Preparation of gastrodin modified P(VDF-TrFE)-Eudragit L100-AuNPs nanofiber membranes with piezoelectric property.

In recent years, electroactive nerve conduits made from a blend of P(VDF-TrFE) (poly (vinylidene fluoride-trifluoroethylene)) with other materials have shown significant progress. However, research combining P(VDF-TrFE) conduits with drug delivery systems remains sparse. In this study, we developed a novel gastrodin-loaded P(VDF-TrFE)-Eudragit L100-gold nanoparticles (Gas@PT-EL100-AuNPs) nanofiber membrane. Fabricated through electrospinning technique, this composite membrane aimed to investigate the impacts of gastrodin and AuNPs on its properties. Experimental results indicated that the incorporation of gold nanoparticles significantly reduced the fiber diameter of the membrane and enhanced the overall performance by improving hydrophilicity and piezoelectric properties. Specifically, the addition of AuNPs substantially enhanced the piezoelectric performance of the nanofiber membrane. Furthermore, the inclusion of gastrodin not only improved the membrane's hydrophilicity but also enabled effective release of the neuroprotective drug. These findings suggest that the Gas@PT-EL100-AuNPs nanofiber membrane is a novel biomaterial with potential applications in the repair and treatment of nerve injuries.

Human cytomegalovirus in cancer: the mechanism of HCMV-induced carcinogenesis and its therapeutic potential.

Cancer is one of the leading causes of death worldwide. Human cytomegalovirus (HCMV), a well-studied herpesvirus, has been implicated in malignancies derived from breast, colorectal muscle, brain, and other cancers. Intricate host-virus interactions are responsible for the cascade of events that have the potential to result in the transformed phenotype of normal cells. The HCMV genome contains oncogenes that may initiate these types of cancers, and although the primary HCMV infection is usually asymptomatic, the virus remains in the body in a latent or persistent form. Viral reactivation causes severe health issues in immune-compromised individuals, including cancer patients, organ transplants, and AIDS patients. This review focuses on the immunologic mechanisms and molecular mechanisms of HCMV-induced carcinogenesis, methods of HCMV treatment, and other studies. Studies show that HCMV DNA and virus-specific antibodies are present in many types of cancers, implicating HCMV as an important player in cancer progression. Importantly, many clinical trials have been initiated to exploit HCMV as a therapeutic target for the treatment of cancer, particularly in immunotherapy strategies in the treatment of breast cancer and glioblastoma patients. Taken together, these findings support a link between HCMV infections and cellular growth that develops into cancer. More importantly, HCMV is the leading cause of birth defects in newborns, and infection with HCMV is responsible for abortions in pregnant women.

Advances in Large Gap Peripheral Nerve Injury Repair and Regeneration with Bridging Nerve Guidance Conduits.

Peripheral nerve injury is a common complication of accidents and diseases. The traditional autologous nerve graft approach remains the gold standard for the treatment of nerve injuries. While sources of autologous nerve grafts are very limited and difficult to obtain. Nerve guidance conduits are widely used in the treatment of peripheral nerve injuries as an alternative to nerve autografts and allografts. However, the development of nerve conduits does not meet the needs of large gap peripheral nerve injury. Functional nerve conduits can provide a good microenvironment for axon elongation and myelin regeneration. Herein, the manufacturing methods and different design types of functional bridging nerve conduits for nerve conduits combined with electrical or magnetic stimulation and loaded with Schwann cells, etc., are summarized. It summarizes the literature and finds that the technical solutions of functional nerve conduits with electrical stimulation, magnetic stimulation and nerve conduits combined with Schwann cells can be used as effective strategies for bridging large gap nerve injury and provide an effective way for the study of large gap nerve injury repair. In addition, functional nerve conduits provide a new way to construct delivery systems for drugs and growth factors in vivo.

Multifunctional electrospun membranes with hydrophilic and hydrophobic gradients property for wound dressing.

Achieving sustained and stable release of macromolecular antibacterial agents and unidirectional transport of liquids in targeted environment is still a challenge to be addressed in the management of wounds with large amounts of tissue exudates. In this work, a multilayer electrospun membrane (ethylcellulose-ethylcellulose/gelatin-quercetin/Eudragit L-100/polyethylene glycol, EC-EC/Gel-Q/EL/PEG) was designed with hydrophobic-hydrophilic gradients and drug sustained-release properties controlled by self-pumping effect and prepared using sequential electrospinning technology. The capillary force of different layers in the multilayer membrane could be controlled by precisely tuning the polymer concentrations of the inner and middle layers to extract water directly from hydrophobic inner ethylcellulose (EC) layer to hydrophilic middle ethylcellulose/gelatin (EC/Gel) layer. The droplets could not penetrate the hydrophobic side, but the drug molecules in the outer layer quercetin-loaded Eudragit L-100 (Q/EL/PEG) membrane moved after absorbing a large amount of water. The drug release behavior of multilayer wound dressing mainly followed the Korsmeyer-Peppas model. This multifunctional electrospun membrane could rapidly drive the biofluid outflow, effectively block the invasion of external contaminants and continuously release anti-inflammatory drugs, without any obvious cytotoxicity to mouse fibroblast cells. Hence, the above results indicate the excellent therapeutic potential of the proposed biomaterial as a wound dressing for diabetic patients.

Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection.

RNA therapy represents a great way to precisely regulate cellular processes by modulating the gene expression. Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self-regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed. To demonstrate the efficacy of this delivery system, we used it to treat human cytomegalovirus (HCMV) infection in a humanized mouse model. In this study, we use small interfering RNA (siRNA) and small complementary RNA (scRNA) to inhibit the expressions of two HCMV genes, IE1 and IE2. The auto-regulated nanocarrier polywraplex with core-shell structure was designed to condense and package these RNAs for delivering. To allow these particles recognize the HCMV-infected cells, a ligand was coupled on the surface of nanoparticle, which would specifically target the HCMV-encoded CX3 CL1 chemokine receptor presented in the HCMV-infected cells. The results demonstrated that the polywraplex conjugated with the target molecule CX3 CL1 effectively and specifically delivered the siRNA/scRNA to HCMV infected cells and inhibited virus growth in vitro and in vivo.

Effects of Various Marine Toxins on the Mouse Intestine Organoid Model.

Because of their trace existence, exquisite structure and unique role, highly toxic marine biotoxins have always led to the development of natural product identification, structure and function research, chemistry and biosynthesis, and there are still many deficiencies in the injury and protection of highly toxic organisms, toxin biosynthesis, rapid detection, poisoning and diagnosis and treatment. In this study, a mouse intestine organoid (MIO) model was constructed to explore the effects of the marine toxins okadaic acid (OA) and conotoxin (CgTx) on MIO. The results showed that the cell mortality caused by the two toxins at middle and high concentrations was significantly higher than the cell mortality of the control group, the ATPase activity in each group exposed to OA was significantly lower than the ATPase activity of the control group, all the CgTx groups were significantly higher than that of the control group, and the number of apoptotic cells was not significantly higher than the number of apoptotic cells of the control group. Through RNA-Seq differential genes, Gene Ontology (GO) and pathway analysis, and Gene Set Enrichment Analysis (GSEA) experimental results, it was demonstrated that OA reduced cell metabolism and energy production by affecting cell transcription in MIO. Ultimately, cell death resulted. In contrast, CgTx upregulated the intracellular hormone metabolism pathway by affecting the nuclear receptor pathway of MIO, which resulted in cell death and the generation of energy in large amounts.

The role of essential oils in maintaining the postharvest quality and preservation of peach and other fruits.

Fruits are highly susceptible to postharvest losses induced majorly by postharvest diseases. Peach are favored by consumers because of their high nutritional value and delicious taste. However, it was easy to be affected by fungal infection. The current effective method to control postharvest diseases of fruits is to use chemical fungicides, but these chemicals may cause adverse effects on human health and the residual was potentially harmful to nature and the environment. So, it is especially important to develop safe, non-toxic, and highly effective strategies for the preservation of the fruits. Essential oil, as a class of the natural bacterial inhibitor, has been proven to exhibit strong antibacterial activity, low toxicity, environmental friendliness, and induce fruit resistance to microorganism, which could be recognized as one of the alternatives to chemical fungicides. This paper reviews the research progress of essential oils (Eos) in the storage and preservation of fruits, especially the application in peach, as well as the application in active packaging such as edible coatings, microcapsules, and electrospinning loading. Electrospinning can prepare a variety of nanofibers from different viscoelastic polymer solutions, and has broad application prospects. The paper especially summarizes the application of the new Eos technology on peach. The essential oil with thymol, eugenol, and carvacrol as the main components has a better inhibitory effect on the postharvest disease of peaches, and can be further applied. PRACTICAL APPLICATIONS: As an environmentally friendly natural antibacterial agent, essential oil can be used as a substitute for chemical preservatives to keep fruits fresh. This paper summarizes the different preservation methods of essential oils for fruits, and especially summarizes the different preservation methods of essential oils for peaches after harvesting, as well as their inhibitory effects on pathogenic fungi. It could provide ideas for preservation of fruits and vegetables by essential oils.

Preparation of curcumin-loaded cochleates: characterisation, stability and antioxidant properties.

Curcumin (CUR) has a wide range of applications in functional foods. However, it has some disadvantages such as poor water solubility and stability. To solve these problems, CUR was encapsulated into cochleates with an encapsulation efficiency of 83.66% and a diameter of about 403.9 nm. The study found that the stability of CUR-loaded cochleates (CUR-Cochs) was improved when compared with that of the curcumin-loaded liposomes (CUR-Lipos). Additionally, it showed that the DPPH scavenging ability of CUR-Cochs was equivalent to free CUR. In addition, 3 µM CUR-Cochs could significantly reduce the MDA content and the LDH release, and increased SOD activity in the H2O2 induced NIH3T3 cell oxidative damage model. The expression of Nrf2 and NQO1 proteins were obviously increased in the CUR-Cochs group, indicating that CUR-Cochs could effectively reduce NIH3T3 cell damage caused by H2O2. The CUR-Cochs could improve the stability of CUR with a desired anti-oxidation ability, which may mean that it is feasible for it to be applied further in functional foods.

Preparation of Polyvinylidene Fluoride-Gold Nanoparticles Electrospinning Nanofiber Membranes.

In this work, gold nanoparticles (AuNPs) and curcumin drug were incorporated in polyvinylidene fluoride (PVDF) nanofibers by electrospinning as a novel tissue engineering scaffold in nerve regeneration. The influence of AuNPs on the morphology, crystallinity, and drug release behavior of nanofiber membranes was characterized. A successful composite nanofiber membrane sample was observed by scanning electron microscopy (SEM). The addition of AuNPs showed the improved as well as prolonged cumulative release of the drug. The results indicated that PVDF-AuNPs nanofiber membrane could potentially be applied for nerve regeneration.

The Antioxidant Effect of the Metal and Metal-Oxide Nanoparticles.

Inorganic nanoparticles, such as CeO3, TiO2 and Fe3O4 could be served as a platform for their excellent performance in antioxidant effect. They may offer the feasibility to be further developed for their smaller and controllable sizes, flexibility to be modified, relative low toxicity as well as ease of preparation. In this work, the recent progress of these nanoparticles were illustrated, and the antioxidant mechanism of the inorganic nanoparticles were introduced, which mainly included antioxidant enzyme-mimetic activity and antioxidant ROS/RNS scavenging activity. The antioxidant effects and the applications of several nanoparticles, such as CeO3, Fe3O4, TiO2 and Se, are summarized in this paper. The potential toxicity of these nanoparticles both in vitro and in vivo was well studied for the further applications. Future directions of how to utilize these inorganic nanoparticles to be further applied in some fields, such as medicine, cosmetic and functional food additives were also investigated in this paper.

Study on the Preparation, Characterization, and Stability of Freeze-Dried Curcumin-Loaded Cochleates.

Curcumin (CUR), a polyphenolic substance extracted from plants, has extensive pharmacological activities. However, CUR is difficult to be absorbed in the body due to its poor stability and low solubility. Studies have found that cochleates can be used as a new delivery system to encapsulate bioactive agents for the purpose of improving its stability and bioavailability. In this study, thin-film dispersion and trapping methods were used to prepare curcumin-loaded cochleates (CUR-Cochs). Then CUR-Cochs were characterized and the encapsulation efficiency was determined by HPLC. In addition, the freeze-drying process of CUR-Cochs was studied and related characterization was performed. CCK-8 assay was used to detect the cytotoxicity of cochleates carrier. Additionally, H2O2-induced cellular oxidative damage model were used to evaluate its antioxidant capacity. The results showed that the structure of CUR-Cochs was a spiral cylinder with an average particle size of 463.8 nm and zeta potential of -15.47 mV. The encapsulation efficiency was the highest (83.66 ± 0.8)% with 1:50 CUR-to-lipid mass ratio. In vitro results showed that cochleates had negligible cytotoxicity and owned antioxidant capacity, which provided the possibility for their applications in food and medicine. In general, the method herein might be a promising method to encapsulate CUR for further use as a bioactive agent in functional foods.

Chitosan nanoparticles embedded with curcumin and its application in pork antioxidant edible coating.

Curcumin (Cur) exhibits low water solubility and insufficient dispersibility in food systems, and cannot exert its excellent antioxidant properties. In this work, Chitosan (CS) nanoparticles were prepared by ionic crosslinking method using chitosan as carrier and sodium tripolyphosphate (TPP) as crosslinking agent, then Cur was loaded to obtain curcumin nanoparticles (CNPs). CNPs presented a spherical morphology with average size of 278.9 nm. Compared with the solubility of native Cur (0.017 µg/mL) at 25 °C, the water solubility of CNPs increased to 35.92 µg/mL of more than 2100 times. In addition, the antioxidant capacity of Cur was also studied based on DPPH free radical scavenging, the results showed that with the increase of the concentration, the antioxidant capacity of CNPs was significantly increased (p < 0.05), which was higher than that of Cur at the same concentration. The edible coating was prepared by adding CNPs into sodium carboxymethyl cellulose (CMC) to study the effects of CMC-CNPs coatings in improving the quality and shelf life of fresh pork stored at 4 ± 1 °C for 15 days. The results showed that CMC-CNPs edible coating could significantly inhibit lipid oxidation of fresh pork (p < 0.05) and could be further applied in lipid rich food packaging.

1,2,4-Triazole hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has developed numerous mechanisms of virulence and strategies to evade the human immune system, and it can be transmitted between humans, animals, and the environment. Thus, MRSA is an important cause of morbidity and mortality in both hospitals and in the community, creating an urgent demand for the development of novel anti-MRSA candidates. The 1,2,4-triazole nucleus is a bioisostere of amide, ester, and carboxylic acid, and the 1,2,4-triazole ring is found in many compounds with diverse biological effects. 1,2,4-Triazole derivatives could exert their antibacterial activity through inhibition of efflux pumps, filamentous temperature-sensitive protein Z, penicillin-binding protein, DNA gyrase, and topoisomerase IV, and they play an important role in the discovery of novel antibacterial agents. Among them, 1,2,4-triazole hybrids, which have the potential to exert dual/multiple mechanisms of action, possess a promising broad-spectrum antibacterial activity against a panel of clinically important drug-resistant pathogens including MRSA. This review outlines the recent developments of 1,2,4-triazole hybrids with a potential anti-MRSA activity, covering articles published between 2010 and 2020. The mechanisms of action, critical aspects of their design, and structure-activity relationships are also discussed.

Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors.

Over the years, the manipulation and clinical application of drug-delivery nanosystems for cancer diseases have attracted a rapid growth of academic research interests, and some nanodrugs have been approved for clinic application. Although encouraging achievements have been made, the potency of nanomedicines in cancer treatment is far from satisfaction, and one significant reason is the inefficient penetration of nanoparticles into solid tumors. Particle size is one of the most significant features that influence diffusion ability of the drug-delivery system in tumors. Size-shrinkable drug-delivery nanosystems possess a size-switchable property that can achieve passive targeting via the enhanced permeability and retention (EPR) effect and transform into ultrasmall particles in tumors for deep penetration into tumors. The tumor microenvironment is characterized by acidic pH, hypoxia, upregulated levels of enzymes, and a redox environment. In this review, we summarize and analyze the current research progresses and challenges in tumor microenvironment responsive size-shrinkable drug-delivery nanosystems. We further expect to present some meaningful proposals and enlightenments on promoting deep penetration into tumors of nanoparticles.

Advances in Synthesis and Applications of Self-Healing Hydrogels.

BACKGROUND: Hydrogels, a type of three-dimensional (3-D) crosslinked network of polymers containing a high water concentration, have been receiving increasing attention in recent years. Self-healing hydrogels, which can return to their original structure and function after physical damage, are especially attractive. Some self-healable hydrogels have several kinds of properties such as injectability, adhesiveness, and conductivity, which enable them to be used in the manufacturing of drug/cell delivery vehicles, glues, electronic devices, and so on. MAIN BODY: This review will focus on the synthesis and applications of self-healing hydrogels. Their repair mechanisms and potential applications in pharmaceutical, biomedical, and other areas will be introduced. CONCLUSION: Self-healing hydrogels are used in various fields because of their ability to recover. The prospect of self-healing hydrogels is promising, and they may be further developed for various applications.

Food-Grade Pickering Emulsions: Preparation, Stabilization and Applications.

In recent years, Pickering emulsions have emerged as a new method and have attracted much attention in the fields of food sciences. Unlike conventional emulsions, Pickering emulsions are stabilized by solid particles, which can irreversibly adsorb on the oil-water interface to form a dense film to prevent the aggregation of droplets. The research and development of food-grade solid particles are increasingly favored by scientific researchers. Compared with conventional emulsions, Pickering emulsions have many advantages, such as fewer using amounts of emulsifiers, biocompatibility and higher safety, which may offer feasibility to have broad application prospects in a wide range of fields. In this article, we review the preparation methods, stabilization mechanism, degradation of Pickering emulsions. We also summarize its applications in food sciences in recent years and discuss its future prospects and challenges in this work.

Effects of the crystallinity on quercetin loaded the Eudragit L-100 electrospun nanofibers.

The quercetin loaded Eudragit L-100 nanofiber membrane with high ductility and a desired drug release rate was prepared in this work. The morphological characteristics of the Eudragit L-100 nanofibers with different drug loadings amount were observed by scanning electron microscope (SEM). After adding Polyethylene glycol-4000 (PEG-4000), the degree of the fiber breakage decreased and the fiber length increased. Fiber diameter analysis, X-ray diffraction (XRD), thermal analysis (TA) and differential scanning calorimetry (DSC) have demonstrated that the crystallinity of the fiber membrane was significantly reduced after adding PEG-4000. The mechanical property test also showed that the fiber membrane with PEG-4000 had a greater elongation at break. The in vitro release experiments showed that after adding PEG-4000, the drug-loaded fibers showed rapid release at a pH of 7.4. After adopting the strategy of reducing the crystallinity, the ductility of the fiber was enhanced, which could provide a fesibility to enable this nanofiber membrane to be used in sports wound healing treatment. The electrospun Eudragit L-100 nanofiber membranes loaded with quercetin have the potential to be applied in sport wound healing of skin, tissue and joints.

Micro/Nanorobot: A Promising Targeted Drug Delivery System.

Micro/nanorobot, as a research field, has attracted interest in recent years. It has great potential in medical treatment, as it can be applied in targeted drug delivery, surgical operation, disease diagnosis, etc. Differently from traditional drug delivery, which relies on blood circulation to reach the target, the designed micro/nanorobots can move autonomously, which makes it possible to deliver drugs to the hard-to-reach areas. Micro/nanorobots were driven by exogenous power (magnetic fields, light energy, acoustic fields, electric fields, etc.) or endogenous power (chemical reaction energy). Cell-based micro/nanorobots and DNA origami without autonomous movement ability were also introduced in this article. Although micro/nanorobots have excellent prospects, the current research is mainly based on in vitro experiments; in vivo research is still in its infancy. Further biological experiments are required to verify in vivo drug delivery effects of micro/nanorobots. This paper mainly discusses the research status, challenges, and future development of micro/nanorobots.

Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes.

BACKGROUND: Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. RESULTS: In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. CONCLUSIONS: We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA.

RNA interference (RNAi) technology has become a powerful tool in application of unraveling the mechanism of disease and may hold the potential to be developed for clinical uses. Small interfering RNA (siRNA) can bind to target mRNA with high specificity and efficacy and thus inhibit the expression of related protein for the purpose of treatment of diseases. The major challenge for RNAi application is how to improve its stability and bioactivity and therefore deliver therapeutic agents to the target sites with high efficiency and accuracy. PEGylated lipid-based delivery system has been widely used for development of various medicines due to its long circulating half-life time, low toxicity, biocompatibility, and easiness to be scaled up. The PEGylated lipid-based delivery system may also provide platform for targeting delivery of nucleic acids, and some of the research works have moved to the phases for clinical trials. In this review, we introduced the mechanism, major challenges, and strategies to overcome technical barriers of PEGylated lipid-based delivery systems for advanced target delivery of siRNA in vivo. We also summarized recent advance of PEGylated lipid-based siRNA delivery systems and included some successful research works in this field.