMNV(-COOH)) were identified to have considerably improved affinity with K d increase by ~tenfold relative to wild type peptide. Thus, the two peptides are considered as promising lead entities to develop therapeutic molecular agents with high efficacy and specificity to target CaMKIIα-MUPP1 interaction. Other five designed peptides (SILPSV(-COOH), SGLPNV(-COOH), SIVMSV(-COOH), SIVPNV(-COOH) and SIAMNV(-COOH)) possessed comparable affinity with the wild type, and they may be further optimized to obtain higher potency.


Assuntos
Proteínas de Transporte/química , Fertilização , Simulação de Dinâmica Molecular , Peptídeos/química , Proteínas/química , Proteínas de Transporte/metabolismo , Humanos , Proteínas de Membrana , Domínios PDZ , Peptídeos/farmacologia , Proteínas/metabolismo
14.
Pharmacol Rep ; 68(1): 7-11, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26721344

RESUMO

BACKGROUND: ß-Elemene is a natural anticancer compound extracted from the Chinese medicinal herb Curcuma Wenyujin. This study was done to determine the effect of ß-elemene on the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and associated molecular mechanisms. METHODS: RA-FLS were treated for 72h with ß-elemene at 10-200µg/ml and cell viability and apoptotic changes were examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was checked. RESULTS: We found that ß-elemene significantly inhibited the viability and promoted apoptosis of RA-FLS in a concentration-dependent fashion. ß-Elemene-treated FLS showed a significant decline in mitochondrial membrane potential, an accumulation of cytochrome c in the cytosol, and increased activities of caspase-9 and caspase-3. ß-Elemene treatment caused an enhancement of p38 MAPK phosphorylation and ROS production. The pro-apoptotic activity of ß-elemene was significantly reversed by pretreatment with the p38 inhibitor SB203580 or ROS inhibitor N-acetyl-l-cysteine. CONCLUSIONS: Taken together, ß-elemene is effective in inducing mitochondrial apoptosis of RA-FLS, which is mediated through induction of ROS formation and p38 MAPK activation. ß-Elemene may thus have therapeutic benefits for RA.


Assuntos
Artrite Reumatoide/enzimologia , Fibroblastos/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Membrana Sinovial/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Artrite Reumatoide/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Sesquiterpenos/química , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia
15.
Biochem Biophys Res Commun ; 460(2): 205-9, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25769956

RESUMO

The aim of this study is to explore the effect of zerumbone, a natural sesquiterpene isolated from Zingiber zerumbet Smith, on high glucose-induced cytotoxicity in pancreatic ß cells. INS-1 rat pancreatic ß cells were treated with 33 mM glucose with or without different concentrations of zerumbone and cell viability and apoptosis were assessed. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling in the action of zerumbone was examined. Notably, zerumbone significantly (P < 0.05) prevented the reduction of cell viability induced by high glucose. Such protection was in a concentration-dependent fashion up to 60 µM of zerumbone. Annexin-V/propidium iodide staining analysis showed that zerumbone impaired the apoptotic response of high glucose-treated INS-1 cells, which was coupled with a significant decline in cleaved caspase-3 and caspase-9. Pretreatment with the ROS inhibitor N-acetylcysteine abrogated the phosphorylation of p38 and JNK induced by high glucose. Zerumbone significantly (P < 0.05) decreased the generation of ROS and the phosphorylation of p38 and JNK MAPKs in high glucose-treated INS-1 cells. Pharmacological activation of p38 and JNK with anisomycin reversed the anti-apoptotic effect of zerumbone. Additionally, simultaneous inhibition of p38 and JNK significantly (P < 0.05) reduced the apoptotic response in high glucose-treated INS-1 cells. In conclusion, zerumbone confers protection against high glucose-induced apoptosis of INS-1 pancreatic ß cells, largely through interfering with ROS production and p38 and JNK activation. Zerumbone may have potential therapeutic effects against hyperglycemia-induced ß cell damage in diabetes.


Assuntos
Apoptose/efeitos dos fármacos , Glucose/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Ilhotas Pancreáticas/enzimologia , Ilhotas Pancreáticas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ratos
16.
J Int Med Res ; 42(3): 737-43, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24717407

RESUMO

OBJECTIVE: To compare the short-term efficacy and safety profile of the S-1 + irinotecan + oxaliplatin (TIROX) and docetaxel + cisplatin + flurouracil (DCF) anticancer regimens in patients with advanced gastric cancer. METHODS: Patients with recurrent or metastatic gastric cancer diagnosed by pathology were randomly divided into two groups to receive six cycles of either the TIROX regimen (21-day cycle) or the DCF regimen (21-day cycle). After six chemotherapy cycles, the short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines and adverse reactions were recorded according to National Cancer Institute Common Toxicity Criteria 2.0 standards. RESULTS: A total of 60 patients were enrolled in the study. The response rate (complete response + partial response) was significantly higher in the TIROX group (18/30 patients; 60.0%) compared with the DCF group (10/30 patients; 33.3%). The rates of grade III-IV leucopenia and neurotoxicity were significantly higher in the TIROX group than the DCF group. CONCLUSION: The TIROX regimen was effective for the treatment of advanced gastric cancer, but it was associated with leucopenia and neurotoxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucopenia/etiologia , Síndromes Neurotóxicas/etiologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Docetaxel , Esquema de Medicação , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucopenia/fisiopatologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/fisiopatologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ácido Oxônico/administração & dosagem , Estudos Prospectivos , Recidiva , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Tegafur/administração & dosagem , Resultado do Tratamento
17.
J Int Med Res ; 42(1): 191-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24398758

RESUMO

OBJECTIVE: To compare the therapeutic effects and adverse reactions of pemetrexed and docetaxel as salvage chemotherapy in patients with nonsmall-cell lung cancer (NSCLC) after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). METHODS: In this randomized Phase 2 trial, patients with NSCLC who had previously failed EGFR-TKI therapy were randomized to receive intravenous pemetrexed (500 mg/m(2) for 21 days [one cycle]) or docetaxel (75 mg/m(2) for 21 days [one cycle]). Therapeutic effects were evaluated according to Response Evaluation Criteria in Solid Tumours standards and adverse effects were evaluated according to the US National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: There was no statistically significant difference in disease control rate, response rate, median survival and 1-year survival between treatment groups. Rates of nausea, myelosuppression, renal damage and hair loss were significantly higher in the docetaxel group than the pemetrexed group. CONCLUSION: Pemetrexed is effective and well tolerated as salvage chemotherapy in patients with NSCLC after EGFR-TKI failure and may be a suitable therapeutic option in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Docetaxel , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Pemetrexede , Terapia de Salvação , Taxoides/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA