Zeolitic imidazolate framework-8: a versatile nanoplatform for tissue regeneration.

Extensive research on zeolitic imidazolate framework (ZIF-8) and its derivatives has highlighted their unique properties in nanomedicine. ZIF-8 exhibits advantages such as pH-responsive dissolution, easy surface functionalization, and efficient drug loading, making it an ideal nanosystem for intelligent drug delivery and phototherapy. These characteristics have sparked significant interest in its potential applications in tissue regeneration, particularly in bone, skin, and nerve regeneration. This review provides a comprehensive assessment of ZIF-8's feasibility in tissue engineering, encompassing material synthesis, performance testing, and the development of multifunctional nanosystems. Furthermore, the latest advancements in the field, as well as potential limitations and future prospects, are discussed. Overall, this review emphasizes the latest developments in ZIF-8 in tissue engineering and highlights the potential of its multifunctional nanoplatforms for effective complex tissue repair.

A Photochemically Active Cu2O Nanoparticle Endows Scaffolds with Good Antibacterial Performance by Efficiently Generating Reactive Oxygen Species.

Cuprous oxide (Cu2O) has great potential in photodynamic therapy for implant-associated infections due to its good biocompatibility and photoelectric properties. Nevertheless, the rapid recombination of electrons and holes weakens its photodynamic antibacterial effect. In this work, a new nanosystem (Cu2O@rGO) with excellent photodynamic performance was designed via the in situ growth of Cu2O on reduced graphene oxide (rGO). Specifically, rGO with lower Fermi levels served as an electron trap to capture photoexcited electrons from Cu2O, thereby promoting electron-hole separation. More importantly, the surface of rGO could quickly transfer electrons from Cu2O owing to its excellent conductivity, thus efficiently suppressing the recombination of electron-hole pairs. Subsequently, the Cu2O@rGO nanoparticle was introduced into poly-L-lactic acid (PLLA) powder to prepare PLLA/Cu2O@rGO porous scaffolds through selective laser sintering. Photochemical analysis showed that the photocurrent of Cu2O@rGO increased by about two times after the incorporation of GO nanosheets, thus enhancing the efficiency of photogenerated charge carriers and promoting electron-hole separation. Moreover, the ROS production of the PLLA/Cu2O@rGO scaffold was significantly increased by about two times as compared with that of the PLLA/Cu2O scaffold. The antibacterial results showed that PLLA/Cu2O@rGO possessed antibacterial rates of 83.7% and 81.3% against Escherichia coli and Staphylococcus aureus, respectively. In summary, this work provides an effective strategy for combating implant-related infections.

Zeolitic Imidazolate Frameworks Serve as an Interface Layer for Designing Bifunctional Bone Scaffolds with Antibacterial and Osteogenic Performance.

The integration of hydroxyapatite (HA) with broad-spectrum bactericidal nano-silver within biopolymer-based bone scaffolds not only promotes new bone growth, but also effectively prevents bacterial infections. However, there are problems such as a poor interface compatibility and easy agglomeration. In this project, zeolitic imidazolate frameworks (ZIF-8) were grown in situ on nano-HA to construct a core-shell structure, and silver was loaded into the ZIF-8 shell through ion exchange. Finally, the core-shell structure (HA@Ag) was composited with polylactic acid (PLLA) to prepare bone scaffolds. In this case, the metal zinc ions of ZIF-8 could form ionic bonds with the phosphate groups of HA by replacing calcium ions, and the imidazole ligands of ZIF-8 could form hydrogen bonds with the carboxyl groups of the PLLA, thus enhancing the interface compatibility between the biopolymers and ceramics. Additionally, the frame structure of MOFs enabled controlling the release of silver ions to achieve a long-term antibacterial performance. The test results showed that the HA@Ag nanoparticles endowed the scaffold with good antibacterial and osteogenic activity. Significantly, the HA@Ag naoaprticle exhibited a good interfacial compatibility with the PLLA matrix and could be relatively evenly dispersed within the matrix. Moreover, the HA@ZIF-8 also effectively enhanced the mechanical strength and degradation rate of the PLLA scaffold.

Hyaluronic acid encapsulated silver metal organic framework for the construction of a slow-controlled bifunctional nanostructure: Antibacterial and anti-inflammatory in intrauterine adhesion repair.

Intrauterine adhesion (IUA) is a common gynecological disease caused by endometrial injury, which might result in abnormal menstruation, miscarriage, and even fetal deaths. Nevertheless, existing treatment strategies such as intrauterine device and uterine cavity balloons only provide a physical barrier, and not circumvent inflammation of endometrial microenvironment and retrograde infection. In this study, a slow-controlled bifunctional nanostructure was developed via encapsulating hyaluronic acid (HA) on surface of silver-metal organic framework (Ag-MOF), and then loaded in poly lactic-co-glycolic acid scaffold to prevent IUA. In therapy, macro-molecule of HA provided anti-inflammatory function by the adjustment of signal transduction pathways of macrophage surface receptors, whereas Ag-MOF inactivated bacteria by destroying bacterial membrane and producing reactive oxygen. Significantly, the coated HA effectively avoided burst release of Ag+, thus achieving long-term antibacterial property and good biocompatibility. Antibacterial results showed antibacterial rate of the scaffold reached 87.8 % against staphylococcus aureus. Anti-inflammatory assays showed that the scaffold inhibited the release of inflammatory cytokines and promoted the release of anti-inflammatory cytokines. Moreover, in vitro cell tests revealed that the scaffold effectively inhibited fibroblast growth, indicating its good ability to prevent IUA. Taken together, the scaffold may be a promising candidate for IUA treatment.

Screening and identification of tyrosinase inhibitors in edible plant materials by on-line UPLC-enzyme reactor coupled with UHPLC-FTMS.

Tyrosinase plays a primary role in melanin biosynthesis and enzymatic browning of freshly cut fruits and vegetables. Herein, an on-line ultraperformance liquid chromatography diode array detector biochemical detection (UPLC-DAD-BCD) method was established to identify trace amount potent tyrosinase inhibitors and antibrowning agents in complex mixtures. The tyrosinase inhibition activities of some representative compounds were evaluated by using the established method and their chromatography-activity relationships were obtained. Then the proposed UPLC-DAD-BCD method was applied to screen tyrosinase inhibitors in edible herbal extracts and identified two tyrosinase inhibitors in green tea and three in cinnamon. The above active ingredients were determined by ultra-high-performance liquid chromatography linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-FTMS). The on-line UPLC-DAD-BCD in combination with UHPLC-FTMS was confirmed to be a powerful technique to screen and elucidate the active ingredients in complex matrixes and could be applied to evaluate the integrated effects of multiple ingredients against corresponding targets.

In Situ Growth of a Metal-Organic Framework on Graphene Oxide for the Chemo-Photothermal Therapy of Bacterial Infection in Bone Repair.

Bacterial infection with high morbidity (>30%) seriously affects the defect's healing after bone transplantation. To this end, chemotherapy and photothermal therapy have been utilized for antibacterial treatment owing to their high selectivity and minimal toxicity. However, they also face several dilemmas. For example, bacterial biofilms prevented the penetration of antibacterial agents and local temperatures (over 70 °C) caused by the photothermal therapy damaged normal tissue. Herein, a co-dispersion nanosystem with chemo-photothermal function was constructed via the in situ growth of zeolitic imidazolate framework-8 (ZIF-8) on graphene oxide (GO) nanosheets. In this nanosystem, GO generates a local temperature (∼50 °C) to increase the permeability of a bacterial biofilm under near-infrared laser irradiation. Then, Zn ions released by ZIF-8 seized this chance to react with the bacterial membrane and inactivate it, thus realizing efficient sterilization in a low-temperature environment. This antibacterial system was incorporated into a poly-l-lactic acid scaffold for bone repair. Results showed that the scaffold showed a high antibacterial rate of 85% against both Escherichia coli and Staphylococcus aureus. In vitro cell tests showed that the scaffold promoted cell proliferation.

Generating Pure Spin Current in Heterojunction Organic Solar Cells.

We propose a mechanism for generating pure spin current in heterojunction organic solar cells, with the donor and acceptor both being degenerate ground-state polymers; thus, solitons can be formed. This mechanism contains the following steps: (i) the donor is photoexcited to create the electron-hole (e-h) pairs; (ii) the excited electrons are transferred to the acceptor; (iii) the net charges in the donor and acceptor are evolved into the localized charged solitons; (iv) the intermolecule bias is applied to drive the transferred electrons back to donor, and concomitantly, charged solitons are converted to neutral solitons. Here, the on-site Coulomb interaction plays an important role in ensuring the neutral solitons' spins in the donor and acceptor are oppositely polarized. Because spins are separated between the donor and acceptor without any charge separations, pure spin current can be formed. Our mechanism opens a new avenue for exploring potential organic spintronic devices.

Pharmacokinetic and tissue distribution study of eight volatile constituents in rats orally administrated with the essential oil of Artemisiae argyi Folium by GC-MS/MS.

Artemisia argyi is commonly used as a remedy for gynecological and respiratory disease in traditional Chinese medicine. The essential oil is considered as the major active ingredients of A. argyi, mainly composed of eucalyptol, α-thujone, camphor, borneol, bornyl acetate, eugenol, ß-caryophyllene, and caryophyllene oxide, while limited study addresses the in vivo disposition of these volatile ingredients. In present study, a rapid, sensitive and selective GC-MS/MS method has been developed and validated for the quantification of the eight volatile constituents in rat plasma and tissues after orally dosing with the essential oil of Artemisiae Argyi Folium (AAEO) using naphthalene as an internal standard (IS). The analytes were extracted from biosamples by liquid-liquid extraction with hexane/ethyl acetate. The GC separation was achieved on a TG-5SILMS column (30 m × 0.25 mm, 0.25 µm film thickness) and MS detection was performed on selective reaction monitoring (SRM) mode. The assay had a lower limit of quantification (LLOQ) less than 2 ng/ml for the analytes with good linearity (r ≥ 0.9907). Their disposition profile in rat plasma and tissues was characterized after orally giving AAEO, and the data revealed the analytes underwent rapid absorption from GI tract and were mainly transferred to the liver, heart, kidney, lung, and spleen with prompt elimination. The results provided a meaningful basis for guiding the pharmacodynamic study and clinical applications of this herbal medicine.

Graphene-assisted barium titanate improves piezoelectric performance of biopolymer scaffold.

Biopolymer scaffold is expected to generate electrical stimulation, aiming to mimic an electrical microenvironment to promote cell growth. In this work, graphene and barium titanate (BT) was introduced into selective laser sintered poly-l-lactic acid (PLLA) scaffold. BT as one piezoelectric ceramic was used as the piezoelectric source, whereas graphene served as superior conductive filler. Significantly, the incorporated graphene enhanced the electrical conductivity and thereby increased the electric field strength applied on BT nanoparticles during poling. In this case, more electric domain within BT rearranged along the poling field direction, thus promoting the piezoelectric response of the composites. Results showed that the PLLA/BT/graphene scaffold exhibited relatively high output voltage of 1.4 V and current of 10 nA. Cells tests proved that these electrical signals considerably promoted cell proliferation and differentiation. Moreover, the scaffold exhibited improved mechanical properties due to the rigid particle enhancement effect and increased crystallinity.

Surface modification enhances interfacial bonding in PLLA/MgO bone scaffold.

The poor interfacial bonding and resultant agglomeration of nanoparticles in polymer-based composite severely deteriorated their reinforcement effect. In this work, MgO nanoparticles (MgO-NPs) were surface modified with Poly (L-lactic acid-co-malic acid) (PLMA) to improve the interfacial compatibility in Poly-l-lactic acid (PLLA) scaffold manufactured by selective laser sintering. PLMA possess a hydrophilic end with carboxyl group (comes from the malic acid) and an l-lactic acid chain. On one hand, the carboxyl group was able to form hydrogen bonding with the hydroxyl groups of MgO-NPs. On the other hand, the l-lactic acid chain containing the hydroxyl groups could react with the carboxyl group of PLLA. Results revealed that the scaffold exhibited significantly enhanced compressive strength and modulus by 47.1% and 237.7%, respectively, which could be ascribed to the enhanced interfacial bonding between PLLA and MgO-NPs, as well as the rigid particle reinforcement. In addition, the scaffold was favorable for cell adhesion, proliferation and differentiation, owing to the improved hydrophilic and suitable pH environment. It was suggested the scaffold was a promising material for bone repair application.

Simultaneous determination of phenolic acids and flavonoids in Artemisiae Argyi Folium by HPLC-MS/MS and discovery of antioxidant ingredients based on relevance analysis.

A rapid and reliable LC-MS/MS method was developed for the quantitation of major components in Folium Artemisiae Argyi (mugwort), a widely used traditional Chinese herbal medicine. A total of 5 phenolic acids and 17 flavonoids were separated and simultaneously determined by using a Shiseido C18 column (150 × 3.0 mm, 3 µm) and gradient elution of acetonitrile-aqueous formic acid (100:0.1, v/v) at a 0.5 mL min-1 flow rate, via multiple reaction monitor (MRM) in polarity switching mode. The quantitative method was validated in terms of sensitivity, linearity, precision, accuracy and stability, which proved to be sensitive, accurate and reproducible. Then 65 samples collected from different areas were selected for component analysis by LC-MS/MS and assessment of antioxidant activity using DPPH, ABTS, FRAP, O2- and OH scavenging assays. Grey relational analysis and partial least square regression were used to evaluate the relevance between chemicals and bioactivities, and the results indicated chlorogenic acid, isochlorogenic acid B, A, C, eriodictyol, jaceosidin and eupatilin made the key contribution to antioxidant activity. The present study combines chemical analysis and bioassay to identify bioactive markers, which possesses potential value for the activity-oriented quality control of mugwort.

Network Pharmacology Deciphering Mechanisms of Volatiles of Wendan Granule for the Treatment of Alzheimer's Disease.

OBJECTIVE: To explore the mechanisms of the volatiles of Wendan granule (WDG) for the treatment of Alzheimer's disease, network pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, target fishing, network constructing, pathway analysing, and correlated diseases prediction was applied. METHODS: Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2 %, and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and the corresponding targets, genes, pathways, and diseases were predicted according to the data provided by TCMSP, DrugBank, Uniport, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the related pathways and correlation analysis were explored by the Kyoto Encyclopedia and Genomes (KEGG) database. Finally, the networks of compound target, target pathway, and pathway disease of WDG were constructed by Cytoscape software. RESULTS: Twelve compounds interacted with 49 targets, of which top three targets were gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), prostaglandin G/H synthase 2 (PGHS-2), and sodium-dependent noradrenaline transporter. Interestingly, these targets were highly associated with depression, insomnia, and Alzheimer's disease that mainly corresponded to mental and emotional illnesses. CONCLUSION: The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of the main volatiles of WDG for relieving senile dementia related syndromes, which will also facilitate the application of traditional Chinese medicine as an alternative or supplementary to conventional treatments of AD, as well as follow-up studies such as upgrading the quality standard of clinically applied herbal medicine and novel drug development.

Effect of Poria cocos hydroethanolic extract on treating adriamycin-induced rat model of nephrotic syndrome.

OBJECTIVE: To evaluate the effect of Poria cocos (Schw.) Wolf hydroethanolic extract (PHE) against nephrotic syndrome (NS) in rats and to identify the potential active components from PHE. METHODS: The high content compounds were isolated and purified by using column chromatography followed by preparative highperformance liquid chromatography (p-HPLC). Forty male Wistar rats with adriamycin (ADR)-induced NS were randomly divided into 5 groups, 8 in each group: model control group, positive control group (with prednisone treatment), PHE low-dose group, PHE middle-dose group and PHE high-dose group. Another 8 rats were recruited as vehicle control group. All rats received the intragastric administration of corresponding drugs or saline for 30 days. During the experimental period, rats' behavior and appearance were observed and recorded daily, and their body weights were recorded weekly. After treatment, 24-h urine samples were collected to evaluate the urine protein and urine creatinine (Ucr); then the rats were sacrificed to collect carotid blood and to determine the levels of serum total protein (TP), albumin (Alb), globulin (Glo), total cholesterol (TC) and cytokine interlukin-4 (IL-4). RESULTS: Six acidic components were isolated and identified from the PHE section: pachymic acid, 15α-hydroxydehydrotumulosic acid, trametenolic acid, dehydropachymic acid, 3ß-hydroxy-lanosta-7,9(11), 24-trien-21-oic-acid and dehydroeburicoic acid. Compared with the model control group, the urine protein content were significantly decreased in the PHE treatment groups and positive control group (P<0.05), especially PHE middle-dose group (P<0.01). The Ucr values and serum levels of TP, Glo, TC and IL-4 in PHE low- and middle-dose groups were also presented obvious recover tendency as compared with the model control group (P<0.05 or P<0.01). However, positive control group and all PHE groups indicated no significant therapeutic effect on raising Alb value, although PHE low- and middle-dose treatment groups showed better outcomes than positive control group (P>0.05). CONCLUSIONS: PHE showed an encouraging therapeutic effect against ADR-induced NS in a rat model. PHE might be a group of effective substances for the treatment of NS.

Headspace, solid-phase micro-extraction, gas chromatographic-mass spectrometric analysis of terpenoids in the latex of Euphorbia species.

The volatile and semi-volatile terpenoids in the latex of Euphorbia amygdaloides, E. exigua, E. helioscopia, and E. peplus were analyzed by headspace, solid-phase micro-extraction (HS-SPME), coupled with gas chromatography-mass spectrometry. The volatiles were extracted using a 100 microm polydimethylsiloxane SPME fiber under optimized extraction conditions. The compounds detected encompassed a range of chemical classes, but only terpenoids were evaluated. Only sesquiterpene hydrocarbons were detected in the tested samples of E. exigua, E. helioscopia, and E. peplus, with beta-caryophyllene being the major one, but were never recorded in latex samples of E. amygdaloides, in which only the diterpene hydrocarbon kaur-16-ene was detected. Alpha-Humulene was consistently found in samples of E. helioscopia, and E. peplus, but never in those of the other two species. These preliminary results show that the developed procedure is suitable for the analysis of small samples of Euphorbia latex and that, for each individual species, there is very little qualitative difference between samples, regardless of either place or date of collection.

[Study of hypoxia-induced immune injury and its intervention measure].

OBJECTIVE: To explore the characteristic of hypoxia-induced immune injury, its mechanisms and the intervention measure. METHODS: The change of immune organ index, T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ, pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice. RESULTS: (1) Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4+ CD8+ thymocytes and marked increase in CD4+ CD8-, CD4- CD8+ thymocytes (P < 0.01). After 3 days of hypoxia, the mice had a much lower percentage of CD4+ T-cell (P < 0.05). The ratio of CD4+/CD8+ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte (P < 0.05). After 6 days of hypoxia, index of spleen was significantly increased (P < 0.05), index of thymus was significantly decreased (P < 0.05) and CD3+, CD4+, CD8+ lymphocyte percentage of spleen were significantly decreased (P < 0.01). Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased (P < 0.01), viable cell rates of spleen lymphocyte and thymocytes were markedly decreased (P < 0.01), early apoptosis rates of spleen lymphocyte were markedly increased (P < 0.01). There was no significant change in the percentage of CD8+ lymphocyte in peripheral blood during the whole hypoxia period. (2) New Compound Codonopsis Pilosula (NCCP), Xiang Qi Polysaccharide (XQP) and NCCP + XQP could significantly increase the number of peripheral blood CD3+, CD4+ and spleen CD4+, but had no significant influence on the number of spleen CD8+. XQP and XQP+ NCCP could significantly decrease the number of CD4+ CD8+ (P < 0.01), increase that of CD4+ CD8- (P < 0.01), and had no significant influence on CD4- CD8+ in thymus. However, NCCP didn't influence the component of thymocytes. CONCLUSION: After hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte, and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.