RESUMO
This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.
Assuntos
Biomarcadores , Ácidos Graxos não Esterificados , Lipidômica , Metabolômica , Humanos , Feminino , Masculino , Adulto , Ácidos Graxos não Esterificados/sangue , Lipidômica/métodos , Pessoa de Meia-Idade , Metabolômica/métodos , Biomarcadores/sangue , Cromatografia Gasosa-Espectrometria de Massas , Ceratoconjuntivite/sangue , Ceratoconjuntivite/diagnóstico , Ensaio de Imunoadsorção Enzimática , Espectrometria de Massas em Tandem , Fosfolipases A2 do Grupo II/sangueRESUMO
Expression of Concern for 'Surface modification of intraocular lenses via photodynamic coating for safe and effective PCO prevention' by Junmei Tang et al., J. Mater. Chem. B, 2021, 9, 1546-1556, https://doi.org/10.1039/D0TB02802A.
RESUMO
OBJECTIVES: Cognitive impairment in cerebral small vessel disease (CSVD) is a common cause of vascular dementia and is often accompanied by mental disorders. The purpose of this study was to investigate the effect of continuous theta burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on the cognitive function and Hamilton depression (HAMD) scores in patients with CSVD. METHODS: A total of 30 CSVD patients who met the inclusion criteria were randomly assigned to either the sham or cTBS group. The patients in both groups received routine cognitive function training. All the patients were under treatment for 14 sessions, with one session per day (each cTBS conditioning session consisted of three-pulse bursts at 50 Hz repeated at 5 Hz, 80% MT, and 600 pulses). Before and after the treatment, the patients in both groups were evaluated using the Montreal Cognitive Assessment (MoCA), Stroop Color-Word Test (SCWT), Trail Marking Test (TMT), Digital Span Test (DST), and HAMD test. The time to complete the SCWT and TMT were recorded. The scores of the MoCA, DST and HAMD test were recorded. RESULTS: The HAMD scores in the cTBS group decreased significantly compared to the control (p < 0.05). There were no significant differences in the MoCA (including the MoCA subitems) or DST scores or in the SCWT or TMT completion times between the two groups (p > 0.05). For the HAMD scores and the MoCA subitem visuospatial/executive scores, the SCWT-B and SCWT-C completion times in the two groups both improved significantly before and after treatment (p < 0.05). For the MoCA scores, the DST-backward scores and the TMT-B completion times in the cTBS group improved significantly before and after treatment (p < 0.05). There was no significant difference in the SCWT-A, TMT-A completion times and MoCA subitems naming, attention, language, abstraction, delayed recall, and orientation scores either before or after treatment in the two groups or between the two groups (p > 0.05). CONCLUSIONS: In this study, cTBS over the right DLPFC decreased the HAMD scores significantly in patients with CSVD but had no significant improvement or impairment effects on cognitive function. cTBS over the right DLPFC could be used to treat CSVD patients with depression symptoms.
RESUMO
BACKGROUND: Dihydroartemisinin (DHA), a natural agent, exhibits potent anticancer activity. However, its biological activity on prostate cancer (PCa) 22Rv1 cells has not been previously investigated. OBJECTIVE: In this study, we demonstrate that DHA induces anticancer effects through the induction of apoptosis and autophagy. METHODS: Cell viability and proliferation rate were assessed using the CCK-8 assay and cell clone formation assay. The generation of reactive oxygen species (ROS) was detected by flow cytometry. The molecular mechanism of DHA-induced apoptosis and autophagy was examined using Western blot and RT-qPCR. The formation of autophagosomes and the changes in autophagy flux were observed using transmission electron microscopy (TEM) and confocal microscopy. The effect of DHA combined with Chloroquine (CQ) was assessed using the EdU assay and flow cytometry. The expressions of ROS/AMPK/mTOR-related proteins were detected using Western blot. The interaction between Beclin-1 and Bcl-2 was examined using Co-IP. RESULTS: DHA inhibited 22Rv1 cell proliferation and induced apoptosis. DHA exerted its anti-prostate cancer effects by increasing ROS levels. DHA promoted autophagy progression in 22Rv1 cells. Inhibition of autophagy enhanced the pro-apoptotic effect of DHA. DHA-induced autophagy initiation depended on the ROS/AMPK/mTOR pathway. After DHA treatment, the impact of Beclin-1 on Bcl-2 was weakened, and its binding with Vps34 was enhanced. CONCLUSION: DHA induces apoptosis and autophagy in 22Rv1 cells. The underlying mechanism may involve the regulation of ROS/AMPK/mTOR signaling pathways and the interaction between Beclin-1 and Bcl-2 proteins. Additionally, the combination of DHA and CQ may enhance the efficacy of DHA in inhibiting tumor cell activity.
RESUMO
Objective: To analyze the correlation between balance function and gait parameters of patients with basal ganglia infarction. And to observe the influence of balance function on plantar pressure and hemiplegia gait based on the Berg Balance Scale (BBS) score. Methods: One hundred and forty patients with cerebral infarction hemiplegia in the basal ganglia region (a study group, n = 140) and healthy people (a control group, n = 140) were enrolled. The study group was evaluated with the BBS, the 10 m walking test (10MWT), and the timed up-and-go test (TUGT). The gait parameters and the peak plantar pressure were measured in both groups while walking, and the differences between the groups were compared. In addition, the characteristics of the plantar pressure curve of the hemiplegic and non-hemiplegic sides during walking and the correlation between the 10MWT, the TUGT, the plantar pressure peak, the gait parameters,and the BBS score were analyzed in the study group. Results: The peak plantar pressure of the forefoot and heel, stride length, lateral symmetry, stand phase, swing phase, and dual stand phase of both sides in the study group were significantly lower than those in the control group (P < 0.05). The BBS score negatively correlated with the 10MWT, the TUGT, the peak plantar pressure of the hemiplegic forefoot, midfoot, and the non-hemiplegic midfoot, the anterior to posterior position (ant/post position), hemiplegic stand phase, and the dual stand phase (P < 0.05). The BBS score positively correlated with the hemiplegic swing phase and stride length (P < 0.05). Conclusion: A correlation was found between the forefoot plantar pressure and the stand phase of the hemiplegic limbs, the ant/post position, and the balance function after basal ganglion cerebral infarction. This association can be used in walking and balance assessment for stroke rehabilitation. Correcting forefoot pressure or the front and ant/post position can improve balance function.
RESUMO
BACKGROUND: Herpes simplex keratitis (HSK) is the most common but serious infectious keratitis with high recurrence. It is predominantly caused by herpes simplex virus type 1 (HSV-1). The spread mechanism of HSV-1 in HSK is not entirely clear. Multiple publications indicate that exosomes participate in the intercellular communication process during viral infections. However, there is rare evidence that HSV-1 spreads in HSK by exosomal pathway. This study aims to investigate the relationship between the spread of HSV-1 and tear exosomes in recurrent HSK. METHODS: Tear fluids collected from total 59 participants were included in this study. Tear exosomes were isolated by ultracentrifugation, then identified by silver staining and western blot. The size was determined by dynamic light scattering (DLS). The viral biomarkers were identified by western blot. The cellular uptake of exosomes was studied using labelled exosomes. RESULTS: Tear exosomes were indeed enriched in tear fluids. Collected exosomes own normal diameters consistent with related reports. The exosomal biomarkers existed in tear exosomes. Labelled exosomes were successfully taken up by human corneal epithelial cells (HCEC) in large numbers in a short time. After cellular uptake, HSK biomarkers were detectable by western blot in infected cells. CONCLUSIONS: Tear exosomes should be the latent sites of HSV-1 in recurrent HSK and might be involved in the spread of HSV-1. Besides, this study verifies HSV-1 genes can be indeed transferred between cells by exosomal pathway, providing new inspiration for the clinical intervention and treatment as well as the drug discovery of recurrent HSK.
RESUMO
A20, also called TNFAIP3, is a crucial regulator of inflammation in various diseases but has not evidenced its function in the cornea. We aimed to evaluate the existence and the functions of A20 in human corneal epithelial (HCE-T) cells. After being treated with lipopolysaccharide (LPS) in different concentrations or at separate times, cells were collected to analyze A20 expressions. We then constructed the A20 knockdown system by siRNA and the A20 overexpressing system by lentivirus transduction. Systems were further exposed to medium with or without LPS for indicated times. Next, we evaluated the production of inflammatory cytokines (IL-6 and IL-8) by qRT-PCR and ELISA. Also, the translocation of P65 and the phosphorylation of P65, P38 and JNK were observed in two systems. In addition, we used the nuclear factor kappa-B (NF-κB) antagonist TPCA-1 for the pretreatment in cells and then detected the A20 expressions. We found a low basal expression of A20 in HCE-T cells, and the expressions could be dose-dependently induced by LPS, peaking at 4 h in protein level after stimulation. Both the A20 knockdown and A20 overexpressing systems were confirmed to be effective. After the LPS treatment, productions of IL-6 and IL-8 were enhanced in the A20 knockdown system and reduced in the A20 overexpressing system. A20 reduced the translocation of P65 into the nucleus and the phosphorylation of P65, P38 and JNK. Furthermore, TPCA-1 pretreatment reduced the expression of A20 in cells. We concluded that A20 is a potent regulator for corneal epithelium's reaction to inflammation, and it thus is expected to be a potential therapy target for ocular surface diseases.
Assuntos
Interleucina-6 , Lipopolissacarídeos , Humanos , Células Epiteliais/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismoRESUMO
Background and purpose: Extracranial artery stenosis (ECAS) is associated with the presence of individual markers of cerebral small vessel disease (CSVD). Here, we investigated the relationship between severe extracranial artery stenosis or occlusion and CSVD in patients with large artery atherosclerotic (LAA) cerebral infarction. Methods: A total of 128 patients with LAA cerebral infarction who met our specific inclusion criteria were selected, including 92 males and 36 females. These patients were divided into three groups based on whether they had severe symptomatic extracranial arterial stenosis or occlusion, severe asymptomatic extracranial artery stenosis or occlusion, or severe extracranial artery stenosis or occlusion (both symptomatic and asymptomatic). Intra-group comparisons were then performed to examine whether there were any differences in the total CSVD scores and Fazekas scores. Results: Patients with severe extracranial arterial stenosis or occlusion and those with severe asymptomatic extracranial arterial stenosis or occlusion had a significantly higher total CSVD score (P < 0.05), but there were no significant differences between the groups in terms of Fazekas scores. Furthermore, there were no significant difference in the total CSVD scores and Fazekas scores when compared between patients with or without severe symptomatic extracranial arterial stenosis or occlusion. Conclusion: Severe stenosis or occlusion of the contralateral extracranial artery may increase the incidence of CSVD in patients with LAA cerebral infarction. Active and effective clinical intervention following comprehensive evaluation should be undertaken for unilateral cerebral infarction patients with severe stenosis or occlusion of the contralateral extracranial arterial.
RESUMO
Objective: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on the gait and postural control ability of patients with executive dysfunction (ED) after stroke. Methods: A total of 18 patients with ED after stroke were randomly assigned into two groups, including an experimental group and a sham group. Patients in both groups received routine rehabilitation therapy, and patients in the experimental group underwent rTMS on the left dorsolateral prefrontal cortex (DLPFC) for 2 weeks (5 HZ, 80%MT, 1200 pulses). In the sham group, patients experienced sham stimulation treatment, in which the coil was placed vertically with the head. Before and after treatment, patients in both groups were subjected to Montreal cognitive assessment (MoCA) scoring, Fugl−Meyer assessment of lower extremity (L-FMA), Stroop color-word test (SCWT), gait analysis, foot plantar pressure test, 10-m walking test (10MWT), Berg balance scale (BBS), and timed up and go test (TUGT). In the SCWT, it was attempted to record the time of each card (SCWT-T), the correct number (SCWT-C), Stroop interference effect-time (SIE-T), and SIE correct count (SIE-C). The TUGT was categorized into four stages: getting up (GT), walking straight (WT), turning around (TT), and sitting down (ST), in which the total time of TUGT was calculated. Results: After two weeks of treatment, the evaluation indexes were improved in the two groups, some of which were statistically significant. In the experimental group, SCWT-T, SIE-T, SIE-C, GT, WT, TT, ST, and TUGT were significantly improved after treatment (p < 0.05). SCWT-C, L-FMA score, 10MWT, GT, WT, stride length, step width, foot plantar pressure, pressure center curve, and activities of daily living were not statistically different from those before treatment (p > 0.05). After treatment, SCWT-T, SIE-C, SIE-T, BBS score, TT, and ST in the experimental group were significantly shorter than those before treatment, with statistical differences (p < 0.05). Compared with the sham group, SCWT-C, L-FMA score, 10MWT, GT, WT, TUGT, stride length, step width, foot plantar pressure, pressure center curve, and motor skills were not significantly improved (p > 0.05). Conclusion: It was revealed that post-stroke rTMS treatment of patients with ED could improve executive function, improve postural control function, and reduce the risk of falling. In addition, rTMS of DLPFC could be a therapeutic target for improving postural control ability and reducing the risk of falling.
RESUMO
Fibroblast growth factor 1 (FGF1) is an autocrine growth factor released from adipose tissue during over-nutrition or fasting to feeding transition. While local actions underlie the majority of FGF1's anti-diabetic functions, the molecular mechanisms downstream of adipose FGF receptor signaling are unclear. We investigated the effects of FGF1 on glucose uptake and its underlying mechanism in murine 3T3-L1 adipocytes and in ex vivo adipose explants from mice. FGF1 increased glucose uptake in 3T3-L1 adipocytes and epididymal WAT (eWAT) and inguinal WAT (iWAT). Conversely, glucose uptake was reduced in eWAT and iWAT of FGF1 knockout mice. We show that FGF1 acutely increased adipocyte glucose uptake via activation of the insulin-sensitive glucose transporter GLUT4, involving dynamic crosstalk between the MEK1/2 and Akt signaling proteins. Prolonged exposure to FGF1 stimulated adipocyte glucose uptake by MEK1/2-dependent transcription of the basal glucose transporter GLUT1. We have thus identified an alternative pathway to stimulate glucose uptake in adipocytes, independent from insulin, which could open new avenues for treating patients with type 2 diabetes.
Assuntos
Adipócitos , Fator 1 de Crescimento de Fibroblastos , Glucose , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismoRESUMO
Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.
Assuntos
Dermatite Atópica , PPAR gama , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Camundongos , Obesidade/metabolismo , PPAR gama/agonistas , PPAR gama/metabolismo , Medicina de Precisão , Análise de Sequência de RNA , Células Th2/metabolismoRESUMO
Intraocular lens (IOL) is the indispensable implant for cataract surgery. However, posterior capsular opacification (PCO) happens in high incidence after IOL implantation. PCO is caused by adhesion, proliferation, and trans-differentiation of the residual human lens epithelial cells (HLECs). Despite the great achievements in surface coating and antiproliferative drug loading on the intraocular lens (IOL) for effective PCO prevention, the complex fabrication process and potential toxicity of the drugs still limit their clinical applications and commercial mass production. In this investigation, a convenient and efficient photodynamic therapy (PDT) coating fabricated by facile yet economical and practical dopamine self-polymerization was applied to IOL surface modification for PCO prevention. The optical properties of IOL, such as light transmittance, imaging quality and refractive index, remain unchanged after modification. Using an in vitro cell assay, the parameters of PDT were optimized. The PDT coating shows excellent biocompatibility in darkness and eliminates LECs significantly under irradiation. The research on the cell elimination mechanism showed that reactive oxygen species (ROS) mainly induced cell apoptosis. In vivo experiments demonstrated that the implantation of modified IOLs can prevent PCO effectively. As a result, this work provides a safe, simple and effective PDT coating for the IOL surface to reduce the incidence of PCO.
Assuntos
Opacificação da Cápsula , Lentes Intraoculares , Fotoquimioterapia , Opacificação da Cápsula/prevenção & controle , Humanos , Indóis , PolímerosRESUMO
Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention. Herein, a new anti-adhesive IOL material was designed and successfully synthesized by radical copolymerization of ethylene glycol phenyl ether methacrylate (EGPEMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA). The physicochemical properties of P(EGPEMA-co-EA) copolymer materials, including chemical structure, mechanical, thermal, surface, and optical properties, were analyzed by using 1H NMR spectroscopy, FT-IR spectroscopy, tensile test, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), water contact angle measurement, and UV-vis spectroscopy. The elongation at break and the modulus of elasticity of the copolymer were tunable through the change of the composition of monomers. Compared to other components, the tensile results showed that P(EGPEMA-co-EA) materials (70% EGPEMA in mass ratio, F7) are suitable for the preparation of foldable intraocular lens with lower elastic modulus and higher elongation at break. TGA and DSC showed that the material has high thermal stability, and the glass transition temperature of F7 material is 16.1 °C. The water contact angle measurement results showed that the introduction of EA improved the hydrophilicity of the material. The percentage of transmittance of all copolymers at 400-800 nm is above 85%. Then, the biocompatibility of the materials was evaluated by in vitro assay and subcutaneous implantation. Both in vitro results and subcutaneous implantation experiments showed that the designed IOL materials exhibited a good anti-adhesion effect and no cytotoxicity. Finally, phacoemulsification and IOL intraocular implantation were performed, and the in vivo results confirmed the good PCO prevention ability as well as the biocompatibility of the new IOL materials.
Assuntos
Opacificação da Cápsula , Lentes Intraoculares , Adesivos , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/prevenção & controle , Humanos , Lentes Intraoculares/efeitos adversos , Polímeros/química , Complicações Pós-Operatórias/prevenção & controle , Desenho de Prótese , Espectroscopia de Infravermelho com Transformada de Fourier , Aderências Teciduais/complicações , ÁguaRESUMO
Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fator 1 de Crescimento de Fibroblastos/metabolismo , Humanos , Insulina/metabolismo , Lipólise/fisiologiaRESUMO
The fogging of the optical lenses seriously affects the life quality and safety, which is due to the gathering of the humid air into liquid droplets on the solid surface because of the temperature change. Superhydrophobic coating modification is an effective way to repel the water from surface. However, due to the specific application requirements, the transparency of optical lenses after coating modification is still the challenge for the application of such superhydrophobic coatings. In this work, a superhydrophobic and transparent surface coating was fabricated by the layer-by-layer self-assembly followed with fluorination. After poly(sodium 4-styrenesulfonate) and poly(allylamine hydrochloride) (PAH) multilayer precoating was generated on the surface, the different bilayers of SiO2 nanoparticles in different particle sizes and PAH multilayers were fabricated. The obtained polyelectrolytes-nanoparticle multilayers were fluorinated by a fluorinating agent. Such polyelectrolytes-nanoparticle multilayered coating renders obvious micro-nano composite structure, showing excellent superhydrophilicity, whereas such coating modified eyeglasses keeps excellent light transparency. The results of antifogging and defogging test also proved that the eyeglass modified with this coating had good antifogging and defogging performance. Therefore, such polyelectrolytes-nanoparticle multilayered coating with excellent superhydrophobic and transparent properties might provide a feasible approach for the practical antifogging application of optical lenses.
Assuntos
Nanopartículas , Dióxido de Silício , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tamanho da Partícula , Polieletrólitos , Dióxido de Silício/químicaRESUMO
Prostate cancer (PCa) seriously jeopardizes men's health worldwide. Dihydroartemisinin, which is an effective antimalarial agent, has shown potential anticancer effects in various human cancer cell lines, including PCa cells. However, the mechanisms underlying the anticancer activity of dihydroartemisinin are not fully understood. Ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1) is highly expressed in a variety of tumors and is negatively correlated with the prognosis of various tumors. We reported previously that UHRF1 is downregulated during apoptosis induced by dihydroartemisinin in PC-3 PCa cells. In this study, we transfected PC-3 cells with lentiviruses containing UHRF1 or shRNA-UHRF1. Then, the cells were treated with dihydroartemisinin at different concentrations. Our data showed that overexpression of UHRF1 promoted cell proliferation and migration in PC-3 cells, inhibited cell apoptosis, increased cell proportion in G2 phase, increased DNA methyltransferase 1 and decreased p16INK4A expression at mRNA and protein levels. Downregulation of UHRF1 produces the opposite results. Moreover, the phenomena caused by overexpression of UHRF1 were inhibited after dihydroartemisinin treatment. Compared with control cells, cells overexpressing UHRF1 can resist the proapoptotic and antiproliferative effects of dihydroartemisinin to a certain extent. The effects of UHRF1 knockdown were further aggravated by dihydroartemisinin treatment, but no statistically significant effect was observed with increasing drug concentration. Our results suggested that dihydroartemisinin decreases proliferation and migration but enhances apoptosis of PCa cells, likely by downregulating UHRF1 and upregulating p16INK4A.
Assuntos
Artemisininas/farmacologia , Proteínas Estimuladoras de Ligação a CCAAT/efeitos dos fármacos , Neoplasias da Próstata/patologia , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas de Silenciamento de Genes , Humanos , MasculinoRESUMO
Objectives: To observe the efficacy of botulinum toxin type A (BoNT-A) for the spasticity of the lower-limb post-stroke on gait and posture control. Methods: A total of 46 patients with hemiplegia gait were randomly divided into the experimental group (23 patients) and the control group (23 patients). In patients in the experimental group received injections of BoNT-A by electrical stimulation-guided. At the same time, patients of the two groups received routine physical therapy. Gait analysis, plantar pressure analysis, lower-limb Fugl-Meyer assessment (L-FMA), 10 meter walking test (10MWT), timed "Up and Go" test (TUGT), and modified Ashworth Scale assess (MAS) of the lower limbs were performed at 0, 1, 4, and 12 weeks after treatment. Results: At 1, 4, and 12 weeks after treatment, the L-FMA, stride length, speed, and TUGT significantly improved than 0 week in both groups. The L-FMA and peak of forefoot pressure, and MAS results in the experimental group were better than those in the control group at 4 and 12 weeks. The TUGT, speed, and stride length in experimental group was significantly shortened than that in control group at 1, 4, and 12 weeks. Conclusion: Botulinum toxin type A injection can improve motor functions of the lower limb, gait, spasticity, forefoot pressure, and posture control of patients after stroke.
RESUMO
OBJECTIVE: The purpose of the study was to observe the effects of executive dysfunction (ED) on gait and postural control during walking after stroke. METHODS: In this study, 34 subjects with stroke and ED (8 women and 26 men; age, 55.41 ± 7.89 years; time since stroke onset, 1.3 ± 0.12 months) were recruited. Stroop color-word test (SCWT), 10-meter walk test (10MWT), timed-up-and-go test (TUGT), and gait analysis were evaluated. The correlation among the correct number of Stroop tasks (SCWT-C), the number of time-consuming tasks (SCWT-T), the amount of interference (SIE-M and SIE-T) and posture control, and gait-related parameters was analyzed. RESULTS: The results indicated that SCWT-C was negatively correlated with 10MWT, TUGT, and bilateral symmetry (P < 0.05). However, there was no significant correlation between SCWT-C and stride (P > 0.05). A significant negative correlation was seen between SCWT-C and bilateral symmetry (P < 0.05). There was no significant correlation between SCWT-T and stride (P > 0.05). SCWT-T was positively correlated with TUGT, 10MWT, and bilateral symmetry (P < 0.05). SIE-T was positively correlated with TUGT and bilateral symmetry (P < 0.05). There was no significant correlation between SIE-T and 10MWT or stride (P > 0.05). SIE-M was positively correlated with TUGT and bilateral symmetry (P < 0.05). There was no significant correlation between SIE-T and 10MWT or stride (P > 0.05). CONCLUSIONS: ED is closely related to the decline in postural control and the occurrence of falls. In the early phases of stroke rehabilitation, physiotherapists should focus on the patients' executive function to accelerate the recovery of postural control.
RESUMO
The main reason for the failure of glaucoma drainage devices is the chronic inflammatory reaction caused by the poor biocompatibility of biomaterials, which leads to the migration and proliferation of scleral fibroblasts surrounding the devices thus forming the encapsulation that will block the aqueous humor drainage channel. In order to inhibit the reaction of scleral fibroblasts after glaucoma drainage device implantation, this study designed and fabricated a 5-fluorouracil (5-FU) loaded chitosan microtube (CMT) for glaucoma aqueous humor drainage. The CMTs were made by template based adsorption-precipitation method using chitosan with excellent biocompatibility as raw material due to its characteristic of pH dependent solubility. The physical properties of CMTs were investigated. The in vitro and in vivo biocompatibilities were studied as well. The developed drainage device is expected to possess the dual function of reducing intraocular pressure and inhibiting excessive fibrosis after glaucoma drainage device implantation, thereby providing a novel way for the research of glaucoma drainage devices.
Assuntos
Quitosana , Implantes para Drenagem de Glaucoma , Glaucoma , Fluoruracila , Glaucoma/tratamento farmacológico , Humanos , Pressão IntraocularRESUMO
Posterior capsular opacification (PCO) is an emerging complication in cataract phacoemulsification and intraocular lens (IOL) implantation surgery, mainly stemming from the adhesion, proliferation, and trans-differentiation of the post-surgery residual lens epithelial cells (LECs). Previous investigations have shown that an anti-proliferative drug eluting coating on the IOL surface provides an effective way to inhibit PCO. However, due to the undesirable elution of the anti-proliferative drug, the safety of such modification is one of the important issues to be solved. In this investigation, photodynamic coating was introduced into IOL surface modification. The photosensitizer chlorin e6 grafted α-cyclodextrin (α-CD-Ce6) was synthesized and self-assembled onto the poly(poly(ethylene glycol) methacrylate) (PPEGMA) brush established IOL surface via the supramolecular interaction between α-CD and poly(ethylene glycol) chains. The results of investigation into its optical properties, including transmittance, refractive index, and surface morphology, showed no obvious alterations after photodynamic coating modification on the IOL surface. The in vitro LEC behaviour investigation optimized the photodynamic therapy parameters when light illumination was used for the cell elimination on the photodynamic coating modified IOL. The results have also shown that this functional coating modification effectively eliminates the cells on the surface of the IOL material when treated with light illumination, whereas it keeps excellent cytocompatibility in the absence of light illumination. The investigation of the cell elimination mechanism shows that this kind of functional coating eliminates the adherent cells by ROS induced apoptosis. The in vivo implantation result confirms the excellent PCO inhibition effect, as well as their safety and biocompatibility to the surrounding tissues. As a result, the proposed photodynamic coating provides a safer and effective alternative of IOL modification for preventing PCO.