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1.
Pharmaceutics ; 16(6)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38931937

ABSTRACT

Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this study, novel pharmaceutical cocrystals of PROG were successfully prepared by solvent evaporation or a liquid-assisted grinding process aimed at enhancing its solubility and bioavailability. The cocrystal formers selected based on crystal engineering principles were carboxylic acids, namely, 4-formylbenzeneboronic acid (BBA), isophthalic acid (IPA), and 3-nitrophthalic acid (NPA). The cocrystal structures were characterized using multiple techniques. Single-crystal X-ray diffraction results showed that the carbonyl group, acting as a hydrogen bond acceptor, was pivotal in the cocrystal network formation, with C-H···O interactions further stabilizing the crystals. The cocrystals exhibited improved solubility and dissolution profiles in vitro, with no significant changes in hygroscopicity. The parallel artificial membrane permeability assay (PAMPA) models indicated that the cocrystals retained PROG's high permeability. Pharmacokinetic studies in Sprague-Dawley rats revealed that all cocrystals increased PROG exposure, with AUC(0~∞) values for PROG-BBA, PROG-IPA, and PROG-NPA being 742.59, 1201.72 and 442.67 h·ng·mL-1, respectively. These values are substantially higher compared to free PROG, which had an AUC(0~∞) of 301.48 h·ng·mL-1. Notably, PROG-IPA provided the highest AUC improvement, indicating a significant enhancement in bioavailability. Collectively, the study concludes that the cocrystal approach is a valuable strategy for optimizing the physicochemical properties and oral bioavailability of PROG, with potential implications for the development of other poor water-soluble drugs.

2.
ACS Appl Bio Mater ; 7(5): 3202-3214, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38651918

ABSTRACT

The combination of small-interfering RNA (siRNA)-mediated gene silencing and chemotherapeutic agents for lung cancer treatment has attracted widespread attention in terms of a greater therapeutic effect, minimization of systemic toxicity, and inhibition of multiple drug resistance (MDR). In this work, three amphiphiles, CBN1-CBN3, were first designed and synthesized as a camptothecin (CPT) conjugate and gene condensation agents by the combination of CPT prodrugs and di(triazole-[12]aneN3) through the ROS-responsive phenylborate ester and different lengths of alkyl chains (with 6, 9, 12 carbon chains for CBN1-CBN3, respectively). CBN1-CBN3 were able to be self-assembled into liposomes with an average diameter in the range of 320-240 nm, showing the ability to effectively condense siRNA. Among them, CBN2, with a nine-carbon alkyl chain, displayed the best anticancer efficiency in A549 cells. In order to give nanomedicines a stealth property and PEGylation/dePEGylation transition, a GSH-responsive PEGylated TPE derivative containing a disulfide linkage (TSP) was further designed and prepared. A combination of CBN2/siRNA complexes and DOPE with TSP resulted in GSH/ROS dual-responsive lipid-polymer hybrid nanoparticles (CBN2-DP/siRNA NPs). In present GSH and H2O2, CBN2-DP/siRNA NPs were decomposed, resulting in the controlled release of CPT drug and siRNA. In vitro, CBN2-DP/siPHB1 NPs showed the best anticancer activity for suppression of about 75% of A549 cell proliferation in a serum medium. The stability of CBN2-DP/siRNA NPs was significantly prolonged in blood circulation, and they showed effective accumulation in the A549 tumor site through an enhanced permeability and retention (EPR) effect. In vivo, CBN2-DP/siPHB1 NPs demonstrated enhanced synergistic cancer therapy efficacy and tumor inhibition as high as 71.2%. This work provided a strategy for preparing lipid-polymer hybrid NPs with GSH/ROS dual-responsive properties and an intriguing method for lung cancer therapy.


Subject(s)
Biocompatible Materials , Camptothecin , Cell Proliferation , Drug Screening Assays, Antitumor , Lung Neoplasms , Nanoparticles , RNA, Small Interfering , Reactive Oxygen Species , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , RNA, Small Interfering/chemistry , Camptothecin/chemistry , Camptothecin/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Cell Proliferation/drug effects , Materials Testing , Glutathione/chemistry , Glutathione/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , A549 Cells , Particle Size , Lipids/chemistry , Molecular Structure , Animals , Cell Survival/drug effects , Mice , Prohibitins
3.
Int J Biol Macromol ; 256(Pt 1): 128345, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38007011

ABSTRACT

Aerogels as drug carriers have the characteristics of a large specific surface area, high porosity and an elastic skeleton structure. Compared with traditional drug carriers, the use of aerogels as drug carriers can avoid the complexity of drug delivery and improve the efficiency of drug loading. In this work, the oxidation of tunicate cellulose nanocrystals (tCNCs) with NaIO4 was used to prepare di-aldehyde tunicate cellulose nanocrystals (D-tCNCs). Tetracycline (TC) was used as a drug model and pH-responsive drug-loaded aerogels were prepared by the Schiff base reaction between TC and the aldehyde group on D-tCNCs. The chemical structure, crystallinity, morphology, compression properties, porosity, swelling rate and drug loading properties were investigated by FT-IR, XRD, SEM and universal testing machines. The results showed that the porosity and equilibrium swelling ratio of the D-tCNC-TC aerogels were 95.87 % and 17.52 g/g, respectively. The stress of the D-tCNC-TC aerogel at 15 % compression was 0.07 MPa. Moreover, the analysis of drug-loaded aerogels indicated that the drug loading and encapsulation rates of D-tCNC-TC aerogels were 16.86 % and 78.75 %, respectively. In in vitro release experiments, the cumulative release rate of drug-loaded aerogel at pH = 1.2 and pH = 7.4 was 87.5 % and 79.3 %, respectively. These results indicated that D-tCNC-TC aerogels have good drug loading capacity and are pH-responsive in the pH range of 1.2 to 7.4. The prepared D-tCNC-TC aerogels are expected to be applied in drug delivery systems.


Subject(s)
Nanoparticles , Urochordata , Animals , Cellulose/chemistry , Spectroscopy, Fourier Transform Infrared , Drug Delivery Systems , Drug Carriers/chemistry , Nanoparticles/chemistry , Gels/chemistry
4.
Int J Biol Macromol ; 242(Pt 3): 125010, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37217060

ABSTRACT

The highly conductive and elastic three-dimensional mesh porous material is an ideal platform for the fabrication of high electrical conductivity conductive aerogels. Herein, a multifunctional aerogel that is lightweight, highly conductive and stable sensing properties is reported. Tunicate nanocellulose (TCNCs) with a high aspect ratio, high Young's modulus, high crystallinity, good biocompatibility and biodegradability was used as the basic skeleton to prepare aerogel by freeze-drying technique. Alkali lignin (AL) was used as the raw material, polyethylene glycol diglycidyl ether (PEGDGE) was used as the cross-linking agent, and polyaniline (PANI) was used as the conductive polymer. Preparation of aerogels by freeze-drying technique, in situ synthesis of PANI, and construction of highly conductive aerogel from lignin/TCNCs. The structure, morphology and crystallinity of the aerogel were characterized by FT-IR, SEM, and XRD. The results show that the aerogel has good conductivity (as high as 5.41 S/m) and excellent sensing performance. When the aerogel was assembled as a supercapacitor, the maximum specific capacitance can reach 772 mF/cm2 at 1 mA/cm2 current density, and maximum power and energy density can reach 59.4 µWh/cm2 and 3600 µW/cm2, respectively. It is expected the aerogel can be applied in the field of wearable devices and electronic skin.


Subject(s)
Alkalies , Lignin , Spectroscopy, Fourier Transform Infrared , Electric Conductivity
5.
Bioconjug Chem ; 34(1): 248-256, 2023 01 18.
Article in English | MEDLINE | ID: mdl-36621834

ABSTRACT

Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 µM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX·HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.


Subject(s)
Micelles , Polyethylene Glycols , Humans , Polyethylene Glycols/chemistry , HeLa Cells , Esterases , Drug Carriers/chemistry , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Polymers/chemistry , Drug Delivery Systems , Hydrogen-Ion Concentration
6.
Int J Biol Macromol ; 226: 194-201, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36493924

ABSTRACT

This paper presents a binary reinforcement system of polyamide polyamine epichlorohydrin with nanocellulose (PAE-NC) for effectively modification of the reclaimed fibres for paper production, and based on the improvement of physical and mechanical properties of cellulosic fibres together with PAE-NC self-crosslinking networks, the strengthening mechanisms of recycled papers are examined. The PAE-NC binary system was applied directly to old corrugated container (OCC) and softwood bleached kraft pulp (SWBKP), and handsheets are prepared with varying amounts of PAE/NC/PAE-NC, namely 0.05, 0.1, 0.3, 0.5, 0.75, 1.0, 1.5, 2.0 wt% (dry pulp). The results showed that the studied additives improved the performance of recycled fibres, whether SWBKP or OCC pulp, and handsheets in solely or combined mechanisms except for the air permeability of the handsheets. The treatment of PAE-NC combination was significantly more effective than those of PAE or NC alone for both OCC and SWBKP, although the combined PAE-NC treatment results in better performance enhancement for OCC than SWBKP handsheets, and the NC alone is more effective than PAE for SWBKP recycled paper and conversely for OCC recycled paper. SEM observations further confirmed that the combined PAE-NC addition treatment imparted a relatively uniform surface structure to the handsheet.


Subject(s)
Epichlorohydrin , Nylons , Epichlorohydrin/chemistry , Carbohydrates , Paper
7.
Int J Biol Macromol ; 214: 77-90, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35691432

ABSTRACT

We developed a highly conductive and flexible, anti-freezing sulfonated lignin (SL)-containing polyacrylic acid (PAA) (SL-g-PAA-Ni) hydrogel, with a high concentration of NiCl2. Ni2+ contributes multi-functions to the preparation of the hydrogel and its final properties, such as fast polymerization reaction as a result of the presence of redox pairs of Ni3+/Ni2+ and hydroquinone/quinone, and anti-freezing properties of the hydrogel due to the salt effects of NiCl2 so that at -20 °C the hydrogel shows similar properties to those at the room temperature. Thanks to the effective coordinations of Ni2+ with catecholic groups and carboxylic groups, as well as the rich hydrogen bonding capacity, the resultant hydrogel possesses excellent mechanical properties. High ionic conductivity (6.85 S·m-1) of the hydrogel is obtained due to the supply of high concentration of Ni2+. Moreover, the ionic solvation effect of NiCl2 in the hydrogel imparts excellent water retention ability, with water retention of ~93 % after 21-day storage. The SL-g-PAA-Ni hydrogel can accurately detect various human motions at -20 °C. The supercapacitor assembled from SL-g-PAA-Al hydrogel at -20 °C manifests a high specific capacitance of 252 F·g-1, with maximum energy density of 26.97 Wh·kg-1, power density of 2667 W·kg-1, and capacitance retention of 96.7 % after 3000 consecutive charge-discharge cycles.


Subject(s)
Hydrogels , Lignin , Electric Conductivity , Humans , Polymerization , Water
8.
Int J Biol Macromol ; 207: 48-61, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35247419

ABSTRACT

Herein, we design a dynamic redox system of using high contents of lignosulfonate (LS) and Al3+ to prepare poly acrylic acid (PAA) (LS-g-PAA-Al) hydrogels. The presence of high LS and Al3+ contents, in combination with the effective Al3+ complexes formed, renders the resultant hydrogel with some unique attributes, including excellent ionic conductivity (as high as 7.38 S·m-1) and antibacterial activity; furthermore, a very fast gelation (in 1 min) was obtained. As a flexible strain sensor, the LS-g-PAA-Al hydrogel with high conductivity demonstrates superior sensitivity in human movement detection. In addition, the rich anionic hydrophilic groups, such as sulfonic groups, phenolic hydroxyl groups, in the hydrogels impart the resultant hydrogels with excellent adsorption capacity for cationic dyes: when using Rhodamine B (RB) as a model cationic dye, the adsorption capacity of the resultant hydrogel reaches 334.64 mg·g-1; as a moist-induced power generator, it generates maximum 150.5 mV open circuit voltage with moist air flow. When the hydrogel electrolyte is assembled into a supercapacitor assembly, it shows high specific capacitance of 245.4 F·g-1, with the maximum energy density of 21.8 Wh·kg-1, power density of 2.37 kW·kg-1, and capacitance retention of 95.1% after 5000 consecutive charge-discharge cycles.


Subject(s)
Hydrogels , Lignin , Anti-Bacterial Agents/pharmacology , Coloring Agents , Electric Conductivity , Humans
9.
Biomacromolecules ; 23(3): 766-778, 2022 03 14.
Article in English | MEDLINE | ID: mdl-35049296

ABSTRACT

Preparation of natural polymer-based highly conductive hydrogels with tunable mechanical properties for applications in flexible electronics is still challenging. Herein, we report a facile method to prepare lignin-based Fe3+-rich, high-conductivity hydrogels via the following two-step process: (1) lignin hydrogels are prepared by cross-linking sulfonated lignin with poly(ethylene glycol) diglycidyl ether (PEGDGE) and (2) Fe3+ ions are impregnated into the lignin hydrogel by simply soaking in FeCl3. Benefiting from Fe3+ ion complexation with catechol groups and other functional groups in lignin, the resultant hydrogels exhibit unique properties, such as high conductivity (as high as 6.69 S·m-1) and excellent mechanical and hydrophobic properties. As a strain sensor, the as-prepared lignin hydrogel shows high sensitivity when detecting various human motions. With the flow of moist air, the Fe3+-rich lignin hydrogel generates an output voltage of 162.8 mV. The assembled supercapacitor of the hydrogel electrolyte demonstrates a high specific capacitance of 301.8 F·g-1, with a maximum energy density of 26.73 Wh·kg-1, a power density of 2.38 kW·kg-1, and a capacitance retention of 94.1% after 10 000 consecutive charge-discharge cycles. These results support the conclusion that lignin-based Fe3+-rich, high-conductivity hydrogels have promising applications in different fields, including sensors and supercapacitors, rendering a new platform for the value-added utilization of lignin.


Subject(s)
Hydrogels , Lignin , Electric Capacitance , Electric Conductivity , Humans , Hydrogels/chemistry , Ions , Lignin/chemistry , Polymers/chemistry
10.
Carbohydr Res ; 511: 108488, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34875481

ABSTRACT

First time aerogels composite with super hydrophobic properties were developed by using tunicate cellulose nanocrystals (TCNC), which expanded the application scope of animal cellulose resources. In this study, the TCNC was firstly cross-linked with silica and methyltrimethylsilane (MTMS), further coated with fluorodopa to form an aerogel with super hydrophobic properties. The aerogel was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), and X-ray photoelectron spectroscopy (XPS). Results indicated that the contact angle of aerogel was 158.7°, which showed good hydrophobicity. The composite aerogel has superior stability in wide pH range, after 72 h immersion in pH = 0 and 12 solutions, the contact angle was still greater than 150°. The aerogel shows excellent oil-water separation ability and it can be repeatedly used more than 10 times. The separation efficiency can all reach more than 90% for different water-oil mixtures. This synthesized super hydrophobic aerogels derived from tunicate cellulose has greatly extended the application of marine animal celluloses.


Subject(s)
Nanoparticles , Urochordata , Animals , Cellulose/chemistry , Gels/chemistry , Hydrophobic and Hydrophilic Interactions , Spectroscopy, Fourier Transform Infrared
11.
Bioorg Chem ; 119: 105559, 2022 02.
Article in English | MEDLINE | ID: mdl-34952244

ABSTRACT

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Delivery Systems , Hydrogen Peroxide/chemistry , Polymers/chemistry , Surface-Active Agents/chemistry , Animals , Antibiotics, Antineoplastic/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Liberation , Drug Screening Assays, Antitumor , Female , HEK293 Cells , HeLa Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Protein Aggregates , Structure-Activity Relationship
12.
Int J Biol Macromol ; 187: 189-199, 2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34265336

ABSTRACT

Lignin, an abundant natural polymer but presently under-utilized, has received much attention for its green/sustainable advantages. Herein, we report a facile method to fabricate lignosulfonate (LS) ionic hydrogels by simple crosslinking with poly (ethylene glycol) diglycidyl ether (PEGDGE). The as-obtained LS-PEGDGE hydrogels were comprehensively characterized by mechanical measurements, FT-IR, and SEM. The rich sulfonic and phenolic hydroxyl groups in LS hydrogels play key roles in imparting multifunctional smart properties, such as adhesiveness, conducting, sensing and dye adsorption, as well as superconductive behavior when increasing the moisture content. The hydrogels have a high adsorption capacity for cationic dyes, using methylene blue as a model, reaching 211 mg·g-1. As a moist-induced power generator, the maximum output voltage is 181 mV. The LS-PEGDGE hydrogel-based flexible strain sensors exhibit high sensitivity when detecting human movements. As the hydrogel electrolyte, the assembled supercapacitor shows high specific capacitance of 236.9 F·g-1, with the maximum energy density of 20.61 Wh·kg-1, power density of 2306.4 W·kg-1, and capacitance retention of 92.9% after 10,000 consecutive charge-discharge cycles. Therefore, this multifunctional LS hydrogels may have promising applications in various fields, providing a new platform for the value-added utilization of lignin from industrial waste.


Subject(s)
Coloring Agents/chemistry , Electric Capacitance , Epoxy Resins/chemistry , Hydrogels/chemistry , Lignin/analogs & derivatives , Methylene Blue/chemistry , Water Pollutants, Chemical/chemistry , Lignin/chemistry
13.
Polymers (Basel) ; 12(12)2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33371516

ABSTRACT

Tunicate is a kind of marine animal, and its outer sheath consists of almost pure Iß crystalline cellulose. Due to its high aspect ratio, tunicate cellulose has excellent physical properties. It draws extensive attention in the construction of robust functional materials. However, there is little research on its biological activity. In this study, cellulose enzymatic hydrolysis was conducted on tunicate cellulose. During the hydrolysis, the crystalline behaviors, i.e., crystallinity index (CrI), crystalline size and degree of polymerization (DP), were analyzed on the tunicate cellulose. As comparisons, similar hydrolyses were performed on cellulose samples with relatively low CrI, namely α-cellulose and amorphous cellulose. The results showed that the CrI of tunicate cellulose and α-cellulose was 93.9% and 70.9%, respectively; and after 96 h of hydrolysis, the crystallinity, crystalline size and DP remained constant on the tunicate cellulose, and the cellulose conversion rate was below 7.8%. While the crystalline structure of α-cellulose was significantly damaged and the cellulose conversion rate exceeded 83.8% at the end of 72 h hydrolysis, the amorphous cellulose was completely converted to glucose after 7 h hydrolysis, and the DP decreased about 27.9%. In addition, tunicate cellulose has high anti-mold abilities, owing to its highly crystalized Iß lattice. It can be concluded that tunicate cellulose has significant resistance to enzymatic hydrolysis and could be potentially applied as anti-biodegradation materials.

15.
Comput Biol Med ; 43(11): 1949-54, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24209940

ABSTRACT

Three-dimensional (3D) finite element models of a posterior mandibular segment and a distraction implant (DI) were created and assembled in this study. The diameter of distraction screw (DS) was set as input variable, ranging from 1.0 to 3.0mm, to analyze the stress and displacement, in order to obtain an optimal outcome of the DI. The results indicate that when the diameter of DS was 2.0mm, the stresses in jaw bone and DS and the displacement of DS reached a relatively low range. The diameter of DS significantly affects the stress distribution in DI and surrounding bone. The present study demonstrates that from clinical and biomechanical points of view, the optimal diameter of DS is 2.0mm.


Subject(s)
Biomechanical Phenomena/physiology , Computer-Aided Design , Dental Implants , Dental Prosthesis Design/methods , Bone Screws , Finite Element Analysis , Humans , Mandible/physiology , Models, Dental
16.
Biochem Biophys Res Commun ; 442(1-2): 8-15, 2013 Dec 06.
Article in English | MEDLINE | ID: mdl-24211590

ABSTRACT

Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Autophagy , Cardiomegaly/pathology , Cold Temperature , Cold-Shock Response , Muscle Contraction , TRPV Cation Channels/metabolism , Animals , Cardiomegaly/metabolism , Echocardiography , Male , Membrane Potential, Mitochondrial , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/metabolism , Reactive Oxygen Species/metabolism , TOR Serine-Threonine Kinases/metabolism , TRPV Cation Channels/genetics
17.
PLoS One ; 8(8): e70768, 2013.
Article in English | MEDLINE | ID: mdl-23951004

ABSTRACT

OBJECTIVE: To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey. METHODS: 186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed. RESULTS: 1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region. CONCLUSIONS: Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.


Subject(s)
Hepatitis B virus , Hepatitis B/epidemiology , Child, Preschool , China , DNA, Viral/genetics , Female , Genome, Viral , Hepatitis B/virology , Hepatitis B Antibodies/immunology , Hepatitis B Surface Antigens/genetics , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Humans , Incidence , Infant , Infant, Newborn , Male , Mothers , Mutation , Phylogeny , Prevalence , Viral Load
18.
Am J Trop Med Hyg ; 87(4): 646-54, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22869636

ABSTRACT

Hainan Province is the main area threatened by malaria in China. However, the epidemiologic patterns of malaria in this region are not yet defined. In this study, we determined the spatio-temporal distribution and variation of Plasmodium falciparum and Plasmodium vivax malaria in Hainan during 1995-2008 by using wavelet and cluster quantitative approaches. The results indicated a decreasing secular trend and obvious seasonal fluctuation of malaria in Hainan. In addition, the characteristic annual peak of malaria could not be detected after 2005. The south-central region of Hainan has remained an area of relatively high malaria risk, but the incidence of P. falciparum malaria increased significantly in the southeast and southwest regions during 2002-2008. These findings identify epidemic patterns of malaria in Hainan, and are applicable for designing an effective and dynamic public health campaign to combat malaria in this region.


Subject(s)
Epidemics , Malaria, Falciparum/epidemiology , Malaria, Vivax/epidemiology , Plasmodium falciparum/genetics , Plasmodium vivax/genetics , Seasons , China/epidemiology , Humans , Incidence , Malaria, Falciparum/parasitology , Malaria, Vivax/parasitology , Plasmodium falciparum/isolation & purification , Plasmodium vivax/isolation & purification
19.
Hum Reprod ; 26(8): 2146-56, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21596708

ABSTRACT

BACKGROUND: Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. METHODS: Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. RESULTS: We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. CONCLUSIONS: We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.


Subject(s)
Hepatitis B virus/genetics , Trophoblasts/cytology , Cell Line , Clone Cells , Female , Humans , Pregnancy , Pregnancy Trimester, First , Transfection , Trophoblasts/metabolism , Trophoblasts/virology
20.
J Med Virol ; 83(5): 791-5, 2011 May.
Article in English | MEDLINE | ID: mdl-21360547

ABSTRACT

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine.


Subject(s)
Hepatitis B virus/isolation & purification , Hepatitis B/epidemiology , Hepatitis B/transmission , Infectious Disease Transmission, Vertical/prevention & control , Adult , Asian People , Carrier State/epidemiology , Carrier State/prevention & control , China/epidemiology , Female , Follow-Up Studies , Hepatitis B/prevention & control , Hepatitis B/virology , Hepatitis B Antibodies/administration & dosage , Hepatitis B Vaccines/administration & dosage , Humans , Infant, Newborn , Male , Mothers , Pregnancy , Prospective Studies , Treatment Outcome
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