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1.
Plant Cell ; 36(9): 3751-3769, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38943676

RESUMO

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.


Assuntos
Parede Celular , Etilenos , Regulação da Expressão Gênica de Plantas , Glucosiltransferases , Oryza , Proteínas de Plantas , Raízes de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Parede Celular/metabolismo , Etilenos/metabolismo , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Glucanos/metabolismo , Xilanos/metabolismo , Celulose/metabolismo
2.
Nanotechnology ; 35(41)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39008958

RESUMO

The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 hin vivoeven at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.


Assuntos
Vetores Genéticos , Glutationa , Polietilenoimina , Transfecção , Polietilenoimina/química , Transfecção/métodos , Glutationa/metabolismo , Glutationa/química , Animais , Humanos , Vetores Genéticos/química , Vetores Genéticos/genética , Manitol/química , Camundongos , Caveolina 1/metabolismo , Caveolina 1/genética , Terapia Genética/métodos , Técnicas de Transferência de Genes , Dissulfetos/química
3.
Facial Plast Surg ; 39(3): 300-306, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36191597

RESUMO

Nasolabial folds (NLFs) are the most pronounced sign of facial aging. This study explored the efficacy and safety of polycaprolactone gel in treating Chinese patients with moderate-to-severe NLFs. Patients with moderate-to-severe NLF who wished to be treated by dermal fillers were recruited from three centers between July 2017 and September 2019. The randomizing ratio was 1:1 in the polycaprolactone group (polycaprolactone injection) or control group (sodium hyaluronate gel injection). The primary endpoint was the effectiveness rate of Wrinkle Severity Rating Score (WSRS) scores at 12 months after injection. The full-analysis set (FAS) and safety sets had 80 patients in the polycaprolactone group and control group, respectively. In the FAS, the effectiveness rate at 12 months in the polycaprolactone group was 88.8% compared with 23.8% in controls (P < 0.001). The improvement in WSRS sustained during 12 months in the polycaprolactone group, while gradually vanished in the control group since 3 months after surgery. The global aesthetic improvement scale (GAIS) by investigator assessments was improved, much improved, or very much improved in all patients during follow-up, while the proportion of patients with a "no change" assessment gradually increased during follow-up after 6 months in the control group. The rates of injection-related adverse event (AE) and serve injection-related AE were 8.8 versus 11.3% and 0 versus 1.3% in the polycaprolactone group and control groups, respectively. Polycaprolactone gel injection is effective and safe to treat moderate-to-severe NLFs in Chinese patients.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Envelhecimento da Pele , Humanos , Sulco Nasogeniano , Estudos Prospectivos , Estética Dentária , Poliésteres/efeitos adversos , Ácido Hialurônico/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Resultado do Tratamento , Preenchedores Dérmicos/efeitos adversos
4.
Photodermatol Photoimmunol Photomed ; 38(1): 53-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34273202

RESUMO

OBJECTIVE: To study the clinical efficacy, recurrence rate and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with microneedle or CO2 lattice laser (CO2FL), in comparison with intrascar betamethasone injection in the treatment of hypertrophic acne scar. METHODS: Fifty-two patients with hypertrophic acne scars at the mandibular angle were enrolled and assigned to different therapy groups. Sixteen patients were treated with microneedle-assisted incorporation of ALA. Twenty-eight patients underwent CO2FL-assisted incorporation of ALA. Eight patients received standard therapy with intrascar injection of glucocorticoid. Two dermatologists, blinded to the therapy groups, independently evaluated the scars in all patients using the average value of the Vancouver Scar Scale score, which was treated as an integer variable. RESULTS: After three rounds of treatment, there was no significant difference in therapeutic effective rate among the microneedle, laser and topical glucocorticoid groups (93.75% vs 100% vs 100%, P = .855). One out of 16 patients (6.25%) in the microneedle group, no patient (0%) in the laser group and two out of eight patients (25%) in the topical glucocorticoid group had recurrence. The laser group showed a higher rate of adverse effects, which were usually mild and reversible, except for pigmentation. Adverse reactions could be completely subsided within 3 weeks. CONCLUSIONS: Either CO2FL or microneedle combined ALA-PDT for hypertrophic scar, as to topical glucocorticoid therapy, showed equivalent clinical effects but lower recurrence rate within 6 months of follow-up period.


Assuntos
Acne Vulgar , Cicatriz Hipertrófica , Lasers de Gás , Fotoquimioterapia , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Ácido Aminolevulínico , Dióxido de Carbono , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Humanos , Resultado do Tratamento
5.
Liver Int ; 41(9): 2032-2045, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33896094

RESUMO

BACKGROUND & AIMS: The effectiveness and safety of peginterferon alpha (peg-IFN-α) monotherapy in inactive hepatitis B virus (HBV) carriers (IHCs) have not been fully evaluated. METHODS: This observational study prospectively enrolled 298 IHCs in China from 2015 to 2019. Participants were given the right to choose to either receive peg-IFN-α monotherapy (treatment group, n = 142) or be monitored without treatment (control group, n = 156) according to their wishes. The scheduled treatment duration was 48 weeks. All participants were followed up to 72 weeks. The main efficacy endpoint was hepatitis B surface antigen (HBsAg) clearance at 72 weeks. RESULTS: Baseline characteristics were similar between both groups. At 72 weeks, intention-to-treat analysis showed that the rates of HBsAg clearance and seroconversion of the treatment group were 47.9% (68/142) and 36.6% (52/142), respectively, which were significantly higher than the HBsAg clearance rate of 1.9% (3/156) and the seroconversion rate of 0.6% (1/156) in the control group (both P < .001). Baseline HBV DNA < 20 IU/mL, lower HBsAg levels at baseline, 12 and 24 weeks, alanine aminotransferase elevation at 12 weeks, and greater HBsAg reduction from baseline to 12 and 24 weeks were independent predictors of HBsAg clearance. Generally, the therapy was well tolerated. Only five participants discontinued therapy as a result of peg-IFNα-related adverse events. CONCLUSIONS: Peg-IFN-α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.


Assuntos
Hepatite B Crônica , Antivirais/efeitos adversos , China , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
6.
Macromol Rapid Commun ; 41(19): e2000292, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32833274

RESUMO

Flexible electronics require its substrate to have adequate thermal stability, but current thermally stable polymer substrates are difficult to be disintegrated and recycled; hence, generate enormous electronic solid waste. Here, a thermally stable and green solvent-disintegrable polymer substrate is developed for flexible electronics to promote their recyclability and reduce solid waste generation. Thanks to the proper design of rigid backbones and rational adjustments of polar and bulky side groups, the polymer substrate exhibits excellent thermal and mechanical properties with thermal decomposition temperature (Td,5% ) of 430 °C, upper operating temperature of over 300 °C, coefficient of thermal expansion of 48 ppm K-1 , tensile strength of 103 MPa, and elastic modulus of 2.49 GPa. Furthermore, the substrate illustrates outstanding optical and dielectric properties with high transmittance of 91% and a low dielectric constant of 2.30. Additionally, it demonstrates remarkable chemical and flame resistance. A proof-of-concept flexible printed circuit device is fabricated with this substrate, which demonstrates outstanding mechanical-electrical stability. Most importantly, the substrate can be quickly disintegrated and recycled with alcohol. With outstanding thermally stable properties, accompanied by excellent recyclability, the substrate is particularly attractive for a wide range of electronics to reduce solid waste generation, and head toward flexible and "green" electronics.


Assuntos
Eletrônica , Polímeros , Eletricidade , Solventes , Temperatura
7.
J Gastroenterol Hepatol ; 35(9): 1488-1494, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32128877

RESUMO

BACKGROUND AND AIM: Additional simethicone (SIM) can improve adequate bowel preparation and adenoma detection rate (ADR). However, there is no consensus on the optimal dose of SIM. In this study, we compared the adequate bowel preparation rate with supplementation of split-dose 2 L polyethylene glycol (PEG) with low-dose SIM (200 mg) versus high-dose SIM (1200 mg). METHODS: This was a prospective, randomized, observer-blinded trial involving consecutive subjects undergoing colonoscopy. The primary outcome was adequate bowel preparation as assessed by Boston Bowel Preparation Scale (BBPS) score. RESULTS: Four hundred subjects were randomly allocated to low-dose SIM or high-dose SIM group. Baseline characteristics were comparable in the two groups (P > 0.05). No significant between-group differences were observed with respect to total bubble scale (BS) (8.49 ± 1.00 vs 8.39 ± 1.10, P = 0.07), total BBPS score (8.70 ± 0.81 vs 8.29 ± 1.18, P = 0.98), ADR (33.68% vs 31.79%, P = 0.69) or withdrawal time (13 [range, 10-16] min vs 13 [10-15] min, P = 0.96). The intubation time in low-dose SIM group was significantly shorter than that in high-dose SIM group (8 (4-16) min vs 10 [6-17] min, P = 0.04). In addition, BS scores as well as diminutive ADR in right colon were superior in the low-dose SIM group (2.68 ± 0.59 vs 2.52 ± 0.73, P = 0.03 and 54.29% vs 30.30%, P = 0.046, respectively). CONCLUSION: Addition of low-dose SIM to split-dose 2 L PEG was as effective as addition of high-dose SIM with respect to adequate bowel preparation, ADR and patient tolerance. However, low-dose SIM was superior with respect to intubation time, right colon BS scores, right colon diminutive ADR and cost savings.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Polietilenoglicóis/administração & dosagem , Simeticone/administração & dosagem , Adenoma/diagnóstico , Adulto , Catárticos/química , Colonoscopia/economia , Neoplasias Colorretais/diagnóstico , Redução de Custos , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
8.
J Environ Sci (China) ; 77: 97-103, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30573110

RESUMO

A plant bio-electrochemical system (PBES) was constructed for organic pollutant removal and power generation. The bio-cathode, composed of granular activated carbon (GAC), stainless wire mesh and a plant species (Triticum aestivum L.), was able to catalyze cathodic reactions without any requirement for aeration or power input. During the 60-day-long operation, an average voltage of 516 mV (1000 Ω) and maximum power density (Pmax) of 0.83 W/m3 were obtained in the PBES. The total nitrogen removal and total organic carbon removal in the PBES were 85% and 97%, respectively. Microbial community analyses indicated that bacteria associated with power generation and organic removal were the predominant species in the bio-cathode, and plant-growth-promoting rhizobacteria were also found in the PBES. The results suggested that the coupling of plants with the GAC cathode may enhance the organic-matter degradation and energy generation from wastewater and therefore provide a new method for bio-cathode design and promote energy efficiency.


Assuntos
Eletroquímica/instrumentação , Microbiota , Nitrogênio/isolamento & purificação , Nitrogênio/metabolismo , Raízes de Plantas/química , Triticum/química , Carvão Vegetal/química , Eletrodos , Nitrogênio/química , Aço Inoxidável/química
9.
Pharm Res ; 33(1): 217-36, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26334502

RESUMO

PURPOSE: Emodin (EMO) has multi-targets and multi-way antitumor effect, which was limited by the instability and poor solubility of EMO. The aim of this study was to formulate EMO-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (EPTN) to increase the liver targeting of EMO for cancer therapy. METHODS: EMO/coumarin-6-loaded PLGA-TPGS nanoparticles (ECPTN) and EMO-loaded PLGA nanoparticles (EPN) were also prepared as comparison. The cellular uptake of ECPTN by HepG2 and HCa-F cells was investigated using Confocal laser scanning microscopy. The apoptosis of HepG2 cells handled with EPTN was assayed by flow cytometry. The liver targeting property of ECPTN in mice was evaluated using the drug concentration determined by RP-HPLC and the freezing slices were investigated via fluorescence inversion microscopy. The blood samples were obtained from vein intubation to illustrate the pharmacokinetics process of EPTN. The tumor-bearing mice model was established to elucidate the in vivo therapeutic effect of EPTN. RESULTS: The results demonstrated that ECPTN could be internalized by HepG2 and HCa-F cells respectively. The ratio of apoptosis cells was increased after dealing with EPTN. The detection indexes of drug concentration and fluorescence inversion microscopy images indicated ECPTN had an excellent effect on liver targeting property than EMO solutions (EMS). The pharmacokinetics process of EPTN showed obvious sustained-release effect than EMS. Compared with EPN, the in vivo antitumor activity of EPTN against tumor cells were better. CONCLUSIONS: In conclusion, EPTN could be used in the treatment of liver cancer acted as a kind of promising intravenous dosage forms.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Emodina/administração & dosagem , Emodina/uso terapêutico , Ácido Láctico/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Polietilenoglicóis/química , Ácido Poliglicólico/química , alfa-Tocoferol/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Emodina/farmacocinética , Humanos , Camundongos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Sprague-Dawley
10.
Drug Dev Ind Pharm ; 41(7): 1193-203, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25026246

RESUMO

OBJECTIVES: Hepatocellular carcinoma is the third most common cause of cancer death. Oleanolic acid (OA) is a natural triterpenoid, has many important biological actions, including antitumor effect, but its poor solubility often leads to poor pharmacodynamics. The aim of our work is to make OA-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (OPTN) to improve its efficacy to liver cancer and characterize it. METHODS: OPTN were prepared by ultrasonic emulsification-solvent evaporation technique using PLGA with or without the addition of TPGS (OPN). The coumarin-6-loaded nanoparticles were used as a fluorescence marker. The nanoparticles were characterized for surface morphology, surface charge, particle size, drug loading, encapsulation efficiency, in vitro drug-release, cellular uptake, cytotoxicity by human liver cancer cell line HepG2 cells, and therapeutic effect in vivo. KEY FINDINGS: The prepared nanoparticles were found to be spherical in shape. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake and cytotoxicity of OPTN in the HepG2 cells compared with that of OPN. The treatment of OPTN group was better than OPN and FS groups in vivo. CONCLUSION: The results showed advantages of OPTN in terms of sustainable release and efficacy in liver cancer chemotherapy compared with OPN. OPTN could be acted as a novel and new dosage form to be used in cancer treatment study.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas , Ácido Oleanólico/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Cumarínicos/administração & dosagem , Cumarínicos/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Células Hep G2 , Humanos , Ácido Láctico/química , Neoplasias Hepáticas/patologia , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Tiazóis/administração & dosagem , Tiazóis/química , Vitamina E/análogos & derivados , Vitamina E/química
11.
Drug Dev Ind Pharm ; 40(11): 1557-64, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24059282

RESUMO

OBJECTIVES: This paper describes the development and optimization of curcumin thermosensitive hydrogels (CTH), a kind of gel injection for intratumoral injection treatment. METHODS: Aimed at increasing the content and stability of effective components, an optimal formulation of CTH was chosen based on the results from orthogonal tests and the optimal pH was determined by stability test. To investigate the hydrogels drug release in vitro, residence time by RP-HPLC and therapeutic effects on ascitic hepatocarcinoma cell strain with high metastasis potential in lymphatic system (HCA-F) solid tumors in mice. KEY FINDINGS: The selected optimal formulation of CTH was: 0.2% curcumin, 20% poloxamer 407, 4% poloxamer 188, 8% polyethylene glycol 400, 12% 1,2-propanediol and pH was 6.0. The drug release determined by RP-HPLC fit to the Higuchi model. The residence time of CTH was longer than the curcumin suspensions. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice. CONCLUSIONS: The CTH prepared in this test demonstrates proper gel temperature and viscosity. It improves the solubility of curcumin with a relatively long period of drug release in vitro and residence time. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacologia , Hidrogéis/química , Poloxâmero/química , Polietilenoglicóis/química , Animais , Química Farmacêutica , Cromatografia de Fase Reversa , Portadores de Fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Camundongos , Temperatura , Viscosidade
12.
Wei Sheng Wu Xue Bao ; 54(1): 53-61, 2014 Jan 04.
Artigo em Zh | MEDLINE | ID: mdl-24783854

RESUMO

OBJECTIVE: The gene diversity of the bacterial 48 family glycoside hydrolase (GH48) in rumen environment was studied and new gene resources for efficient cellulose degradation were provided. METHODS: A pair of gh48 degenerate primers was designed through sequences alignment of the gh48 gene sequences from ruminal Ruminococcus. The total DNA and RNA were extracted from two rumen samples and cDNA was synthetized through reverse transcription from total RNA. Four gh48 gene clone libraries were constructed and analyzed. RESULTS: In total 455 gh48 gene sequences were obtained from the 4clone libraries. Sequence similarity among the 455 gene sequences varies between 58.65% and 100%. They fell into 66 species with the sequence similarity > or = 89%, and divided into 5 different clusters. OTU65 in cluster C represents an abundant gh48 gene which in both DNA and cDNA clones libraries, accounting for 36.4% and 19.5% respectively. Our study reveals rich gene diversity of the 48 family glycoside hydrolase and provided new gene resources for cellulose degradation.


Assuntos
Bactérias/enzimologia , Bactérias/genética , Variação Genética , Glicosídeo Hidrolases/genética , Família Multigênica/genética , Rúmen/microbiologia , Animais , Bactérias/metabolismo , Bovinos , Celulose/metabolismo , Clonagem Molecular , Glicosídeo Hidrolases/metabolismo , Reação em Cadeia da Polimerase , Análise de Sequência
13.
PLoS One ; 19(2): e0296940, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306390

RESUMO

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).


Assuntos
Mesalamina , Espectrometria de Massas em Tandem , Humanos , Administração Oral , Área Sob a Curva , China , Cromatografia Líquida , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Mesalamina/efeitos adversos , Espectrometria de Massas em Tandem/métodos
14.
J Microencapsul ; 30(5): 432-40, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23517067

RESUMO

The aim of this study was to develop poly(D,L-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles formulations for improved oral delivery of exemestane. Exemestane-loaded PLGA nanoparticles and PLGA/MMT nanoparticles were prepared by a modified solvent extraction/evaporation technology with vitamin E succinated polyethylene glycol 1000 (TPGS) as emulsifier. The content of MMT was estimated by thermal gravimetric analysis. The drug encapsulation efficiency and in vitro drug release kinetics were measured by high-performance liquid chromatography. The size, size distribution, surface charge and morphology of the exemestane-loaded nanoparticles were characterized using a Zetasizer Nano ZS and field emission scanning electron microscopy. The physical status of exemestane in the nanoparticles was characterized by differential scanning calorimetry. In vitro cellular uptake of coumarin-6-loaded nanoparticles was investigated by confocal laser scanning microscope, demonstrating that the fluorescence nanoparticles were internalized by Caco-2 cells (as an in vitro gastrointestinal model). The results of in vitro cytotoxicity experiment on MCF-7 cells (as a model of breast cancer cells) showed the exemestane-loaded nanoparticles resulted in lower cell viability versus the pure exemestane solution. The cytotoxicity against MCF-7 cells for exemestane-loaded nanoparticles and pure exemestane solution was dependent on the drug concentration and incubation time. In conclusion, this study indicates the capability of PLGA nanoparticles and PLGA/MMT nanoparticles in enhancing the oral delivery of exemestane.


Assuntos
Androstadienos/administração & dosagem , Antineoplásicos/administração & dosagem , Bentonita/química , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Androstadienos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Células CACO-2 , Linhagem Celular Tumoral , Feminino , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
15.
IEEE J Biomed Health Inform ; 27(12): 5827-5836, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37751334

RESUMO

Research on orthodontic treatment monitoring from oralscan video is a new direction in dental digitalization. We designed an approach to reconstruct, segment, and estimate the pose of individual teeth to measure orthodontic treatment. To handle the semantic gap in heterogeneous data on the condition that they are combined linearly, we present a multimedia interaction network (MIN) to combine heterogeneous information in point cloud segmentation by extending the graph attention mechanism. Moreover, a structure-aware quadruple loss is designed to explore the relation between multiple and diverse unmatched points in point cloud registration. The performance of our approach is evaluated on multiple tooth registration datasets, and extensive experiments show that our approach improves the accuracy by a margin of 1.4% in the inlier ratio on the Aoralscan3 dataset when it is compared with prevailing approaches.


Assuntos
Ortodontia , Dente , Gravação em Vídeo , Humanos , Dente/diagnóstico por imagem
16.
J Hazard Mater ; 454: 131470, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37116333

RESUMO

Nanoplastics (NPs) are the novel hazardous materials and ubiquitous in environment with different sizes. Although recent studies showed testicular toxicity of PS-NPs, whether and how NPs affect male fertility and whether they have the size-dependent effect remain ambiguous in mammals. In this study, the male mice were orally exposed to 25-, 50-, and 100-nm polystyrene NPs (PS-NPs) for 56 days. All three sized PS-NPs reduced male fertility and even caused male infertility. They accumulated in the testes, induced oxidative stress, affected the expression of apoptosis- and inflammation-related genes, and compromised energy metabolism, resulting in damaged testicular microstructure and functions. PS-NPs caused more severe testicular toxicity in infertile mice than in fertile mice. In addition, PS-NPs inhibited sperm capacitation and capacitation-dependent processes in infertile mice but not in fertile mice. In infertile mice, PS-NPs reduced the sperm levels of two Rho GTPases (RAC1 and CDC42) via increasing their ubiquitination levels and diminished sperm filamentous actin polymerization, thus inhibiting sperm capacitation. However, these testicular and sperm toxicities showed no size-dependent effect among three sized PS-NPs. In conclusion, PS-NPs inhibit male fertility by their multifaceted toxicity on testes and sperm in mice, providing novel insights into reproductive risks of NPs to mammals.


Assuntos
Infertilidade Masculina , Nanopartículas , Humanos , Masculino , Animais , Camundongos , Testículo/metabolismo , Poliestirenos/metabolismo , Microplásticos/metabolismo , Sêmen , Espermatozoides , Infertilidade Masculina/induzido quimicamente , Fertilidade , Nanopartículas/toxicidade , Nanopartículas/metabolismo , Mamíferos/metabolismo
17.
Adv Healthc Mater ; 12(32): e2302094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37827986

RESUMO

Gene therapy based on miRNAs has broad application prospects in the treatment of tumors. However, due to degradation and ineffective release during intracellular transport, current gene delivery vectors used for miRNAs limited their actual transfection efficiency. This study develops a novel nonviral vector PEI-SPDP-Man (PSM) that can simultaneously target cellular uptake pathways and intracellular responsive release for miR-34a. PSM is synthesized by connected mannitol (Man) to branched polyethylenimine (PEI) using a disulfide bond. The prepared PSM/miR-34a gene delivery system can induce and enter to tumor cells through caveolae-mediated endocytosis to reduce the degradation of miR-34a in lysosomes. The disulfide bond is sensed at high concentration of glutathione (GSH) in the tumor cells and miR-34a is released, thereby reducing the expression of Bcl-2 and CD44 to suppress the proliferation and invasion of tumor cells. In vitro and in vivo experiments show that through the targeted cellular uptake and the efficient release of miR-34a, an effective antitumor and antimetastasis profiles for the treatment of orthotopic triple negative breast cancer (TNBC) are achieved. This strategy of controlling intracellular transport pathways by targeting cellular uptake pathways in the gene therapy is an approach that could be developed for highly effective cancer therapy.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Polímeros , Cavéolas/metabolismo , Cavéolas/patologia , MicroRNAs/metabolismo , Técnicas de Transferência de Genes , Endocitose , Dissulfetos , Proliferação de Células
18.
Water Res ; 218: 118429, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35483206

RESUMO

Electrode materials occupy most of the construction cost of the microbial electrochemical system (MES), and the low mechanical strength and poor electrochemical performance of the commonly used traditional carbon-based materials restrict the promotion and application of this technology. In this study, polymer-based three-dimensional (3D) honeycomb-structure (HS) materials with good mechanical properties were used as supporting materials. Graphene (GR), carbon nanotube (CNT), and polypyrrole (PPy) was separately chosen as a surface conductivity coating layer for preparing MES anodes. The introduction of GR, CNT, and PPy on HS increased surface roughness, hydrophilicity, O and N content, electrochemically active surface area, and decreased charge transfer internal resistance, which promoted the adhesion of microorganisms on their surface and enhanced the extracellular electron transfer process at the electrode/microbe interface. The CNT-HS anode system got the better maximal power density (1700.7 ± 149.0 mW/m2) of the three modified anode systems and 3.60 times that of MES using CC (471.8 ± 27.2 mW/m2) as the anode. The accelerated reactions of the redox species in the outer cell membrane, the promoted electron shuttle secretion, and the enhanced abundance of the tricarboxylic acid cycle-related functional genes in biofilm led to better performance of the CNT-HS anode system. The CNT-HS anode system also exhibited long-term operational stability (>6 months) and a good chemical oxygen demand degradation effect. Furthermore, CNT-HS material exhibited its cost advantage, and its projected cost is estimated to be about $1.8/m2, much lower than the currently used MES anodes ($8.2-548.2/m2). Considering the good mechanical properties, simple preparation process, low manufacturing cost, long-term stability, excellent bio-electrochemical performance, and good pollutant removal ability, HS-based anode has promising potential for high-performance MES in applications.


Assuntos
Fontes de Energia Bioelétrica , Poluentes Ambientais , Grafite , Nanotubos de Carbono , Eletrodos , Nanotubos de Carbono/química , Polímeros , Pirróis
19.
PLoS Negl Trop Dis ; 16(1): e0010090, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35041675

RESUMO

BACKGROUND: This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explored the influence of gene methylation and polymorphism on EV71-HFMD. METHODOLOGY/PRINCIPAL FINDINGS: 60 healthy controls and 120 EV71-HFMD patients, including 60 mild EV71-HFMD and 60 severe EV71-HFMD patients, were enrolled. First, MiSeq was performed to explore the methylation of CpG islands in the DDX58 and IFIH1 promoter regions. Then, DDX58 and IFIH1 expression were detected in PBMCs using RT-qPCR. Finally, imLDR was used to detect DDX58 and IFIH1 single-nucleotide polymorphism (SNP) genotypes. Severe EV71-HFMD patients exhibited higher DDX58 promoter methylation levels than healthy controls and mild EV71-HFMD patients. DDX58 promoter methylation was significantly associated with severe HFMD, sex, vomiting, high fever, neutrophil abundance, and lymphocyte abundance. DDX58 expression levels were significantly lower in mild patients than in healthy controls and lower in severe patients than in mild patients. Binary logistic regression analysis revealed statistically significant differences in the genotype frequencies of DDX58 rs3739674 between the mild and severe groups. GeneMANIA revealed that 19 proteins displayed correlations with DDX58, including DHX58, HERC5, MAVS, RAI14, WRNIP1 and ISG15, and 19 proteins displayed correlations with IFIH1, including TKFC, IDE, MAVS, DHX58, NLRC5, TSPAN6, USP3 and DDX58. CONCLUSIONS/SIGNIFICANCE: DDX58 expression and promoter methylation were associated with EV71 infection progression, especially in severe EV71-HFMD patients. The effect of DDX58 in EV71-HFMD is worth further attention.


Assuntos
Proteína DEAD-box 58/genética , Metilação de DNA/genética , Doença de Mão, Pé e Boca/patologia , Helicase IFIH1 Induzida por Interferon/genética , Receptores Imunológicos/genética , Criança , Pré-Escolar , Ilhas de CpG/genética , Proteína DEAD-box 58/metabolismo , Enterovirus Humano A , Feminino , Predisposição Genética para Doença/genética , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Helicase IFIH1 Induzida por Interferon/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Receptores Imunológicos/metabolismo , Índice de Gravidade de Doença
20.
Eur Radiol ; 20(11): 2732-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20700595

RESUMO

To evaluate whether Willis covered stent implantation yielded angiographic and clinical results were better than those with coil embolization. Eighty-nine patients with cranial internal carotid artery (CICA) aneurysms were treated nonrandomly with covered stents (n = 43, group A) or coil embolization (n = 46, group B). Data on the technical success, procedure time, initial and final angiographic results, and final clinical outcomes were collected and analyzed at >6 months post-procedure. Covered stent placement and coil embolization were successful in all patients, except for one patient in group A. The initial angiographic results showed complete occlusion in 34 group-A patients (80.9%; 95% CI: 69%, 93%) and 24 group-B patients (52.2%; 95% CI: 37%, 67%) (P = 0.004). The final angiographic results indicated complete occlusion in 39 group A patients (39/41, 95.1%; 95% CI: 88%, 102%) and 22 group B patients (48.9%; 95% CI: 34%, 64%) (P < 0.001). The average procedure time was shorter in group A than that in group B (P < 0.001). CICA aneurysm treatment with covered stents yielded better intermediate-term angiographic outcome than those with the recommended approach of coil embolization. (ClinicalTrials.gov number, NCT01029938).


Assuntos
Doenças das Artérias Carótidas/terapia , Artéria Carótida Interna , Embolização Terapêutica/efeitos adversos , Aneurisma Intracraniano/terapia , Stents , Adolescente , Adulto , Idoso , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Criança , Materiais Revestidos Biocompatíveis , Embolização Terapêutica/instrumentação , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
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