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Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.
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Neoplasias Pulmonares , Esferoides Celulares , Humanos , Células Tumorais Cultivadas , Células Endoteliais/patologia , Neoplasias Pulmonares/patologia , Pulmão/patologiaRESUMO
Light-curing resin cements, each comprising one of five different inorganic fillers (non-porous and porous spherical SiO2 particles, irregularly shaped glass and ZrO2 particles, and porous ZrO2 spheres), monomers, and polymerization initiators were prepared to determine the effect of filler morphology on the adhesive strength of the resin cement. The strength of adhesion to a computer-aided design/computer-aided manufacturing (CAD/CAM) resin block was investigated mechanically by measuring the tensile bond strength, flexural strength, and elastic modulus. The resin cement containing sub-micron porous ZrO2 spheres had significantly higher tensile bond strength than the other resin cements. The resin cement containing the porous ZrO2 spheres had markedly lower flexural strength and elastic modulus values than the resin cements containing SiO2 and glass fillers.
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Colagem Dentária , Cimentos de Resina , Cimentos de Resina/química , Dióxido de Silício , Propriedades de Superfície , Teste de Materiais , Resistência à TraçãoRESUMO
BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.
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Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Biomarcadores , Humanos , Inflamação/complicações , AVC Isquêmico/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
With the advantages of low cost, universal applicability, and in situ detection, the conic invariant of the tested aperture diameter was obtained by ellipse geometric fitting on the aperture surface. The world coordinate system was established, and the transformation relationship between the world coordinate system and the camera coordinate system was obtained by the calibration. The improved Candy algorithm and coordinate transformation relationship could be used to project the sub-pixel coordinates of the aperture edge onto the aperture surface. Then, the ellipse geometric fitting was performed on the aperture edge curve surface to obtain the conic invariant. Finally, the conic invariant was used to measure the aperture diameter on the test bench.
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Porous ceria was obtained using a unique solvothermal reaction in acetonitrile, applying high temperature and pressure. The resulting material comprised homogeneous and monodisperse spheres and exhibited an extremely large surface area of 152 m2 g-1. From catalytic performance evaluation by vapor- and liquid-phase reactions, the synthesized porous ceria showed superior and different reaction activity compared with commercial CeO2. To examine the origin of the reaction activity of the present porous ceria, synchrotron hard X-ray photoelectron spectroscopy (HAXPES) measurements were carried out. The systematic study of HAXPES measurements revealed that the obtained porous ceria with the present solvothermal method contained a very high concentration of Ce3+. Moreover, O2-pulse adsorption analyses demonstrated a significant oxygen adsorption capacity exceeding 268 µmol-O g-1 at 400 °C owing to its high contents of Ce3+ species.
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This study demonstrates the applications of Bacillus coagulans in alcohol elimination. Bacillus coagulans has recently drawn tremendous interest in the food industry and medicine considering its great environmental tolerance and beneficial effects on improving gastrointestinal diseases. However, few scientific reports connect its utilities with alcohol elimination. In this study, we introduced the unique strain B. coagulans TCI711 for such exploration. TCI711 contained alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) by mass spectrum and resisted gastric acid and bile acid. Also, taking TCI711 capsules for a week can significantly improve alcohol metabolism in humans (breath alcohol level indicated 0 mg/kg in 2 h after drinking 75 mL of whisky). In brief, this exploratory research unveiled the potent applications of B. coagulans in alcohol elimination in humans.
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Bacillus coagulans , Etanol/metabolismo , Probióticos , Bacillus coagulans/metabolismo , Ácidos e Sais Biliares , HumanosRESUMO
This research unveils the synergistic effect of brown sugar, longan, ginger, and jujube on the beneficial effects of antioxidation and anti-inflammation. Longan, ginger, and jujube are ubiquitous herbs in traditional Chinese medicine (TCM) and are frequently used in folk remedies. Longan and ginger have been reported to be beneficial for antioxidation, anti-inflammation, ant-obesity, and nonalcoholic fatty liver disease (NAFLD) improvements. However, the potential scientific and medical benefits of their combination Brown Sugar Longan Ginger Tea (BSLGT), a popular drink in Chinese cultures, are elusive. Through the in vitro methodologies, we discovered that BSLGT could significantly improve the mitochondrial activity, antioxidant capacity, lipid content, and inflammatory response in human hepatocytes. In addition, BSLGT also exerted positive effects on the downregulation of atherosclerosis-associated, vasoconstrictor, and thrombosis-related gene expression in human umbilical vein endothelial cells. In short, our experimental results successfully revealed that the antioxidative and anti-inflammatory effects of BSLGT may have the potential to improve liver metabolism and cardiovascular inflammation although solid evidence requires further investigation.
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We explored the psychological changes in suspected patients during the coronavirus disease 2019 (COVID-19) epidemic and obtained evidence for early psychological guidance and intervention in this group. A total of 31 inpatients with suspected COVID-19 were identified at our hospital. The depression module of the Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder (GAD)-7 scale, and the Self-Reporting Questionnaire (SRQ-20) mental health self-assessment questionnaire were used to assess depression, anxiety, and overall mental health. Among the patients, 32.3% had symptoms of depression and 19.4% had symptoms of anxiety. Levels of anxiety and fear varied. In comparing the PHQ-9 and 7-item Generalized Anxiety Disorder Scale scores of suspected and confirmed patients, there was no significant difference in the distribution of severity of anxiety or depression in the 2 groups. The PHQ-9 scores indicated mild depression symptoms in 25.8% of suspected patients, moderate symptoms in 0%, and severe symptoms in 6.5%. Overall, 50% of confirmed patients had symptoms, with 30.8% classified as mild, 15.4% classified as moderate, and 3.8% classified as severe. The 7-item Generalized Anxiety Disorder Scale scores in the group of suspected patients showed that 9.7% had mild symptoms, 0% had moderate symptoms, and 9.7% had severe symptoms. In the group of confirmed patients, 38.4% had symptoms (34.6% mild, 0% moderate, and 3.8% severe). Diagnosed patients had more visible symptoms of depression and different total PHQ-9 scores. During the COVID-19 epidemic, suspected and diagnosed patients had different levels of mental health problems. Diagnosed patients had more visible symptoms. The performance of suspected patients was higher, but their mental state was more polarized. It may thus be important to monitor the psychological state of suspected patients as early as possible to enable timely interventions that promote psychological rehabilitation.
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Ansiedade/diagnóstico , Betacoronavirus , Infecções por Coronavirus/psicologia , Depressão/diagnóstico , Pneumonia Viral/psicologia , Adulto , Idoso , Ansiedade/epidemiologia , Ansiedade/virologia , COVID-19 , China/epidemiologia , Infecções por Coronavirus/virologia , Depressão/epidemiologia , Depressão/virologia , Medo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Escalas de Graduação Psiquiátrica , SARS-CoV-2 , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
This work unveils a fish collagen drink for improvement of skin aging. Previous studies frequently discussed the skin aging from the angle of the representative characteristics of collagen loss and the oxidative-induced expression of proteolytic enzymes matrix metalloproteinases (MMPs), but few groups comprehensively investigated the efficacy of oral hydrolyzed collagen for enhancing protein folding and DNA repair as well as improving notable cell behaviors. To delineate the broad perspective on delaying skin aging, we inspected the collagen drink-treated fibroblast cells from the molecular and cellular aspects. The results show that the collagen drink could perform the compact antiaging effects on ROS inhibition, the facilitation of the synthesis of extracellular matrix (ECM) proteins, the increase of mitochondrial activity, and improvement of the gene expression regarding correct protein folding, DNA mismatch repair (MMR) and base excision repair (BER). Although the experimental results are built on the cellular models, we believe that the positive outcomes can provide more details on the influence of oral hydrolyzed collagen supplement for antiaging. In short, we have successfully proved that the synergistic effect of the collagen drink could not only reduce the oxidative damage but also ameliorate the cell functionality to compensate the harmful effects induced by UVA.
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Antioxidantes/farmacologia , Bebidas , Senescência Celular/efeitos dos fármacos , Colágeno/administração & dosagem , Colágeno/biossíntese , Reparo do DNA , Fibroblastos/metabolismo , Dobramento de Proteína , Administração Oral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Senescência Celular/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Elastina/biossíntese , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Dobramento de Proteína/efeitos dos fármacos , Dobramento de Proteína/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Raios UltravioletaRESUMO
A characteristic effect of a nano-concave-convex structure of a zirconia nanoparticle assembly with an inherent porous structure and huge surface area enabled us to introduce systematic surface modification by thermal treatment to smooth surface and polymer impregnation to mask the nano-concave-convex structure of the zirconia nanoparticle assembly. A polymer composite prepared from 30 wt% poly(N-isopropylacrylamide) containing 0.02 wt% zirconia nanoparticle assembly with the inherent nano-concave-convex surface structure showed the highest tensile strength in mechanical tensile testing. However, both sintered zirconia nanoparticle assembly with smooth surface and zirconia nanoparticle assemblies with polymer masked surface showed lower strength with longer elongation at break in mechanical tensile testing.
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Submicron-sized niobia (Nb2O5) porous spheres with a high specific surface area (300 m2 g-1) and nano concave-convex surfaces were synthesized via a rapid one-pot single-step alcothermal reaction. Prolonged reaction time or high reaction temperatures resulted in a morphology change of Nb2O5 from amorphous sphere to rod crystals with hexagonal crystal phase. A similar alcothermal reaction yielded TiO2-Nb2O5 composite porous spheres, whose Ti : Nb molar ratio was controlled by changing the precursor solution component ratios. A simple thermal treatment of amorphous TiO2-Nb2O5 porous spheres consisting of 1 : 2 (molar ratio) Ti : Nb at 600 °C for 2 h induced crystal phase transfer from amorphous to a monoclinic crystal phase of submicron-sized TiNb2O7 porous spheres with a specific surface area of 50 m2 g-1.
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Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.
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AIM: To investigate the association between structured self-monitoring of blood glucose (SMBG) and diabetes self-efficacy in Chinese patients. METHODS: This study was a single-centre, open-label, prospective, randomized controlled trial. A total of 250 type 1 and type 2 diabetes patients were recruited and randomly assigned to the structured SMBG group and the control group in a 1:1 ratio. The main outcome observed in this subgroup analysis was a change in the diabetes self-efficacy scale (DSES) scores. A multivariate generalized estimating equation was used to evaluate factors affecting the DSES scores. RESULTS: We found that the DSES scores tended to decrease significantly with the follow-up time in the intervention group (Wald ß = 7.882, P < .001; Wald ß = 3.130, P = .003; Wald ß = 7.879, P < .001). However, no significant differences in the DSES scores were detected in the control group. Glycaemic control improved in both the intervention and control groups at the third month (P < .05). In the intervention group, sustained improvement of the DSES scores maintained the improvement in glycaemic control through the sixth month. In the control group, glycaemic control tended to deteriorate in the sixth month without the support of an improved DSES scores (P = .056). CONCLUSION: Structured SMBG could contribute to the effective and persistent improvement of diabetes self-efficacy. (ClinicalTrials.gov, NCT02225691).
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Automonitorização da Glicemia/psicologia , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Autoeficácia , Idoso , Glicemia , China , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND/AIMS: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. METHODS: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. RESULTS: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-ß expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. CONCLUSIONS: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.
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Síndrome Cardiorrenal/patologia , Estresse do Retículo Endoplasmático/fisiologia , Coração/fisiopatologia , Rim/patologia , Sirtuína 1/metabolismo , Animais , Síndrome Cardiorrenal/etiologia , Síndrome Cardiorrenal/metabolismo , Creatinina/sangue , Desmina/metabolismo , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Rim/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Miocárdio/patologia , Nefrectomia , Sirtuína 1/deficiência , Sirtuína 1/genética , Fator de Transcrição CHOP/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: The rate of glycemic control among diabetes patients in China is currently low. The current study aims at determining the effect of structured self-monitoring of blood glucose (SMBG) on blood glucose control as well as quality of life (QoL) in Chinese diabetes patients. METHODS: In a 24-week, single-center, randomized, open-label, prospective trial, patients with glycated hemoglobin A1c (HbA1c) >8.0% were randomized to an intervention group for structured SMBG (n = 121) or a control group (n = 129). Patient data were analyzed separately according to treatment with or without insulin. At 0, 3rd, and 6th months, life satisfaction was assessed using the Chinese Normal Audit of Diabetes-Dependent Quality of Life (CN-ADDQoL) questionnaire. RESULTS: The mean HbA1c decrease from baseline to the study end was significant for both groups with insulin treatment (intervention group: -1.79% ± 1.97%, P < 0.001; control group: -1.05% ± 1.87%, P < 0.001) or without insulin treatment (intervention group: -1.91% ± 1.90%, P < 0.001; control group: -1.35% ± 1.82%, P < 0.001). Moreover, the insulin-treated patients in the intervention group showed a significantly more robust HbA1c decrease than those in the control group (P = 0.007). Both therapeutic subgroups in the intervention group had a significantly higher frequency of SMBG than those in the control group (P < 0.001), but no strict deterioration of the QoL was detected. In addition, a significant HbA1c reduction after 6 months of SMBG was seen for both insulin-treated patients (P = 0.027) and noninsulin-treated patients (P = 0.006) younger than 66 years. CONCLUSIONS: Featured with no strict deterioration of QoL, structured SMBG was proven to be effective on the glycemic control in patients with insulin treatment, as well as in young and middle-aged patients without insulin treatment.
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Automonitorização da Glicemia , Glicemia/análise , Diabetes Mellitus/psicologia , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Complexo I de Transporte de Elétrons/metabolismo , Insulina/administração & dosagem , Mitocôndrias Cardíacas/patologia , Chaperonas Moleculares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Células HeLa , Humanos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Regulação para Cima/efeitos dos fármacosRESUMO
In regenerative medicine, it has become increasingly important to collect cultured tissues using non-invasive methods. Enzymatic deadhesion is normally used to collect cells, but this method cannot be used when trying to collect whole tissues in order to avoid damaging cell-cell interactions. In order to resolve this issue, a thermoresponsive culture dish with poly(N-isopropyl acrylamide) (PNIPAAm) has been employed. This system can change its hydrophobicity depending on temperature. Thus, tissues can attach above 37 °C and be detached below 20 °C. However, the PNIPAAm system has some issues related to cost and detachment time. In this study, we developed a novel thermoresponsive detachment system using a polysaccharide derivative. We chose hydroxy butyl chitosan (HBC) as the thermoresponsive polymer because of its high biocompatibility and rapid phase transition. We developed a novel method of HBC synthesis in conditions that were milder than previously reported. We used spin-coating to make a thin coating on two kinds of culture dishes with various concentrations of HBC solution. Seeded cells attached to the surface at less than 0.5 mg/ml HBC coating concentration, and they could be successfully detached by simply lowering the temperature of the suspension dishes without enzymatic treatment; the cells took only 5-20 min to detach. To evaluate this system, we measured three metrics related to cell culturing on culture dishes: initial attachment rate, detachment rate and tissue detachment time. The study revealed that tissues could be detached faster on the suspension dishes used in this study than on PNIPAAm grafted dishes when HBC was coated at 0.5 mg/ml. We successfully developed a novel tissue detachment system using HBC. These results suggest that smart polymers may be useful in regenerative medicine.
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Adesão Celular/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Transição de Fase , Temperatura , Resinas Acrílicas/química , Proliferação de Células/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Fatores de TempoRESUMO
Hydrogel preparations using poly(N-vinylformamide) (PNVF) and poly(N-vinylacetamide) (PNVA), which are composed of non-conjugated vinyl monomers, N-vinylformamide (NVF) and N-vinylacetamide (NVA), were investigated without chemical crosslinkers. Hydrogen bonding interaction between the polymers and poly(ethylene glycol) have been firstly attempted to result in unstable film, which is easily soluble in water. On the other hand, the simple thermal treatment of the PNVF films at 200 °C for several hours produced the hydrogels after water immersion, although PNVA did not produce any hydrogels under the same condition. The swelling ratios of the formed hydrogel ranged from 100 to 250. The analysis of the supernatant reveals the structural change at alpha proton of PNVF. Furthermore, the decrease of molecular weights were observed by SEC analysis when the hydrogels formed. The possible mechanism of the crosslinking reaction is also discussed. The present study provides the novel method to prepare PNVF hydrogels without the use of chemical crosslinkers.
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The stereocomplex formation of poly(l,l-lactide) (PLLA) and poly(d,d-lactide) (PDLA) was selected in order to investigate the interaction of the two surfaces including hydrogen bonding and van der Waals interaction. Adhesion force measurement using surface force apparatus (SFA) equipped with an optical microscope was conducted on the PLLA and PDLA spin-coated films. The adhesion forces, Fad, phenomenologically followed the linear relation with the applied normal load, L. For the force Fad between PLLA and PDLA films with low molecular weights (PLLA, Mn = 2800; PDLA, : Mn = 2100), the slope of linear fitting of Fad vs L was significantly larger for the heterointerface (PLLA/PLDA) compared with that for the homointerface (PLLA/PLLA and PDLA/PDLA). However, when polymers with higher molecular weights (PLLA, Mn = 8500; PDLA, Mn = 8300) were measured, the slopes of linear fitting lines were almost the same for hetero- and homointerfaces. This indicated that the mobility of the lower molecular weight PLLA/PDLA films promoted the selective interaction of PLLA and PDLA under the applied normal loads. The adhesion between the outermost PLLA layer and PDLA layer prepared by layer-by-layer (LbL) assembly was also measured. It is interesting that the adhesion force was very weak in this case. This weak adhesion could be explained by the much less mobility of the polymer chain due to the stereocomplex formation within the LbL layers. This study demonstrated that the adhesion force due to the selective interaction of PLLA and PDLA between PLLA/PDLA films could be directly measured, and depended on the mobility of the outermost polymer chains, which reflected the different structures of polymer chains in the organized complex films.
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Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKß phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKß phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury.