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1.
Open Life Sci ; 19(1): 20220867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756857

RESUMO

Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

2.
Molecules ; 29(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38611885

RESUMO

Mesoporous titanium nanoparticles (MTN) have always been a concern and are considered to have great potential for overcoming antibiotic-resistant bacteria. In our study, MTN modified with functionalized UV-responsive ethylene imine polymer (PEI) was synthesized. The characterization of all products was performed by different analyses, including SEM, TEM, FT-IR, TGA, XRD, XPS, and N2 adsorption-desorption isotherms. The typical antibacterial drug berberine hydrochloride (BH) was encapsulated in MTN-PEI. The process exhibited a high drug loading capacity (22.71 ± 1.12%) and encapsulation rate (46.56 ± 0.52%) due to its high specific surface area of 238.43 m2/g. Moreover, UV-controlled drug release was achieved by utilizing the photocatalytic performance of MTN. The antibacterial effect of BH@MTN-PEI was investigated, which showed that it could be controlled to release BH and achieve a corresponding antibacterial effect by UV illumination for different lengths of time, with bacterial lethality reaching 37.76% after only 8 min of irradiation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles have also been studied. The MIC of BH@MTN-PEI was confirmed as 1 mg/mL against Escherichia coli (E. coli), at which the growth of bacteria was completely inhibited during 24 h and the concentration of 5 mg/mL for BH@MTN-PEI was regarded as MBC against E. coli. Although this proof-of-concept study is far from a real-life application, it provides a possible route to the discovery and application of antimicrobial drugs.


Assuntos
Berberina , Nanopartículas , Berberina/farmacologia , Liberação Controlada de Fármacos , Escherichia coli , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/farmacologia , Antibacterianos/farmacologia
3.
Curr Drug Deliv ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38310438

RESUMO

BACKGROUND: Breviscapine (BVP) is one of the extracts of several flavonoids of Erigeron breviscapus, which has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease, and angina pectoris. But BVP has poor solubility. OBJECTIVE: The objective of the study is to develop mesoporous silica nanoparticles (MSNs) that can be loaded with a drug with poor water solubility. The MSNs, which were designed for oral administration, enhanced both the dissolution rate and drug loading capacity. METHODS: The use of MSNs as an oral drug delivery system was investigated by SEM, TEM, BETBJH, XRD, FT-IR, and HPLC. Additionally, we examined the oral bioavailability of BVP loaded onto MSNs and examined the cellular cytotoxicity of MSNs. RESULTS: The results indicate that the oral bioavailability of BVP after loading onto MSNs was greater than that of a marketed product. Furthermore, we studied the mechanism by which MSNs enhance the oral absorption of BVP. CONCLUSION: MSNs have the potential to enhance the oral bioavailability of poorly water-soluble drugs by accelerating the drug dissolution rate.

4.
Int J Biol Macromol ; 256(Pt 1): 128431, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029896

RESUMO

In this study, carboxymethyl chitosan (CMCS) with excellent biocompatibility was used as the "gatekeeper" to design and fabricate a pH-responsive drug delivery system (CMCS-DFNS) as paclitaxel carriers. Characterization results showed that CMCS-DFNS was successfully prepared and the nanocarriers displayed excellent drug loading efficiency of 19.8 %, and the results of the adsorption mechanism revealed that the adsorption of PTX was consistent with the Freundlich isotherm and pseudo-second-order kinetic model. Furthermore, the pH-responsive controlled release behavior at different pH (pH = 7.4, 6.5, and 5.0) was evaluated, and the results demonstrated that the cumulative release at pH 5.0 was 58.8 %, which was 2.7 times higher than that at pH 7.4, suggesting that the carrier exhibited a good pH sensitivity. The results of in vitro cellular experiments further indicated that CMCS-DFNS significantly improved the drug uptake efficiency in breast cancer MCF-7 cells. Importantly, the results of in vivo and cellular pharmacokinetic revealed that CMCS-DFNS can improve the circulation time and enhance the relative bioavailability of paclitaxel. Therefore, the fabricated pH-responsive drug delivery system has potential applications in the delivery of anti-tumor drugs, and provides a new delivery pathway for other compounds with low bioavailability.


Assuntos
Antineoplásicos , Quitosana , Humanos , Paclitaxel/farmacocinética , Preparações de Ação Retardada/farmacologia , Quitosana/química , Dióxido de Silício , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio
5.
Int J Endocrinol ; 2023: 9373043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077930

RESUMO

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient's bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians' understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.

6.
Clin Spine Surg ; 36(8): E362-E368, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37296489

RESUMO

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To explore the related factors of vertebral height loss (VHL) after pedicle screw fixation of thoracolumbar fracture and to determine the optimum prediction point. SUMMARY OF BACKGROUND DATA: With the widespread application of thoracolumbar fracture internal fixation, VHL after the operation is increasingly presented. However, there is no unified conclusion on the specific cause of VHL and how to predict it. METHODS: A total of 186 patients were selected and divided into the loss group (n = 72) and the not-loss group (n = 114) according to whether the fractured vertebral height was lost after the operation. The two groups were compared concerning sex, age, body mass index, osteoporosis self-assessment tool for Asians (OSTA), fracture types, number of fractured vertebrae, preoperative Cobb angle and compression degree, number of screws, and extent of vertebral restore. Univariate analysis and Multivariate logistic regression analysis were performed to identify the independent factors for the VHL with the receiver operating characteristic curve and the optimal prediction value was calculated according to area under the curve. RESULTS: Multivariate logistic regression analysis showed that OSTA ( P < 0.05) and preoperative vertebral compression ( P < 0.05) were significantly correlated with postoperative VHL, which were independent risk factors for postoperative VHL. The OSTA of 2.32 and the preoperative vertebral compression degree of 38.5% were the best prediction points for postoperative VHL based on the Youden Index analysis. CONCLUSIONS: The OSTA and preoperative vertebral compression were independent risk factors for VHL. The risk of postoperative VHL was significantly higher when the OSTA was ≤2.32 or the preoperative vertebral compression was ≥38.5%. LEVEL OF EVIDENCE: Level III.


Assuntos
Fraturas por Compressão , Parafusos Pediculares , Fraturas da Coluna Vertebral , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fixação Interna de Fraturas/efeitos adversos , Fraturas por Compressão/etiologia , Resultado do Tratamento
7.
ACS Nano ; 17(8): 7456-7465, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37014733

RESUMO

Introducing magnetism to two-dimensional topological insulators is a central issue in the pursuit of magnetic topological materials in low dimensionality. By means of low-temperature growth at 80 K, we succeeded in fabricating a monolayer stanene on Co/Cu(111) and resolving ferromagnetic spin contrast by field-dependent spin-polarized scanning tunneling microscopy (SP-STM). Increases of both remanence to saturation magnetization ratio (Mr/Ms) and coercive field (Hc) due to an enhanced perpendicular magnetic anisotropy (PMA) are further identified by out-of-plane magneto-optical Kerr effect (MOKE). In addition to ultraflat stanene fully relaxed on bilayer Co/Cu(111) from density functional theory (DFT), characteristic topological properties including an in-plane s-p band inversion and a spin-orbit coupling (SOC) induced gap about 0.25 eV at the Γ̅ point have also been verified in the Sn-projected band structure. Interfacial coupling of single-atomic-layer stanene with ferromagnetic Co biatomic layers allows topological band features to coexist with ferromagnetism, facilitating a conceptual design of atomically thin magnetic topological heterostructures.

8.
Curr Drug Deliv ; 20(9): 1337-1350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35713141

RESUMO

BACKGROUND: Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers for drug delivery. MSNs have been widely used in pharmaceutical research as drug carriers because of their large pore volume, high surface area, excellent biocompatibility, nontoxicity, ease to functionalize, and sustained release effects. MSNs have attracted much attention during drug delivery because of their special structure. OBJECTIVE: The present study aimed to synthesize mesoporous silica nanoparticles (MSNs), dendritic mesoporous silica nanoparticles (DMSN), and hollow mesoporous silica nanoparticles (HMSN) through facile methods, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug. METHODS: MSN, DMSN, and HMSN were characterized by SEM, TEM, FT-IR, nitrogen adsorptiondesorption isotherms, XRD, and zeta potential methods. Subsequently, puerarin (PUE) was used as the active ingredient and loaded into the three mesoporous materials, respectively. And, the drug delivery behavior was measured in PBS solution with different pH values. The sustained-release properties of MSN, DMSN, and HMSN loaded with PUE were investigated. Finally, the biocompatibility and stability of MSN, DMSN, and HMSN were studied by MTT assay and hemolysis assay. RESULTS: Our results showed that MSN, DMSN, and HMSN were successfully synthesized and the three types of mesoporous silica nanoparticles had higher drug loading and encapsulation efficiency. According to the first-order release equation curve and Higuchi equation parameters, the results showed that the PUE-loaded MSN, DMSN, and HMSN exhibited sustained-release properties. Finally, MTT and hemolysis methods displayed that MSN, DMSN, and HMSN had good biocompatibility and stability. CONCLUSION: In this study, MSN, DMSN, and HMSN were successfully synthesized, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug, we provided a theoretical and practical basis for the application of PUE.


Assuntos
Neuropatia Hereditária Motora e Sensorial , Nanopartículas , Humanos , Portadores de Fármacos/química , Preparações de Ação Retardada/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Hemólise , Microesferas , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Liberação Controlada de Fármacos , Porosidade
9.
J Clin Med ; 11(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36498666

RESUMO

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.

10.
Polymers (Basel) ; 13(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34451138

RESUMO

A series of hybrid fiber-reinforced composites were prepared with polyimide fiber and carbon fiber as the reinforcement and epoxy resin as the matrix. The influence of stacking sequence on the Charpy impact and flexural properties of the composites as well as the failure modes were studied. The results showed that hybrid fiber-reinforced composites yielded nearly 50% increment in Charpy impact strength compared with the ones reinforced by carbon fiber. The flexural performance was significantly improved compared with those reinforced solely by polyimide fibers and was greatly affected by the stacking sequence. The specimens with compressive sides distributed with carbon fiber possessed higher flexural strength, while those holding a sandwich-like structure with carbon fiber filling between the outer layers displayed a higher flexural modulus.

11.
Injury ; 52(6): 1287-1293, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33827774

RESUMO

BACKGROUND: The present study aimed to investigate the effects of mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 on ankylosing spondylitis and its underlying mechanisms. METHODS: Proteoglycan induced ankylosing spondylitis (PGIA) mouse model was established and the expression patterns of MALT-1 were determined in joint tissue. Next, the mice were intraarticularly administrated with MALT-1 in the PGIA mouse model. Meanwhile, shRNA was intraarticularly administrated to PGIA mice. The incidence of arthritis and clinical score was evaluated. Besides, the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) were measured. Protein expressions of full-length CYLD (FL-CYLD), C-terminal cleavage fragment (CYLD-CL), and nuclear factor (NF)-κB were determined. RESULTS: The mRNA and protein levels of MALT1 were increased in the PGIA mouse model. The treatment of MALT-1 accelerated arthritis incidence and joint damage, whereas shMALT-1 suppressed arthritis symptoms in the PGIA mouse model. In addition, treatment of shMALT-1 suppressed the levels of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß), MMP-3, and MMP-9. Furthermore, the treatment of shMALT-1 suppressed the levels of CYLD and NF-κB in the joint tissues in the PGIA mouse model. CONCLUSION: The inhibition of MALT-1 suppressed the inflammatory response in ankylosing spondylitis in part by the regulation of CYLD and NF-κB.


Assuntos
NF-kappa B , Espondilite Anquilosante , Animais , Citocinas , Interleucina-6 , Camundongos , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/antagonistas & inibidores , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa
12.
J Orthop Surg Res ; 16(1): 65, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468187

RESUMO

BACKGROUND: Percutaneous kyphoplasty is the main method in the treatment of thoracolumbar osteoporotic compression fractures. However, much radiation exposure during the operation harms the health of surgeons and patients. In addition, the accuracy of this surgery still needs to be improved. This study aimed to assess the radiation exposure and clinical efficacy of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture. METHODS: Included in this retrospective cohort study were 60 patients (60-90 years) who had undergone unilateral vertebroplasty for thoracolumbar osteoporotic compression fracture at our hospital between June 2019 and June 2020. All showed no systemic diseases and were assigned to Tirobot group (treated with Tirobot-assisted approach) and control group (treated with traditional approach). Fluoroscopic frequency, operative duration, length of stay (LOS), post-operative complications (cement leakage, infection, and thrombosis), and pre-operative and pre-discharge indexes (VAS score, JOA score, and Cobb's angle) were compared. RESULTS: The fluoroscopic frequency (P < 0.001) and post-operative complications (P = 0.035) in Tirobot group were significantly lower than those in control group. The operative duration and LOS in the Tirobot group were shorter than those in the control group, but the differences were not statistically significant (P = 0.183). Pre-discharge VAS score and Cobb's angle decreased, and JOA increased after surgeries in both groups. These three indexes showed a significant difference after surgery in each group (P < 0.001), but not between groups (PVAS = 0.175, PCobb's = 0.585, PJOA = 0.448). CONCLUSION: The Tirobot-assisted vertebroplasty can reduce surgery-related trauma, post-operative complications, and patients' and operators' exposure to radiation. As a safe and effective strategy, this surgery can realize the quick recovery from thoracolumbar osteoporotic compression fracture.


Assuntos
Fraturas por Compressão/cirurgia , Vértebras Lombares/cirurgia , Fraturas por Osteoporose/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Vértebras Torácicas/cirurgia , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoroscopia/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Exposição à Radiação/prevenção & controle , Exposição à Radiação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
13.
J Biomed Res ; 34(5): 379-386, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32934191

RESUMO

Thoracolumbar fractures are usually treated by open posterior pedicle screw fixation. However, this procedure involves massive paraspinal muscle stripping, inflicting surgical trauma, and prolonged X-ray exposure. In this study, we observed 127 patients with single-segment injury thoracolumbar fractures. Thirty-six patients were treated by the modified Wiltse's paraspinal approach with minimally invasive channel system, while 91 patients were treated via traditional posterior approach. Operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, screw placement accuracy, visual analogue scale score, and Cobb's angle of two groups were compared. The X-ray exposure times were notably reduced (4.2±1.6) in the new approach group (P<0.05). The pedicle screw placement accuracy and Cobb's angle after surgery were similar in the two groups. We conclude that modified Wiltse's paraspinal approach with spinal minimally invasive channel system surgery can significantly reduce the X-ray exposure times and is an alternative therapy for the thoracolumbar fracture.

14.
ACS Nano ; 7(2): 1333-41, 2013 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-23273110

RESUMO

Band gap opening and engineering is one of the high priority goals in the development of graphene electronics. Here, we report on the opening and scaling of band gap in BN doped graphene (BNG) films grown by low-pressure chemical vapor deposition method. High resolution transmission electron microscopy is employed to resolve the graphene and h-BN domain formation in great detail. X-ray photoelectron, micro-Raman, and UV-vis spectroscopy studies revealed a distinct structural and phase evolution in BNG films at low BN concentration. Synchrotron radiation based XAS-XES measurements concluded a gap opening in BNG films, which is also confirmed by field effect transistor measurements. For the first time, a significant band gap as high as 600 meV is observed for low BN concentrations and is attributed to the opening of the π-π* band gap of graphene due to isoelectronic BN doping. As-grown films exhibit structural evolution from homogeneously dispersed small BN clusters to large sized BN domains with embedded diminutive graphene domains. The evolution is described in terms of competitive growth among h-BN and graphene domains with increasing BN concentration. The present results pave way for the development of band gap engineered BN doped graphene-based devices.

15.
Phys Rev Lett ; 110(11): 117203, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25166570

RESUMO

Interfacial moments of an antiferromagnet are known for their prominent effects of induced coercivity enhancement and exchange bias in ferromagnetic-antiferromagnetic exchange-coupled systems. Here we report that the unpinned moments of an antiferromagnetic face-centered-cubic Mn layer can drive the magnetization of an adjacent Fe film perpendicular owing to a formation of intrinsic perpendicular anisotropy. X-ray magnetic circular dichroism and hysteresis loops show establishment of perpendicular magnetization on Fe/Mn bilayers while temperature was decreased. The fact that the magnitude of perpendicular anisotropy of the Fe layer is enhanced proportionally to the out-of-plane oriented orbital moment of the Mn unpinned layer, rather than that of Fe itself, gives evidence for the Mn unpinned moments to be the origin of the established perpendicular magnetization.

16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 27(4): 842-6, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20842856

RESUMO

This study was conducted to isolate and purify antimicrobial polypeptides HMGN2 (high mobility group nucleosomal-binding domain2) from human lymph node, to detect the antimicrobial activity of HMGN2, and to determine the subcellular location of HMGN2 in human lymph node. The antimicrobial polypeptides were purified by the Reverse Phase HPLC and identified by Tricine-SDS-PAGE. The antimicrobial activity was detected by agar diffusion test. Mass spectrum and Western-blot analysis indicated the individual character of protein. HMGN2 was isolated and purified from human lymph node, and it showed antimicrobial potency against the pathogenic strain E. coli 54,080. The immunocytochemistry staining indicated that HMGN2 was present both in human lymph node cells' nucleus and cytoplasm. In conclusion, HMGN2 protein is of antimicrobial activity and it is probably involved in the defence of innate immunity in vivo.


Assuntos
Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Proteína HMGN2/isolamento & purificação , Proteína HMGN2/metabolismo , Linfonodos/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Escherichia coli/efeitos dos fármacos , Humanos , Linfonodos/química , Distribuição Tecidual
17.
Antiviral Res ; 81(3): 277-82, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19150374

RESUMO

Natural killer (NK) cells and cytolytic T lymphocytes (CTL) have been implicated as important effectors of antiviral defense. We previously isolated a novel antibacterial polypeptide, which was identified as high mobility group nucleosomal-binding domain 2 (HMGN2), from human mononuclear leukocytes. This study examined the antiviral activity of HMGN2 against human hepatitis virus B. HMGN2 was isolated and purified from the acid soluble proteins of the human THP-1 cell line, and identified by mass spectrum, Western blot and antibacterial assay. The hepatitis B virus (HBV)-transfected HepG2.2.15 cell line was used in the in vitro assay system. In the range of 1-100 microg/ml HMGN2, no cytotoxicity for HepG2.2.15 cells was detected by MTT assay. When incubated with HMGN2 at 1-100 microg/ml for 72 or 144 h, there was a significant reduction in hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) expression, which were detected by ELISA, and a significant reduction in HBV DNA copies, which was determined by the real time quantitative PCR, in the supernatant of HepG2.2.15 cells. Northern and Southern blot analysis also showed that the levels of the HBV 3.5 kb and the 2.4/2.1 kb mRNA species and HBV replicative intermediate DNA were significantly reduced in the HMGN2-treated HepG2.2.15 cells. These results indicated that HMGN2 protein could markedly inhibit HBV protein expression and replication in vitro.


Assuntos
Regulação Viral da Expressão Gênica/efeitos dos fármacos , Proteína HMGN2/isolamento & purificação , Proteína HMGN2/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Hepatócitos/virologia , Replicação Viral/efeitos dos fármacos , Northern Blotting , Southern Blotting , Linhagem Celular , Sobrevivência Celular , DNA Viral/biossíntese , Ensaio de Imunoadsorção Enzimática/métodos , Proteína HMGN2/toxicidade , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos E da Hepatite B/biossíntese , Humanos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/biossíntese , RNA Viral/biossíntese
18.
Hum Reprod ; 24(1): 211-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18786935

RESUMO

BACKGROUND: Hemoglobin is a precursor of antibacterial peptides. Our aim was to identify an antibacterial peptide in human endometrium. We tested the antimicrobial activities of hemoglobin and a derived peptide in vitro and in vivo in rats. METHODS: Samples (n = 3) were scraped from the surface of endometrium. Acid-soluble proteins underwent electrophoresis followed by gel overlay assay and reversed-phase high-performance liquid chromatography. Antibacterial activities were determined by agar radial diffusion assay. Purified peptides were further characterized by electrophoresis, mass spectrometry, N-terminal amino acid (AA) sequencing and protein structure analysis. A rat model was used to test the inhibitory activity of human hemoglobin on vaginal infection with Escherichia coli, using one experimental group (intravaginal hemoglobin, n = 9) and three control groups (n = 14). Vaginal histology was studied. RESULTS: The purified peptide exhibited potent antibacterial activities against E. coli ML-35P. The N-terminal AA sequence was F L S F P T T K T Y, identical to AA 32-41 of the human hemoglobin alpha chain, and it had the same mass (m/z = 6776.8) as the alpha chain 32-93 AA fragment, with at least three alpha-helices. Histology indicated that the hemoglobin group changed significantly compared with the matrix control group (no treatment after infection): the surface layer of stratified squamous epithelium was smoother, inflammatory cell infiltration was relieved in the lamina propria and congestion pattern was decreased. CONCLUSIONS: These results suggest that erythrocytes from endometrium are another source of the antimicrobial molecules. Hemoglobin and its derived peptides may play a role in the host defense against pathogens in human vagina.


Assuntos
Antibacterianos/farmacologia , Hemoglobinas/farmacologia , Vagina/microbiologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Endométrio/metabolismo , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Ciclo Estral , Feminino , Hemoglobinas/química , Hemoglobinas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Útero/patologia , Vagina/metabolismo , Vagina/patologia
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 38(3): 404-7, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17593817

RESUMO

OBJECTIVE: To test the function of BCG cell wall proteins in enhancing the clearance of Pseudomonas aeruginosa in rat lungs. METHODS: The BCG cells were broken by supersonic technique. The cell wall proteins were isolated by discontinues sucrose density-gradient centrifugation, and fractionated by Sephadex G-150 chromatography. The relative molecular mass of the isolated proteins was analyzed by SDS-PAGE. The hBD-1 gene mRNA expression in the SPC-A-1 cells was identified by Northern blot and RT-PCR. The cell wall component was injected intraperitoneally to the rats. Forty eight hours later, 5 X 10(6) CFU of P. aeruginosa ATCC27853 or Staphylococcus aureus ATCC25923 were inoculated via trachea. The bacteria colony in the supernatant of the homogenated lungs of the rats was counted 24 hours after the inoculation. RESULTS: Two protein components of BCG cell wall were fractionated. The relative molecular mass of component 2 was in the range of 18 X 10(3) -30 X 10(3). The hBD-1 mRNA expression detected by Northern blot was markedly enhanced by the stimulation of heat-inactivated BCG whole cells. The BCG-induced hBD-1 mRNA expression in the SPC-A-1 cells detected by RT-PCR was mainly contributed by fraction 2 of the BCG cell wall proteins. The bacteria decreased significantly in the lungs of the rats with the injection of BCG component 2 (n=8, P<0. 01). CONCLUSION: The fraction (relative molecular mass is 18 X 10(3) -30 X 10(3)) of BCG cell wall proteins improve the defense of rat lungs against P. aeruginosa infection.


Assuntos
Proteínas de Bactérias/imunologia , Parede Celular/química , Pulmão/metabolismo , Pulmão/microbiologia , Mycobacterium bovis/citologia , Pseudomonas aeruginosa/fisiologia , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Defensinas/genética , Regulação da Expressão Gênica/imunologia , Pulmão/imunologia , Masculino , Peso Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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