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1.
Foods ; 13(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38201118

RESUMO

High-methoxyl apple pectin (AP) derived from apple was employed as the main ingredient facilitating rheological modification features in developing dysphagia-friendly fluidized alimentary matrices. Xanthan gum (XG) was also included as a composite counterpart to modify the viscoelastic properties of the thickened system under different thermal processes. The results indicate that AP is extremely sensitive to thermal processing, and the viscosity is greatly depleted under a neutral pH level. Moreover, the inclusion of calcium ions echoed the modification effect on the rheological properties of AP, and both the elastic property and viscosity value were promoted after thermal processing. The modification effect of viscoelastic properties (G' and G″) was observed whne XG was incorporated into the composite formula. Increasing the XG ratio from 7:3 to 6:4 (AP:XG) triggers the rheological transformation from a liquid-like form to a solid-like state, and the viscosity value shows that the AP-XG composite system exhibits better thermal stability after thermal processing. The ambient modifiers of pH (pH < 4) and calcium chloride concentration (7.5%) with an optimal AP-XG ratio of 7:3 led to weak-gel-like behavior (G″ < G'), helping to maintain the texture properties of dysphagia-friendly features similar to those prior to the thermal processing.

2.
Biomedicines ; 10(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36140274

RESUMO

Discoidin domain receptor 1 (DDR1) is a collagen receptor that belongs to the receptor tyrosine kinase family. We have previously shown that DDR1 plays a crucial role during bone development, resulting in dwarfism and a short stature in osteoblast-specific knockout mice (OKO mice). However, the detailed pathophysiological effects of DDR1 on bone development throughout adulthood have remained unclear. This study aims to identify how DDR1 regulates osteoblast and osteocyte functions in vivo and in vitro during bone development in adulthood. The metabolic changes in bone tissues were analyzed using Micro-CT and immunohistochemistry staining (IHC) in vivo; the role of DDR1 in regulating osteoblasts was examined in MC3T3-E1 cells in vitro. The Micro-CT analysis results demonstrated that OKO mice showed a 10% reduction in bone-related parameters from 10 to 14 weeks old and a significant reduction in cortical thickness and diameter compared with flox/flox control mice (FF) mice. These results indicated that DDR1 knockout in OKO mice exhibiting significant bone loss provokes an osteopenic phenotype. The IHC staining revealed a significant decrease in osteogenesis-related genes, including RUNX2, osteocalcin, and osterix. We noted that DDR1 knockout significantly induced osteoblast/osteocyte apoptosis and markedly decreased autophagy activity in vivo. Additionally, the results of the gain- and loss-of-function of the DDR1 assay in MC3T3-E1 cells indicated that DDR1 can regulate the osteoblast differentiation through activating autophagy by regulating the phosphorylation of the mechanistic target of rapamycin (p-mTOR), light chain 3 (LC3), and beclin-1. In conclusion, our study highlights that the ablation of DDR1 results in cancellous bone loss by regulating osteoblast/osteocyte autophagy. These results suggest that DDR1 can act as a potential therapeutic target for managing cancellous bone loss.

3.
BMJ Open Qual ; 11(3)2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35940697

RESUMO

BACKGROUND: Surgery is recommended within 48 hours of hip fractures for better perioperative outcomes. Yet, such targets still commonly remain a challenge. Our institution is no exception.As part of a hospital-wide initiative, our anaesthesia department focused on improving perioperative processes with aims to reduce the time to first anaesthesia consult and surgery for hip fracture patients. Acknowledging multiple causes for surgical delay, we decided first to address anaesthesia-specific factors-(a) first anaesthetist contact usually happens after surgery is offered which leaves a short runway for preoptimisation, (b) this is compounded by varying degrees of anaesthetist involvement for follow-up thereafter. (c) There is a need to calibrate our perioperative care standards and (d) enforce more consistent auditing in quality assurance. This project was conducted in a 1000-bed hospital serving eastern Singapore. INTERVENTION: We created an integrated anaesthesia consultant-led outreach service for hip fracture patients, based on a perioperative workflow system to provide proactive anaesthetist consults within 24 hours of admission in advance of surgical decision. This was streamlined with a coordinated follow-up system for preoptimisation until surgery. METHODS: Our quality improvement project applied the iterative Plan-Do-Study-Act model from pilot to sustainability stage. We collected data at baseline followed by 6-monthly audits from electronic databases.Primary outcomes measured were time to first anaesthesia consult and surgery. Secondary outcomes included rate of critical care reviews and admission, mortality rate, length of stay and time to nerve blocks. RESULTS: Post implementation, our service reviewed >600 hip fracture patients. Median time to anaesthesia consult reduced significantly from 35.3 hours (2019) to 21.5 hours (2021) (p=0.029). Median time to surgery was reduced from 61.5 hours (2019) to 50 hours (2021) (p=0.897) with a 13.6% increase in patients operated <48 hours. Critical care admissions, 6-monthly and 12-monthly mortality rates and time to nerve block were reduced with a greater percentage of patients discharged within 10 days. CONCLUSION: Our project focused on improving anaesthesia perioperative processes to address surgical delays in hip fracture patients. Our consultant-led anaesthesia service ensured that proactive anaesthesia care was delivered to provide sufficient time for preoptimisation with greater standardisation to follow-up, better communication and quality assurance.


Assuntos
Fraturas do Quadril , Bloqueio Nervoso , Consultores , Fraturas do Quadril/cirurgia , Humanos , Alta do Paciente , Melhoria de Qualidade
4.
Biomolecules ; 11(11)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34827581

RESUMO

Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV's stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.


Assuntos
Vibração , Fibras Musculares Esqueléticas , Mioblastos , Fosfatidilinositol 3-Quinases , Estatmina
6.
Int J Mol Sci ; 21(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003599

RESUMO

Discoidin domain receptor 1 (Drd1) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific Ddr1 knockout (OKOΔDdr1) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1f/f-4OHT mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1f/f-4OHT mice, OKOΔDdr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKOΔDdr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKOΔDdr1 mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1f/f-4OHT. Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. Ddr1 knockdown in osteoblasts resulted in decreased mineralization, ALP activity, phosphorylated p38 and protein levels of BMP2, Runx2, ALP, Col-I and OC during osteogenesis. Overexpression and knockdown of Ddr1 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/genética , Osteogênese/genética , Receptores de Dopamina D1/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Fosfatase Alcalina/genética , Animais , Proteína Morfogenética Óssea 2/genética , Colágeno/genética , Fêmur/crescimento & desenvolvimento , Fêmur/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , Camundongos Knockout , Osteoblastos/metabolismo , Fosforilação/genética
7.
Int J Mol Sci ; 21(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977456

RESUMO

We recently reported that the chondrocyte-specific knockout of discoidin domain receptors 1 (Ddr1) delayed endochondral ossification (EO) in the growth plate by reducing the chondrocyte hypertrophic terminal differentiation, and apoptosis. The biologic and phenotypic changes in chondrocytes in the articular cartilage with osteoarthritis (OA) are similar to the phenomena observed in the process of EO. Additionally, autophagy can promote chondrocyte survival and prevent articular cartilage from degradation in OA. On this basis, we explored the effect of Ddr1 inhibition on OA prevention and further investigated the roles of autophagy in treating OA with a Ddr1 inhibitor (7 rh). The anterior cruciate ligament transection (ACLT)-OA model was used to investigate the role of 7 rh in vivo. Forty 8-week-old mice were randomly assigned to four groups, including the sham group, ACLT group, and two treated groups (ACLT with 7 rh 6.9 nM or 13.8 nM). According to the study design, normal saline or 7 rh were intra-articular (IA) injected into studied knees 3 times per week for 2 weeks and then once per week for 4 weeks. The results showed that 7 rh treatment significantly improved the functional performances (the weight-bearing ability and the running endurance), decreased cartilage degradation, and also reduced the terminal differentiation markers (collagen type X, Indian hedgehog, and matrix metalloproteinase 13). Moreover, 7 rh decreased chondrocyte apoptosis by regulating chondrocyte autophagy through reducing the expression of the mammalian target of rapamycin and enhancing the light chain 3 and beclin-1 expression. These results demonstrated that the IA injection of 7 rh could reduce the chondrocyte apoptosis and promote chondrocyte autophagy, leading to the attenuation of cartilage degradation. Our observations suggested that the IA injection of 7 rh could represent a potential disease-modifying therapy to prevention OA progression.


Assuntos
Autofagia , Cartilagem Articular , Condrócitos , Receptor com Domínio Discoidina 1 , Osteoartrite , Animais , Antígenos de Diferenciação/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Diferenciação Celular , Linhagem Celular , Condrócitos/metabolismo , Condrócitos/patologia , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Receptor com Domínio Discoidina 1/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia
8.
FASEB J ; 34(4): 5767-5781, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32128899

RESUMO

Chondrocytes in growth plates are responsible for longitudinal growth in long bones during endochondral ossification. Discoidin domain receptor 1 (Ddr1) is expressed in chondrocytes, but the molecular mechanisms by which DDR1 regulates chondrocyte behaviors during the endochondral ossification process remain undefined. To elucidate Ddr1-mediate chondrocyte functions, we generated chondrocyte-specific Ddr1 knockout (CKOΔDdr1) mice in this study. The CKOΔDdr1 mice showed delayed development of the secondary ossification center and increased growth plate length in the hind limbs. In the tibial growth plate in CKOΔDdr1 mice, chondrocyte proliferation was reduced in the proliferation zone, and remarkable downregulation of Ihh, MMP13, and Col-X expression in chondrocytes resulted in decreased terminal differentiation in the hypertrophic zone. Furthermore, apoptotic chondrocytes were reduced in the growth plates of CKOΔDdr1 mice. We concluded that chondrocytes with Ddr1 knockout exhibit decreased proliferation, terminal differentiation, and apoptosis in growth plates, which delays endochondral ossification and results in short stature. We also demonstrated that Ddr1 regulates the Ihh/Gli1/Gli2/Col-X pathway to regulate chondrocyte terminal differentiation. These results indicate that Ddr1 is required for chondrocytes to regulate endochondral ossification in skeletal development.


Assuntos
Osso e Ossos/citologia , Diferenciação Celular , Condrócitos/citologia , Condrogênese , Receptor com Domínio Discoidina 1/fisiologia , Osteogênese , Animais , Condrócitos/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
Singapore Med J ; 60(3): 145-149, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30009316

RESUMO

INTRODUCTION: Adductor canal block (ACB) is hypothesised to provide superior analgesia to femoral nerve block (FNB) for total knee arthroplasty (TKA) while preserving quadriceps strength. METHODS: 30 patients undergoing TKA were randomised to receive either ACB or FNB. Baseline tests of quadriceps strength were performed. Ultrasound-guided blocks with 30 mL of 0.5% ropivacaine were administered before induction of general anaesthesia. Patient-controlled analgesia (morphine) was prescribed for postoperative analgesia. The primary outcome of this prospective, double-blinded, randomised controlled trial was morphine consumption (mean ± standard deviation) in the first 24 hours. Secondary outcomes were pain scores using a numeric rating scale (median and interquartile range [IQR]), quadriceps strength (% of baseline) and functional outcomes at 24 hours and 48 hours postoperatively. RESULTS: There was no statistically significant difference in morphine consumption at 24 hours between the ACB and FNB groups (21 ± 11 mg vs. 20 ± 12 mg; p = 0.85). No statistically significant differences were observed between the ACB and FNB groups in pain scores at 24 hours (at rest: 0 [IQR 0-2] vs. 0 [IQR 0-2]; on movement: 5 [IQR 4-8] vs. 5 [IQR 3-8]) and quadriceps strength (24 hours: 28.8% ± 26.1% vs. 26.8% ± 19.6% of baseline; 48 hours: 31.5 ± 23.1% vs. 33.7% ± 20.1% of baseline). There were also no statistically significant differences in functional outcomes and length of stay. CONCLUSION: We found no statistically significant differences in analgesic effects, quadriceps strength or functional recovery postoperatively between ACB and FNB.


Assuntos
Artroplastia do Joelho , Nervo Femoral , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Músculo Quadríceps/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia
10.
Singapore medical journal ; : 145-149, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-777549

RESUMO

INTRODUCTION@#Adductor canal block (ACB) is hypothesised to provide superior analgesia to femoral nerve block (FNB) for total knee arthroplasty (TKA) while preserving quadriceps strength.@*METHODS@#30 patients undergoing TKA were randomised to receive either ACB or FNB. Baseline tests of quadriceps strength were performed. Ultrasound-guided blocks with 30 mL of 0.5% ropivacaine were administered before induction of general anaesthesia. Patient-controlled analgesia (morphine) was prescribed for postoperative analgesia. The primary outcome of this prospective, double-blinded, randomised controlled trial was morphine consumption (mean ± standard deviation) in the first 24 hours. Secondary outcomes were pain scores using a numeric rating scale (median and interquartile range [IQR]), quadriceps strength (% of baseline) and functional outcomes at 24 hours and 48 hours postoperatively.@*RESULTS@#There was no statistically significant difference in morphine consumption at 24 hours between the ACB and FNB groups (21 ± 11 mg vs. 20 ± 12 mg; p = 0.85). No statistically significant differences were observed between the ACB and FNB groups in pain scores at 24 hours (at rest: 0 [IQR 0-2] vs. 0 [IQR 0-2]; on movement: 5 [IQR 4-8] vs. 5 [IQR 3-8]) and quadriceps strength (24 hours: 28.8% ± 26.1% vs. 26.8% ± 19.6% of baseline; 48 hours: 31.5 ± 23.1% vs. 33.7% ± 20.1% of baseline). There were also no statistically significant differences in functional outcomes and length of stay.@*CONCLUSION@#We found no statistically significant differences in analgesic effects, quadriceps strength or functional recovery postoperatively between ACB and FNB.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Analgesia Controlada pelo Paciente , Métodos , Analgésicos Opioides , Usos Terapêuticos , Anestésicos Locais , Artroplastia do Joelho , Método Duplo-Cego , Nervo Femoral , Morfina , Usos Terapêuticos , Bloqueio Nervoso , Métodos , Manejo da Dor , Métodos , Medição da Dor , Dor Pós-Operatória , Tratamento Farmacológico , Estudos Prospectivos , Músculo Quadríceps , Resultado do Tratamento , Ultrassonografia
11.
Chinese Pharmacological Bulletin ; (12): 550-556, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-705083

RESUMO

Aim To study the effects of L-borneol on the chloride channel and cell volume of human umbili-cal vein endothelial cells (HUVECs). Methods Whole-cell patch-clamp technique was used to record chloride currents. The expression of ClC-3 protein was down-regulated by siRNA interference technique. The cell volume was measured by dynamic image analysis. Results 20 nmol·L-1L-borneol significantly activa-ted chloride current in HUVEC (79.59 ± 4.90) pA/pF, which could be inhibited by chloride channel blockers,NPPB and DIDS. The outward current inhib-itory rate of NPPB was (95.57 ± 2.57)%, while that of DIDS was (97.28 ± 6.36)%. The chloride current activated by L-borneol significantly decreased after the silence of ClC-3 (27.03 ± 3.89) pA/pF. Cell volume was markedly reduced by L-borneol (14.38 ± 1.58)%,which was inhibited after NPPB appliance. Conclusion L-borneol can activate ClC-3 chloride channel in HUVECs, which induces Cl- outflow then cell volume decrease.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-701123

RESUMO

AIM:To study the effect of ClC-3 gene over-expression on thyroid structure and function in mice. METHODS:Three-months-old FVB mice were used to study the difference of thyroid structure and function between wild-type(WT)mouse and ClC-3 transgene mice.The expression and distribution of ClC-3 in the thyroid of mice were deter-mined by the methods of qPCR,Western blot and immunofluorescence.Behavioral monitoring was performed on the daily activities of mice.Serum concentrations of total triiodothyronine(TT3), total thyroxine(TT4)and thyrotropin(TSH) were measured by ELISA.RESULTS:Compared with the WT group,the expression of ClC-3 in the thyroid of ClC-3 trans-gene group was significantly increased(P<0.05).The thyroid gland showed obvious hyperplasia and the folliculi glandu-lae thyreoideae was significantly bigger in ClC-3 transgene mice(P<0.05).The weight loss was increased in ClC-3 trans-gene mice(P<0.05).The expression of TT3 and TT4 were significantly higher than that of WT group(P<0.05),but the change of TSH was not obvious.CONCLUSION:ClC-3 over-expression results in thyroid hyperplasia and thyroid hor-mone secretion.This study suggests that ClC-3 is likely to be involved in the synthesis of thyroid hormones.

13.
Int J Mol Sci ; 18(11)2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29140298

RESUMO

The natural pure compound obtusilactone A (OA) was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP) activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.


Assuntos
Células da Medula Óssea/citologia , Lignanas/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Cinnamomum/química , Regulação da Expressão Gênica/efeitos dos fármacos , Imageamento Tridimensional , Lignanas/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos BALB C , Osseointegração/efeitos dos fármacos , Osseointegração/genética , Osteogênese/genética , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Tíbia/crescimento & desenvolvimento , Microtomografia por Raio-X
14.
J Nutr Biochem ; 43: 132-140, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28285155

RESUMO

Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks. Western blotting was performed to measure the expression/phosphorylation levels of several cortical and hippocampal proteins, including amyloid precursor protein (APP), tau, phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), receptor for advanced glycation end products (RAGEs), erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF). Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet. Thus, grape powder consumption produced beneficial effects in HFHF-diet-fed rats, exhibiting the potential to ameliorate changes in neurodegeneration-related proteins in the brain.


Assuntos
Encéfalo/metabolismo , Hiperglicemia/fisiopatologia , Vitis/química , Animais , Peso Corporal , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtornos Cognitivos/dietoterapia , Transtornos Cognitivos/etiologia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Frutose/efeitos adversos , Hiperglicemia/dietoterapia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Doenças Neurodegenerativas/metabolismo , Pós/farmacologia , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteínas tau/metabolismo
15.
Clin Immunol ; 175: 34-40, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27876461

RESUMO

The CXCL5 chemokine is important for neutrophil accumulation in tumour tissues. In this report, we attempted to clarify whether and how infiltrating tumour-associated neutrophils (TANs) in laryngeal squamous cell carcinoma (LSCC) affect the proliferation and activation of T cells. We examined chemokine expression by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and performed an immunohistochemical analysis of LSCC microarrays. The relationship between CXCL5 and CD66b (a neutrophil marker) was investigated by immunofluorescence staining. We found that CXCL5 was upregulated in LSCC tissues, whereas CXCL5 levels were decreased in LSCC patient serum. Furthermore, high levels of CXCL5 were significantly correlated with intratumoural neutrophil infiltration. Compared with peripheral blood neutrophils (PBNs), TANs significantly inhibited T cell proliferation and decreased IFN-γ and TNF-α secretion. These data suggest that excessive neutrophil infiltration is associated with advanced clinical stages of LSCC (T3 or T4, III or IV, and N1 or N2).


Assuntos
Carcinoma de Células Escamosas/imunologia , Quimiocina CXCL5/metabolismo , Neoplasias Laríngeas/imunologia , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células/fisiologia , Quimiocina CXCL5/sangue , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/imunologia
16.
Gastroenterol Res Pract ; 2016: 5789232, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27651791

RESUMO

It has been indicated that probiotics can be nourished by consuming prebiotics in order to function more efficiently, allowing the bacteria to stay within a healthy balance. In this study, we investigated the effects of xylooligosaccharides- (XOS-) enriched rice porridge consumption on the ecosystem in the intestinal tract of human subjects. Twenty healthy subjects participated in this 6-week trial, in which 10 subjects received XOS-enriched rice porridge while the others received placebo rice porridge. Fecal samples were collected at the end of weeks 0, 1, 3, 4, 6, and 7 for microorganism examination. The results showed that 6-week daily ingestion of the XOS-enriched rice porridge induced significant increases in fecal bacterial counts of Lactobacillus spp. and Bifidobacterium spp., as well as decreases in Clostridium perfringens without changing the total anaerobic bacterial counts, compared to that of placebo rice porridge. However, fluctuations in the counts of coliforms were observed in both groups during the 6-week intervention. In conclusion, the intestinal microbiota balance was improved after daily consumption of 150 g of rice porridge containing XOS for 6 weeks, demonstrating the prebiotic potential of XOS incorporated into foods. This also indicates the effectiveness of XOS as a functional ingredient in relation to its role as a prebiotic compound.

17.
J Nutr Biochem ; 34: 52-60, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27206221

RESUMO

Research has suggested that the consumption of foods rich in polyphenols is beneficial to the cognitive functions of the elderly. We investigated the effects of grape consumption on spatial learning, memory performance and neurodegeneration-related protein expression in aged rats fed a high-fructose-high-fat (HFHF) diet. Six-week-old Wistar rats were fed an HFHF diet to 66 weeks of age to establish a model of an HFHF dietary pattern, before receiving intervention diets containing different amounts of grape powder for another 12 weeks in the second part of the experiment. Spatial learning, memory performance and cortical and hippocampal protein expression levels were assessed. After consuming the HFHF diet for a year, results showed that the rats fed a high grape powder-containing diet had significantly better spatial learning and memory performance, lower expression of ß-amyloid and ß-secretase and higher expression of α-secretase than the rats fed a low grape powder-containing diet. Therefore, long-term consumption of an HFHF diet caused a decline in cognitive functions and increased the risk factors for neurodegeneration, which could subsequently be ameliorated by the consumption of a polyphenol-rich diet.


Assuntos
Envelhecimento , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/metabolismo , Nootrópicos/uso terapêutico , Vitis/química , Animais , Comportamento Animal , Córtex Cerebral/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Liofilização , Frutose/efeitos adversos , Frutas/química , Hipocampo/metabolismo , Masculino , Proteínas do Tecido Nervoso/genética , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Neurônios/metabolismo , Nootrópicos/análise , Nootrópicos/química , Polifenóis/análise , Polifenóis/uso terapêutico , Ratos Wistar , Aprendizagem Espacial
18.
Acta Otolaryngol ; 136(8): 826-33, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27080151

RESUMO

CONCLUSION: Improved prognosis associated with HPV-positive status may depend on lower CD4/CD8 ratio. Th1 CD4(+ )T cells were found to be the major sub-set of T lymphocytes in the HPV positive laryngeal squamous cell carcinoma microenvironment. BACKGROUND: To examine the prognostic significance of human papillomavirus (HPV) status in relation to the ratio of CD4/CD8 in LSCC. METHODS: In this study, 46 LSCC biopsy samples were retrospectively assessed using immunohistochemistry for CD4(+ )and CD8(+ )tumor infiltrating lymphocytes (TILs). HPV status was determined by HPV in situ hybridization (ISH) and p16(INK4A) immunohistochemistry. Of the 46 samples, 21 were evaluated for the expression of IFN-γ and IL-4 by quantitative real-time PCR (qRT-PCR). The influence of HPV status on locoregional tumor control and T-cell sub-sets infiltrating tumor microenvironment were investigated. RESULTS: Nineteen patients (41.3%) were classified as HPV positive, who had improved disease-free survival (28% in reduction, hazard ratio =0.10; 95% CI =0.011-0.938). A direct correlation between the HPV status and the ratio of CD4/CD8 or mean levels of CD8(+ )T cells was observed. Compared with the HPV-negative samples, HPV-positive samples had a higher ratio of IFN-γ/IL-4 (24.43 ± 29.89 vs 3.90 ± 4.03; p = 0.0375).


Assuntos
Relação CD4-CD8 , Carcinoma de Células Escamosas/imunologia , Neoplasias Laríngeas/imunologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Genes p53 , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/virologia , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Estudos Retrospectivos , Equilíbrio Th1-Th2
19.
Cell Biol Int ; 36(9): 833-41, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22582758

RESUMO

LPA (lysophosphatidic acid) is a natural phospholipid that plays important roles in promoting cancer cell proliferation, invasion and metastases. We previously reported that LPA induces ovarian cancer cell dispersal and disruption of AJ (adherens junction) through the activation of SFK (Src family kinases). In this study, we have investigated the regulatory mechanisms during the early phase of LPA-induced cell dispersal. An in vitro model of the ovarian cancer cell line SKOV3 for cell dispersal was used. LPA induces rapid AJ disruption by increasing the internalization of N-cadherin-ß-catenin. By using immunoprecipitations, LPA was shown to induce increased tyrosine phosphorylation of ß-catenin and alter the balance of ß-catenin-bound SFK and PTP1B (phosphotyrosine phosphatase 1B). The altered balance of tyrosine kinase/phosphatase correlated with a concomitant disintegration of the ß-catenin-α-catenin, but not the ß-catenin-N-cadherin complex. This disintegration of ß-catenin from α-catenin and the cell dispersal caused by LPA can be rescued by blocking SFK activity with the chemical inhibitor, PP2. More importantly, PP2 also restores the level of PTP1B bound to ß-catenin. We propose that LPA signalling alters AJ stability by changing the dynamics of tyrosine kinase/phosphatase bound to AJ proteins. This work provides further understanding of the early signalling events regulating ovarian cancer cell dispersal and AJ disruption induced by LPA.


Assuntos
Junções Aderentes/metabolismo , Caderinas/metabolismo , Cateninas/metabolismo , Lisofosfolipídeos/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Complexos Multiproteicos/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Ovarianas , Fosforilação , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
20.
Waste Manag Res ; 28(1): 29-35, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19710121

RESUMO

In this study, the use of crumb tyres as additives to concrete was investigated. For some time, researchers have been studying the physical properties of concrete to determine why the inclusion of rubber particles causes the concrete to degrade. Several methods have been developed to improve the bonding between rubber particles and cement hydration products (C-S-H) with the hope of creating a product with an improvement in mechanical strength. In this study, the crumb tyres were treated with waste organic sulfur compounds from a petroleum refining factory in order to modify their surface properties. Organic sulfur compounds with amphiphilic properties can enhance the hydrophilic properties of the rubber and increase the intermolecular interaction forces between rubber and C-S-H. In the present study, a colloid probe of C-S-H was prepared to measure these intermolecular interaction forces by utilizing an atomic force microscope. Experimental results showed that rubber particles treated with waste organic sulfur compounds became more hydrophilic. In addition, the intermolecular interaction forces increased with the adsorption of waste organic sulfur compounds on the surface of the rubber particles. The compressive, tensile and flexural strengths of concrete samples that included rubber particles treated with organic sulfur compound also increased significantly.


Assuntos
Conservação dos Recursos Naturais/métodos , Materiais de Construção/análise , Resíduos Industriais , Borracha/química , Compostos de Enxofre/química , Força Compressiva , Microscopia de Força Atômica , Maleabilidade , Resistência à Tração
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