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1.
Huan Jing Ke Xue ; 45(2): 813-825, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471920

ABSTRACT

Chaohu lake is a key water body for water pollution prevention and treatment in our country. However, it has been at a higher eutrophication level recently. Here, the surface water and groundwater in the Dianbu River Basin, a secondary tributary of Chaohu Lake, were taken as the research object. In order to test the hydrochemical composition and hydrogen and oxygen isotope values of different water bodies, 30 groups of surface water samples, 36 groups of groundwater samples, 16 groups of hydrogen and oxygen stable isotope samples, and 18 groups of groundwater hydrogen and oxygen stable isotope samples were collected in August 2021 (wet season), November 2021 (normal season), and February 2022 (dry season). The seasonal and spatial variation characteristics were analyzed to explore the hydrochemical characteristics and formation mechanism of water bodies by means of mathematical statistics, Piper triangular diagram, Gibbs figures, and ion ratios. The following results were obtained: ① precipitation was the main source of surface water and groundwater in Dianbu River Basin, and the evaporation fractionation effect of surface water was more significant than that of groundwater. At different periods, the surface water was more enriched with stable isotopes of hydrogen and oxygen than groundwater. The stable isotopes of hydrogen and oxygen in water showed seasonal variation, relative enrichment in the wet season, and depletion in the dry season. ② Both surface water and groundwater in the Dianbu River Basin were weakly alkaline, and the concentration of ions in surface water was significantly lower than that in groundwater. Ca2+ and Na+ were the main cations in surface water, Ca2+ was the main cation in groundwater, and the dominant anion in all water was HCO3-. The hydrochemical typology of surface water was mainly HCO3·Cl-Na·Ca, and that of groundwater was mainly HCO3-Na·Ca. ③ The concentrations of the main hydrochemical indexes of surface water and groundwater showed certain seasonal and spatial differences. From the wet season to the dry season, the concentrations of TDS, K+, Na+, Ca2+, Mg2+, Cl-, and SO42- in surface water showed an increasing trend on the whole. The concentrations of Na+, Ca2+, and Mg2+ in groundwater showed little change but increased slightly, whereas the concentrations of Cl-, SO42-, and NO3- showed an increasing trend on the whole. The concentrations of Cl-, SO42-, and NO3- in the water showed relatively large seasonal fluctuations. From upstream to downstream, the concentrations of the main hydrochemical indexes in surface water first decreased and then increased, among which the concentration of NO3- increased the most. The concentrations of the main hydrochemical indexes of groundwater in the direction of runoff changed little overall, but the concentration in the discharge area was higher than that in the recharge area. ④ The formation of hydrochemical characteristics of the water was mainly controlled by water-rock interaction but was also influenced by human factors. The water-rock action was mainly the weathering dissolution of silicate rock, salt rock, and carbonate rock. Man-made pollutants such as sewage from a sewage treatment plant, domestic sewage, and feces had obviously changed the hydrochemical characteristics of the local water. ⑤ Compared with that in 2016, the concentration of NO3- in surface water showed a certain degree of reduction. The nitrogen pollution control work carried out by the local government had achieved certain results, but it was still necessary to strengthen the pollution prevention and control of sewage and feces in the downstream of the Dianbu River, some tributaries (such as the Dingguang River and Maqiao River), and some residential areas.

2.
Ecotoxicol Environ Saf ; 269: 115788, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38056118

ABSTRACT

The contamination of arable land with heavy metals, such as Cd, is a serious concern worldwide. Intercropping with Cd accumulators can be used for efficient safe crop production and phytoremediation of Cd-contaminated soil. However, the effect of intercropping on Cd uptake by main crops and accumulators varies among plant combinations. Rhizosphere interaction may mediate Cd uptake by intercropped plants, but the mechanism is unclear. Thus, in the present study, we aimed to examine the effect of rhizosphere interaction on Cd uptake by intercropping rice (Oryza sativa L.) with mugwort (Artemisia argyi Levl. et Vant.) in Cd-contaminated paddy soil. We grew O. sativa and A. argyi in pots designed to allow different levels of interaction: complete root interaction (no barrier), partial root interaction (nylon mesh barrier), and no root interaction (plastic film barrier). Our results indicated that both complete and partial root interaction increased the shoot and root mass of A. argyi, but did not decrease the shoot, root, and grain mass of O. sativa. Interspecific root interaction significantly increased the Cd content in the shoots, roots, and grains of O. sativa and the shoots of A. argyi. Increased content of total organic acids in the rhizosphere, which increased the content of available Cd, was a possible mechanism of increased Cd uptake in both plants under interspecific root interaction. Our findings demonstrate that an intercropping system can extract more Cd from contaminated soil than a monocropping system of either A. argyi or O. sativa. However, the intercropping system did not facilitate safe crop production because it substantially increased grain Cd content in O. sativa.


Subject(s)
Oryza , Soil Pollutants , Cadmium/analysis , Soil , Plant Roots/chemistry , Edible Grain/chemistry , Biodegradation, Environmental , Soil Pollutants/analysis
3.
ACS Appl Mater Interfaces ; 15(32): 38273-38284, 2023 Aug 16.
Article in English | MEDLINE | ID: mdl-37530040

ABSTRACT

Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.


Subject(s)
Colitis, Ulcerative , Humans , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Hydrogels/pharmacology , Hydrogels/therapeutic use , Reactive Oxygen Species , Intestinal Mucosa , Chondroitin Sulfates/therapeutic use , Disease Models, Animal
4.
J Contam Hydrol ; 253: 104127, 2023 02.
Article in English | MEDLINE | ID: mdl-36587423

ABSTRACT

Large deep lakes in plateau regions provide crucial ecosystem services but are susceptible to eutrophication due to their long water residence time. To date, the water quality of deep lakes has not received as much attention as that of shallow lakes owing to logistical challenges. This study investigated the seasonal variation and vertical distribution of phosphorus and related environmental variables in a large deep lake in the Yunnan Plateau, China (Fuxian Lake). Generally, the concentrations of total phosphorus (TP, R2 = 0.862), total dissolved phosphorus (TDP, R2 = 0.922), and dissolved inorganic phosphorus (DIP, R2 = 0.889) exhibited a linear increase with the greater water depth, whereas the pH and dissolved oxygen (DO) showed decreasing trends. The TP, TDP, and DIP values were 0.012, 0.006, and 0.004 mg/L, respectively, in surface waters (0.5 m depth), and increased to 0.074, 0.065, and 0.062 mg/L, respectively, at 140.0 m depth. The averaged over ordering method demonstrated that DO and air temperature accounted for a higher proportion of the explained variance of TP, TDP, and DIP in the shallow water layer (0.5-20.0 m). In contrast, DO and pH accounted for a higher proportion of the explained variance of TP, TDP, and DIP in deeper water layers (40.0-150.0 m). As a warm monomictic lake, the higher observed phosphorus concentrations in deeper water and sediment potentially pose a risk of future eutrophication in the Fuxian Lake. Our findings demonstrate that more efficient technical and management measures should be taken to reduce the external phosphorus load to Fuxian Lake, so that the load to and from the sediment will decrease eventually.


Subject(s)
Lakes , Phosphorus , Ecosystem , China , Eutrophication , DNA-Binding Proteins , Environmental Monitoring , Nitrogen/analysis
5.
Macromol Biosci ; 23(2): e2200349, 2023 02.
Article in English | MEDLINE | ID: mdl-36333912

ABSTRACT

Diabetic mellitus is one of the leading causes of chronic wounds and remains a challenging issue to be resolved. Herein, a hydrogel with conformal tissue adhesivity, skin-like conductivity, robust mechanical characteristics, as well as active antibacterial function is developed. In this hydrogel, silver nanoparticles decorated polypyrrole nanotubes (AgPPy) and cobalt ions (Co2+ ) are introduced into an in situ polymerized poly(acrylic acid) (PAA) and branched poly(ethylenimine) (PEI) network (PPCA hydrogel). The PPCA hydrogel provides active antibacterial function through synergic effects from protonated PEI and AgPPy nanotubes, with a tissue-like mechanical property (≈16.8 ± 4.5 kPa) and skin-like electrical conductivity (≈0.048 S m-1 ). The tensile and shear adhesive strength (≈15.88 and ≈12.76 kPa, respectively) of the PPCA hydrogel is about two- to threefold better than that of fibrin glue. In vitro studies show the PPCA hydrogel is highly effective against both gram-positive and gram-negative bacteria. In vivo results demonstrate that the PPCA hydrogel promotes diabetic wounds with accelerated healing, with notable inflammatory reduction and prominent angiogenesis regeneration. These results suggest the PPCA hydrogel provide a promising approach to promote diabetic wound healing.


Subject(s)
Diabetes Mellitus , Metal Nanoparticles , Adhesives , Hydrogels/pharmacology , Polymers/pharmacology , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria , Gram-Positive Bacteria , Pyrroles , Silver/pharmacology , Wound Healing , Electric Conductivity
6.
J Control Release ; 352: 700-711, 2022 12.
Article in English | MEDLINE | ID: mdl-36347402

ABSTRACT

The clearance of nanomedicine in inflamed joints has been accelerated due to the increased lymph angiogenesis and lymph flow in arthritic sites. To maximize the therapeutic efficacy for rheumatoid arthritis (RA), it is necessary to facilitate targeted delivery and extended drug retention in inflamed synovium simultaneously. In general, nanosized particles are more likely to achieve prolonged circulation and targeted delivery. While drug carriers with larger dimension might be more beneficial for extending drug retention. To balance the conflicting requirements, an inflammation-responsive shape transformable nanoparticle, comprised of amyloid ß-derived KLVFF peptide and polysialic acid (PSA), coupled with therapeutic agent dexamethasone (Dex) via an acid-sensitive linker, was fabricated and termed as Dex-KLVFF-PSA (DKPNPs). Under physiological condition, DKPNPs can keep stable nanosized morphology, and PSA shell could endow DKPNPs with long circulation and active targeting to arthritic sites. While in inflamed joints, acidic pH-triggered Dex dissociation or macrophages-induced specific binding with PSA would induce the re-assembly of DKPNPs from nanoparticles to nanofibers. Our results reveal that intravenously injected DKPNPs display prolonged in vivo circulation and preferential distribution in inflamed joints, where DKPNPs undergo shape transition to fibrous structures, leading to declined lymphatic clearance and prolonged efficacy. Overall, our dual-stimulus responsive transformable nanoparticle offers an intelligent solution to achieve enhanced therapeutic efficacy in RA.


Subject(s)
Arthritis, Rheumatoid , Nanoparticles , Humans , Amyloid beta-Peptides , Arthritis, Rheumatoid/drug therapy , Synovial Membrane , Nanoparticles/chemistry , Inflammation/drug therapy
7.
Acta Biomater ; 150: 324-336, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35840107

ABSTRACT

Delivering therapeutic agents efficiently to inflamed joints remains an intractable problem in rheumatoid arthritis (RA) treatment due to the complicated physiological barriers. Circulating monocytes could selectively migrate to inflamed sites and differentiate into resident macrophages to aggravate RA. Therefore, a drug carrier that can be specifically internalized by circulating monocytes and switch monocytes into anti-inflammatory phenotype when reaching inflamed sites, might bypass the in vivo physiological barriers and achieve efficient RA therapy. Herein, we design a dextran sulfate (DS) functionalized nanoparticle (ZDNP) to selectively deliver anti-inflammatory agent dexamethasone (Dex) to circulating monocytes via the scavenger receptors on monocytes. Monocytes engulfing drug-loaded ZDNP could subsequently home to arthritic joints and act as a "living drug depot" to combat RA. Results revealed that ZDNP could be preferentially internalized by circulating monocytes when intravenously administrated in vivo. In a rat arthritic model, we found that circulating monocytes remarkably facilitated drug distribution and retention in inflamed joints. Moreover, monocytes engulfing drug-loaded nanoparticles exhibited favorable anti-inflammatory ability and M2-biased differentiation. Our work offers a facile approach to achieve site-directed anti-inflammatory therapy by taking advantage of the inflammation-homing ability of circulating monocytes. STATEMENT OF SIGNIFICANCE: Circulating monocytes can migrate to inflamed sites and then differentiate into macrophages to aggravate arthritis. Therefore, a drug carrier that can be specifically internalized by circulating monocytes and switch monocytes into anti-inflammatory phenotype when reaching inflamed sites may achieve efficient arthritis therapy. Here, we designed a monocyte-targeting nanoparticle (ZDNP) to selectively deliver anti-inflammatory Dex to circulating monocytes. When injected intravenously, ZDNP was effectively internalized by circulating monocytes via a scavenger receptor and subsequently was transported to arthritic joints, where monocytes engulfing the drug-loaded nanoparticles could switch to an anti-inflammatory phenotype to inhibit arthritis progress. We provide detailed evidence about the in vivo fate of ZDNP and unravel how monocytes act as a "living drug depot" to achieve site-directed arthritis therapy.


Subject(s)
Arthritis, Rheumatoid , Animals , Arthritis, Rheumatoid/drug therapy , Drug Carriers/therapeutic use , Inflammation/drug therapy , Macrophages , Monocytes , Rats
8.
Asian J Pharm Sci ; 16(4): 483-493, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34703497

ABSTRACT

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2-26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2-26 peptides hinders their efficacy in vivo. In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l-ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn­glycero-3-phosphoethanolamine (DSPE-PEG2k) to encapsulate and deliver Ac2-26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2-26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.

9.
ACS Appl Mater Interfaces ; 13(39): 46270-46281, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34550685

ABSTRACT

Although immune checkpoint blockade (ICB) holds potential for the treatment of various tumors, a considerable proportion of patients show a limited response to ICB therapy due to the low immunogenicity of a variety of tumors. It has been shown that some chemotherapeutics can turn low-immunogenic tumors into immunogenic phenotypes by inducing a cascade of immune responses. In this paper, we synthesized an injectable micelle-incorporated hydrogel, which was able to sequentially release the chemotherapeutic gemcitabine (GEM) and the hydrophobic indoleamine 2, 3-dioxygenase inhibitor, d-1-methyltryptophan (d-1MT) at tumor sites. The hydrogel was formed via the thiol-ene click reaction between the thiolated chondroitin sulfate and the micelle formed by amphiphilic methacrylated Pluronic F127, in which hydrophobic d-1MT was encapsulated in the core of the F127 micelles and the hydrophilic GEM was dispersed in the hydrogel network. The successive release of chemotherapeutics and immune checkpoint inhibitors at tumor tissues will first promote the infiltration of cytotoxic T lymphocytes and subsequently induce a robust antitumor immune response, ultimately exerting a synergetic therapeutic efficacy. In a 4T1 tumor-bearing mice model, our results showed that the combination of chemotherapy and immunotherapy through the micelle-incorporated hydrogel triggered an effective antitumor immune response and inhibited tumor metastasis to the lung. Our results highlight the potential of the injectable micelle-incorporated hydrogel for the localized chemo-immunotherapy in the treatment of breast tumors.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Delayed-Action Preparations/chemistry , Hydrogels/chemistry , Micelles , Animals , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , CD8-Positive T-Lymphocytes/drug effects , Cell Line, Tumor , Chondroitin Sulfates/chemical synthesis , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/toxicity , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/toxicity , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Enzyme Inhibitors/therapeutic use , Female , Hydrogels/chemical synthesis , Hydrogels/toxicity , Immunotherapy , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Mice, Inbred BALB C , Neoplasm Metastasis/prevention & control , Poloxamer/analogs & derivatives , Poloxamer/toxicity , Tryptophan/analogs & derivatives , Tryptophan/therapeutic use , Tumor Microenvironment/drug effects , Gemcitabine
10.
Acta Pharm Sin B ; 11(5): 1158-1174, 2021 May.
Article in English | MEDLINE | ID: mdl-34094826

ABSTRACT

Increasing understanding of the pathogenesis of rheumatoid arthritis (RA) has remarkably promoted the development of effective therapeutic regimens of RA. Nevertheless, the inadequate response to current therapies in a proportion of patients, the systemic toxicity accompanied by long-term administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability, are still unsettled problems lying across the full remission of RA. So far, these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment. A variety of versatile nanocarriers with controllable physicochemical properties, tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment. This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance, pro-resolving therapy or regulating the immunometabolism for RA treatments.

11.
ACS Appl Mater Interfaces ; 13(18): 21076-21086, 2021 May 12.
Article in English | MEDLINE | ID: mdl-33913684

ABSTRACT

The nontargeted distribution and uncontrolled in vivo release of drugs impede their efficacy in the treatment of rheumatoid arthritis (RA). Delivering drugs to arthritic joints and releasing drugs on demand are a feasible solution to achieve the effective treatment of RA. In this paper, we report a facile method to assemble dual-stimuli responsive polymeric micelles from polyethylene glycol-phenylboric acid-triglycerol monostearate (PEG-PBA-TGMS, PPT) conjugates with the aim of delivering dexamethasone (Dex) to arthritic joints and controlling the release of Dex by inflammatory stimuli. We show that the release of Dex from the PPT micelles is accelerated in response to acidic pH and overexpressed matrix metalloproteinases. In an adjuvant-induced arthritis model, the PPT micelles preferentially accumulate in arthritic joints and show an excellent therapeutic efficacy after being intravenously administrated. Our results highlight the potential of the dual stimuli-responsive micelles as a promising therapeutic option for the effective treatment of inflammatory diseases.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Dexamethasone/administration & dosage , Drug Carriers , Glucocorticoids/administration & dosage , Micelles , Polymers/chemistry , Animals , Biocompatible Materials , Dexamethasone/pharmacokinetics , Dexamethasone/therapeutic use , Drug Liberation , Glucocorticoids/pharmacokinetics , Glucocorticoids/therapeutic use , Hemolysis/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Mice , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Tissue Distribution
12.
J Biomed Nanotechnol ; 17(3): 357-368, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33875071

ABSTRACT

Ferulic acid (FA), an active component extracted from Chinese medicine, shows excellent anti-inflammatory properties and favorable safety in various animal models. However, the application of FA as an anti-inflammatory drug is hindered by its instability and short half-life in vivo . In this paper, we synthesize PEGylated diphenylalanine nanoparticles by using glutaraldehyde (GTA) as a cross-linker of diphenylalanine NH2 -Phe-Phe-COOH and poly(ethylene glycol) methyl ether amine (PEG5k -NH2). The PEGylated Phe-Phe nanoparticles are used to deliver FA for the treatment of Rheumatoid arthritis (RA). We find that the FA-loaded PEGylated Phe-Phe nanoparticles are biocompatible and inhibit the production of reactive oxygen species (ROS) from cells effectively. After being intravenously administrated in vivo , the FA-loaded PEGylated Phe-Phe nanoparticles show prolonged circulation time and accumulate in arthritic joints. More importantly, we show that the pre-arthritis treatment with the FA-loaded PEGylated Phe-Phe nanoparticles can significantly block the progression of RA.


Subject(s)
Folic Acid , Nanoparticles , Animals , Coumaric Acids , Drug Delivery Systems , Polyethylene Glycols
13.
Acta Pharm Sin B ; 11(3): 835-847, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33777685

ABSTRACT

Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform ("plum‒pudding" structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked via self-assembled triblock polymeric micelles ("plum") to help reduce renal interstitial fibrosis. This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice. Following a single injection, local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFß antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-κB signaling pathway or neutralizing TGF-ß1 locally. Importantly, the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity, which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis.

14.
ACS Appl Bio Mater ; 3(7): 3987-3991, 2020 Jul 20.
Article in English | MEDLINE | ID: mdl-35025473

ABSTRACT

An efficient strategy for noncovalent protein glycosylation has been developed by in situ saccharide-based nanoencapsulation. The positive monomer dimethylaminoethyl methacrylate is enriched on the protein surface via electrostatic adhesion, enabling free radical polymerization to generate nanocapsules with saccharides on the surface of the protein complex. Comparable to the glycosylation of native proteins, the d-fructose coated polymeric shell layer significantly enhanced the stability of proteins, rendering proteins with cell selectivity and tumor-specific distribution in MCF-7 breast tumor-bearing mice xenografts. Also, glycosylation improved the shelf life of therapeutic proteins which would further benefit manufacturing and facilitate transportation.

15.
Acta Pharmacol Sin ; 40(4): 514-521, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30002492

ABSTRACT

Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.


Subject(s)
Human Umbilical Vein Endothelial Cells/drug effects , Immunologic Factors/pharmacology , Phospholipids/chemistry , Thymopentin/chemistry , Animals , Cell Survival/drug effects , Cyclophosphamide , Delayed-Action Preparations , Drug Liberation , Female , Gels/chemistry , Gels/pharmacology , Humans , Immunologic Factors/chemistry , Immunosuppression Therapy , Mice , Phospholipids/pharmacology , Rats , Rats, Wistar , Viscosity
16.
Macromol Biosci ; 18(7): e1800047, 2018 07.
Article in English | MEDLINE | ID: mdl-29737012

ABSTRACT

An extracellular matrix-mimicking hydrogel is developed consisting of a hyaluronan-derived component with anti-inflammatory activity, and a gelatin-derived component offering adhesion sites for cell anchorage. The in situ-forming hyaluronan-gelatin (HA-GEL) hydrogel displays a sponge-like microporous morphology. Also, HA-GEL shows a rapid swelling pattern reaching maximum weight swelling ratio within 10 min, while at the equilibrium state, fully swollen hydrogels display an exceedingly high water content with ≈2000% of the dry gel weight. Under typical 2D cell culture conditions, murine 3T3 fibroblasts adhere to, and proliferate on top of the HA-GEL substrates, which demonstrate that HA-GEL provides a favorable microenvironment for cell survival, adhesion, and proliferation. In vivo healing study further demonstrates HA-GEL as a viable and effective treatment option to improve the healing outcome of full thickness wounds in diabetic mice by effectively depleting the inflammatory chemokine monocyte chemoattractant protein-1 in the wound bed.


Subject(s)
Biomimetic Materials/chemistry , Gelatin/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Surgical Wound/drug therapy , Wound Healing/drug effects , Animals , Bandages , Biomimetic Materials/pharmacology , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Chemokine CCL2/antagonists & inhibitors , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Extracellular Matrix/chemistry , Gelatin/pharmacology , Gene Expression , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Male , Methacrylates/chemistry , Mice , Mice, Inbred ICR , NIH 3T3 Cells , Rats , Rats, Sprague-Dawley , Skin/drug effects , Skin/injuries , Skin/metabolism , Streptozocin , Surgical Wound/metabolism , Surgical Wound/pathology , Wound Healing/physiology
17.
Macromol Biosci ; 17(7)2017 07.
Article in English | MEDLINE | ID: mdl-28346751

ABSTRACT

d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N3 /TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids. Also, the presence of free d-fructose competitively inhibits the internalization of PPF MM in MCF-7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF-7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5-mediated cell specific delivery in cancer therapy.


Subject(s)
Breast Neoplasms , Drug Carriers , Fructose , Glucose Transporter Type 5/metabolism , Micelles , Neoplasm Proteins/metabolism , Polyesters , Polyethylene Glycols , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Fructose/chemistry , Fructose/pharmacokinetics , Fructose/pharmacology , Humans , MCF-7 Cells , Mice , Mice, Nude , Polyesters/chemistry , Polyesters/pharmacokinetics , Polyesters/pharmacology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/pharmacology , Xenograft Model Antitumor Assays
18.
Sci Total Environ ; 468-469: 578-83, 2014 Jan 15.
Article in English | MEDLINE | ID: mdl-24056448

ABSTRACT

Penguins play important roles in the biogeochemical cycle between Antarctic Ocean and land ecosystems. The roles of emperor penguin Aptenodytes forsteri, however, are usually ignored because emperor penguin breeds in fast sea ice. In this study, we collected two sediment profiles (EPI and PI) from the N island near a large emperor penguin colony at Amanda Bay, East Antarctic and performed stable isotope and element analyses. The organic C/N ratios and carbon and nitrogen isotopes suggested an autochthonous source of organic materials for the sediments of EPI (C/N = 10.21 ± 0.28, n = 17; δ(13)C = -13.48 ± 0.50‰, δ(15)N = 8.35 ± 0.55‰, n = 4) and an allochthonous source of marine-derived organic materials for the sediments of PI (C/N = 6.15 ± 0.08, δ(13)C = -26.85 ± 0.11‰, δ(15)N = 21.21 ± 2.02‰, n = 20). The concentrations of total phosphorus (TP), selenium (Se), mercury (Hg) and zinc (Zn) in PI sediments were much higher than those in EPI, the concentration of copper (Cu) in PI was a little lower, and the concentration of element lead (Pb) showed no difference. As measured by the geoaccumulation indexes, Zn, TP, Hg and Se were from moderately to very strongly enriched in PI, relative to local mother rock, due to the guano input from juvenile emperor penguins. Because of its high trophic level and transfer efficiency, emperor penguin can transport a large amount of nutrients and contaminants from ocean to land even with a relatively small population, and its roles in the biogeochemical cycle between ocean and terrestrial environment should not be ignored.


Subject(s)
Environmental Pollutants/metabolism , Feces/chemistry , Geologic Sediments/chemistry , Spheniscidae/metabolism , Animals , Antarctic Regions , Carbon Isotopes/metabolism , Geography , Islands , Mercury/analysis , Nitrogen Isotopes/metabolism , Oceans and Seas , Phosphorus/analysis , Selenium/analysis , Species Specificity , Statistics, Nonparametric , Zinc/analysis
19.
Ying Yong Sheng Tai Xue Bao ; 19(7): 1597-603, 2008 Jul.
Article in Chinese | MEDLINE | ID: mdl-18839925

ABSTRACT

A field survey was conducted on the species composition, community type, distribution pattern, and biomass of aquatic vegetations in the Baiyangdian Lake of Hebei Province. A total of 39 species were observed, including 16 emergent species, 14 submerged species, 6 floating-leaved species, and 3 floating species, belonging to 21 families and 32 genera. Compared with those about 15 years ago, 9 species were disappeared, community types were decreased from 16 to 13, and some predominant communities with large distribution area, such as Hydrilla verticillata and Najas major, were not found in the present survey. Meanwhile, the distribution pattern of aquatic vegetations was greatly changed. The biomass of aquatic vegetations decreased dramatically, compared to the survey in 1980. Human cultivation, random discharge of pollutants, and tremendous change of water level could be the main reasons for the degradation of aquatic vegetations and the great change of their distribution pattern in the Lake.


Subject(s)
Biodiversity , Biomass , Fresh Water/analysis , Plant Development , Alismatales/growth & development , China , Environmental Monitoring , Geography , Hydrocharitaceae/growth & development , Plants/classification
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