Tailoring biomaterials for vaccine delivery.

Biomaterials are substances that can be injected, implanted, or applied to the surface of tissues in biomedical applications and have the ability to interact with biological systems to initiate therapeutic responses. Biomaterial-based vaccine delivery systems possess robust packaging capabilities, enabling sustained and localized drug release at the target site. Throughout the vaccine delivery process, they can contribute to protecting, stabilizing, and guiding the immunogen while also serving as adjuvants to enhance vaccine efficacy. In this article, we provide a comprehensive review of the contributions of biomaterials to the advancement of vaccine development. We begin by categorizing biomaterial types and properties, detailing their reprocessing strategies, and exploring several common delivery systems, such as polymeric nanoparticles, lipid nanoparticles, hydrogels, and microneedles. Additionally, we investigated how the physicochemical properties and delivery routes of biomaterials influence immune responses. Notably, we delve into the design considerations of biomaterials as vaccine adjuvants, showcasing their application in vaccine development for cancer, acquired immunodeficiency syndrome, influenza, corona virus disease 2019 (COVID-19), tuberculosis, malaria, and hepatitis B. Throughout this review, we highlight successful instances where biomaterials have enhanced vaccine efficacy and discuss the limitations and future directions of biomaterials in vaccine delivery and immunotherapy. This review aims to offer researchers a comprehensive understanding of the application of biomaterials in vaccine development and stimulate further progress in related fields.

Developing hydrogels for gene therapy and tissue engineering.

Hydrogels are a class of highly absorbent and easily modified polymer materials suitable for use as slow-release carriers for drugs. Gene therapy is highly specific and can overcome the limitations of traditional tissue engineering techniques and has significant advantages in tissue repair. However, therapeutic genes are often affected by cellular barriers and enzyme sensitivity, and carrier loading of therapeutic genes is essential. Therapeutic gene hydrogels can well overcome these difficulties. Moreover, gene-therapeutic hydrogels have made considerable progress. This review summarizes the recent research on carrier gene hydrogels for the treatment of tissue damage through a summary of the most current research frontiers. We initially introduce the classification of hydrogels and their cross-linking methods, followed by a detailed overview of the types and modifications of therapeutic genes, a detailed discussion on the loading of therapeutic genes in hydrogels and their characterization features, a summary of the design of hydrogels for therapeutic gene release, and an overview of their applications in tissue engineering. Finally, we provide comments and look forward to the shortcomings and future directions of hydrogels for gene therapy. We hope that this article will provide researchers in related fields with more comprehensive and systematic strategies for tissue engineering repair and further promote the development of the field of hydrogels for gene therapy.

Research progress on the role and mechanism of DNA damage repair in germ cell development.

In the complex and dynamic processes of replication, transcription, and translation of DNA molecules, a large number of replication errors or damage can occur which lead to obstacles in the development process of germ cells and result in a decreased reproductive rate. DNA damage repair has attracted widespread attention due to its important role in the maintenance and regulation of germ cells. This study reports on a systematic review of the role and mechanism of DNA damage repair in germline development. First, the causes, detection methods, and repair methods of DNA damage, and the mechanism of DNA damage repair are summarized. Second, a summary of the causes of abnormal DNA damage repair in germ cells is introduced along with common examples, and the relevant effects of germ cell damage. Third, we introduce the application of drugs related to DNA damage repair in the treatment of reproductive diseases and related surgical treatment of abnormal DNA damage, and summarize various applications of DNA damage repair in germ cells. Finally, a summary and discussion is given of the current deficiencies in DNA damage repair during germ cell development and future research development. The purpose of this paper is to provide researchers engaged in relevant fields with a further systematic understanding of the relevant applications of DNA damage repair in germ cells and to gain inspiration from it to provide new research ideas for related fields.

Current state of knowledge on intelligent-response biological and other macromolecular hydrogels in biomedical engineering: A review.

Because intelligent hydrogels have good biocompatibility, a rapid response, and good degradability as well as a stimulus response mode that is rich, hydrophilic, and similar to the softness and elasticity of living tissue, they have received widespread attention and are widely used in biomedical engineering. In this article, we conduct a systematic review of the use of smart hydrogels in biomedical engineering. First, we introduce the properties and applications of hydrogels and compare the similarities and differences between traditional hydrogels and smart hydrogels. Secondly, we summarize the intelligent hydrogel types, the mechanisms of action used by different hydrogels, and the materials for preparing different types of hydrogels, such as the materials for the preparation of temperature-responsive hydrogels, which mainly include gelatin, carrageenan, agarose, amylose, etc.; summarize the morphologies of different hydrogels, such as films, fibers and microspheres; and summarize the application of smart hydrogels in biomedical engineering, such as for the delivery of proteins, antibiotics, deoxyribonucleic acid, etc. Finally, we summarize the shortcomings of current research and present future prospects for smart hydrogels. The purpose of this paper is to provide researchers engaged in related fields with a systematic review of the application of intelligent hydrogels in biomedical engineering. We hope that they will get some inspiration from this work to provide new directions for the development of related fields.

Expression of IRS2 in the female reproductive system during the estrous cycle in mice.

Insulin receptor substrate 2 (IRS2) participates in reproduction; however, the location and expression of IRS2 in the reproductive system of female mice is not clear. We used real-time quantitative polymerase chain reaction (RT-PCR), western blot and immunohistochemical staining to investigate the expression of IRS2 in the ovary, oviduct and uterus of female mice during the estrous cycle. We found that IRS2 was expressed in all reproductive organs of mouse and that the expression level changed with the estrous phases. The expression of IRS2 in reproductive organs was greatest during estrus.

Multifunctional Silk Fibroin Methacryloyl Microneedle for Diabetic Wound Healing.

Diabetic wound is one of the common complications in diabetic patients, which exhibits chronic, hard-to-heal characteristics. The healing process of wounds is impaired by several factors, including excessive oxidative stress, blocked angiogenesis, and bacterial infection. The therapeutic effects of traditional microneedle patches remain not satisfactory, due to their difficulty simultaneously targeting multiple targets to treat diabetic wounds. As such, there is an urgent need to develop a multifunctional microneedle (MN) patch for promoting the healing of diabetic wounds. A multifunctional MN patch with antioxidant, proangiogenesis, and antibacterial capacities was fabricated to target the pathogenesis of diabetic wounds. Silk fibroin methacryloyl, which has excellent biocompatibility, stable mechanical properties, and well processability, and is selected as the base material for multifunctional MN patches. Prussian blue nanozymes (PBNs) and vascular endothelial growth factor (VEGF) are encapsulated in tips of MN patches, Polymyxin is encapsulated in base layers of MN patches. Based on synergic properties of these components, multifunctional MN patches exhibit excellent biocompatibility, drug-sustained release, proangiogenesis, antioxidant, and antibacterial properties. The developed multifunctional MN patches accelerate diabetic wound healing, providing a potential therapeutic approach.

Natural Materials for 3D Printing and Their Applications.

In recent years, 3D printing has gradually become a well-known new topic and a research hotspot. At the same time, the advent of 3D printing is inseparable from the preparation of bio-ink. Natural materials have the advantages of low toxicity or even non-toxicity, there being abundant raw materials, easy processing and modification, excellent mechanical properties, good biocompatibility, and high cell activity, making them very suitable for the preparation of bio-ink. With the help of 3D printing technology, the prepared materials and scaffolds can be widely used in tissue engineering and other fields. Firstly, we introduce the natural materials and their properties for 3D printing and summarize the physical and chemical properties of these natural materials and their applications in tissue engineering after modification. Secondly, we discuss the modification methods used for 3D printing materials, including physical, chemical, and protein self-assembly methods. We also discuss the method of 3D printing. Then, we summarize the application of natural materials for 3D printing in tissue engineering, skin tissue, cartilage tissue, bone tissue, and vascular tissue. Finally, we also express some views on the research and application of these natural materials.

Total flavonoids of Abrus cantoniensis inhibit CD14/TLR4/NF-κB/MAPK pathway expression and improve gut microbiota disorders to reduce lipopolysaccharide-induced mastitis in mice.

Established a model of lipopolysaccharide (LPS)-induced mastitis in mice, pathological sections and myeloperoxidase were used to detect the degree of tissue damage, enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of pro-inflammatory cytokines, meanwhile fluorescence quantitative PCR experiments were performed to detect the mRNA expression of CD14/TLR4/NF-κB/MAPK signalling pathway, and the faeces of mice were collected for 16S measurement of flora. The results showed that Abrus cantoniensis total flavonoids (ATF) could significantly reduce the damage of LPS on mammary tissue in mice and inhibit the secretion of inflammatory factors such as TNF-α, IL-1ß and IL-6. At the mRNA level, ATF inhibited the expression of CD14/TLR4/NF-κB/MAPK pathway and enhanced the expression of tight junction proteins in the blood-milk barrier. In the results of the intestinal flora assay, ATF were found to be able to regulate the relative abundance of the dominant flora from the phylum level to the genus level, restoring LPS-induced gut microbial dysbiosis. In summary, ATF attenuated the inflammatory response of LPS on mouse mammary gland by inhibiting the expression of CD14/TLR4/NF-κB/MAPK pathway, enhancing the expression of tight junction proteins and restoring LPS-induced gut microbial dysbiosis. This suggests that ATF could be a potential herbal remedy for mastitis.

Genetic Variation Analysis of Porcine Circovirus Type 4 in South China in 2019 to 2021.

Porcine circovirus type 4 (PCV4) is a novel virus associated with porcine dermatitis and nephropathy syndrome (PDNS)-like signs identified firstly in China in 2019. However, the details of the molecular epidemiology of PCV4 are unclear at this time. A total of forty-two related sequences were selected from the GenBank database to explore the spread of PCV4 and its rule in genetic evolution. Of the selected strains, 41 were from south China in 2019 to 2021 and the other was a foreign representative strain. Phylogenetic tree construction, nucleotide and amino acid (aa) sequence alignment, gene recombination and antigen structure prediction were performed on the collected sequences using bioinformatics softwares. The 42 PCV4 strains were divided into two subgenotypes: PCV4a (35/42) and PCV4b (7/42), according to the constructed genetic evolution tree. PCV4a is the main epidemic strain, and it can be further divided into two different gene clusters: PCV4a-1 (22/35) and PCV4a-2 (13/35). The pairwise comparison analysis showed that the complete genome sequence similarity of the 42 PCV4 strains ranged between 97.9% and 100%, and the aa sequences of the Cap proteins of 42 PCV4 strains had three major heterogenic or hypervariable regions-27-28, 96 and 212-all located near the antigenic epitope of the Cap protein. The results of this study can provide some basis for further studying the spread and epidemic growth of PCV4, and the prevention and control of PCV4 infection in China.

Research Progress on Emerging Polysaccharide Materials Applied in Tissue Engineering.

The development and application of polysaccharide materials are popular areas of research. Emerging polysaccharide materials have been widely used in tissue engineering fields such as in skin trauma, bone defects, cartilage repair and arthritis due to their stability, good biocompatibility and reproducibility. This paper reviewed the recent progress of the application of polysaccharide materials in tissue engineering. Firstly, we introduced polysaccharide materials and their derivatives and summarized the physicochemical properties of polysaccharide materials and their application in tissue engineering after modification. Secondly, we introduced the processing methods of polysaccharide materials, including the processing of polysaccharides into amorphous hydrogels, microspheres and membranes. Then, we summarized the application of polysaccharide materials in tissue engineering. Finally, some views on the research and application of polysaccharide materials are presented. The purpose of this review was to summarize the current research progress on polysaccharide materials with special attention paid to the application of polysaccharide materials in tissue engineering.

Progress in the application of sustained-release drug microspheres in tissue engineering.

Sustained-release drug-loaded microspheres provide a long-acting sustained release, with targeted and other effects. There are many types of sustained-release drug microspheres and various preparation methods, and they are easy to operate. For these reasons, they have attracted widespread interest and are widely used in tissue engineering and other fields. In this paper, we provide a systematic review of the application of sustained-release drug microspheres in tissue engineering. First, we introduce this new type of drug delivery system (sustained-release drug carriers), describe the types of sustained-release drug microspheres, and summarize the characteristics of different microspheres. Second, we summarize the preparation methods of sustained-release drug microspheres and summarize the materials required for preparing microspheres. Third, various applications of sustained-release drug microspheres in tissue engineering are summarized. Finally, we summarize the shortcomings and discuss future prospects in the development of sustained-release drug microspheres. The purpose of this paper was to provide a further systematic understanding of the application of sustained-release drug microspheres in tissue engineering for the personnel engaged in related fields and to provide inspiration and new ideas for studies in related fields.

Current Understanding of Hydrogel for Drug Release and Tissue Engineering.

Due to their good absorption, satisfactory biocompatibility, and high safety, hydrogels have been widely used in the field of biomedicine, including for drug delivery and tissue regeneration. In this review, we introduce the characteristics and crosslinking methods of natural and synthetic hydrogels. Then, we highlight the design and principle of intelligent hydrogels (i.e., responsive hydrogels) used for drug release. Moreover, we introduce the application of the application of hydrogels in drug release and tissue engineering, and the limitations and research directions of hydrogel in drug release and tissue engineering are also considered. We hope that this review can provide a reference for follow-up studies in related fields.

Current Understanding of the Applications of Photocrosslinked Hydrogels in Biomedical Engineering.

Hydrogel materials have great application value in biomedical engineering. Among them, photocrosslinked hydrogels have attracted much attention due to their variety and simple convenient preparation methods. Here, we provide a systematic review of the biomedical-engineering applications of photocrosslinked hydrogels. First, we introduce the types of photocrosslinked hydrogel monomers, and the methods for preparation of photocrosslinked hydrogels with different morphologies are summarized. Subsequently, various biomedical applications of photocrosslinked hydrogels are reviewed. Finally, some shortcomings and development directions for photocrosslinked hydrogels are considered and proposed. This paper is designed to give researchers in related fields a systematic understanding of photocrosslinked hydrogels and provide inspiration to seek new development directions for studies of photocrosslinked hydrogels or related materials.

Angiogenic Microspheres for the Treatment of a Thin Endometrium.

The poor vascular development of an endometrium is the key cause of a thin endometrium due to the vascular endothelial growth factor (VEGF) decreasing in the glandular epithelium. Hence, inducing angiogenesis is an effective strategy for thin endometrium treatment in clinic. Herein, we developed a novel angiogenic hydrogel microsphere based on methacrylated hyaluronic acid (HAMA) loaded with VEGF for the treatment of a thin endometrium by a microfluidic electrospray technique. The generated HAMA microspheres with uniform size, porous structure, and satisfactory biocompatibility increased the drug-loading ability and controlled the drug-release rate by adjusting the hydrogel concentration. Besides, the HAMA microspheres loaded with VEGF showed satisfactory biocompatibility and promoted blood vessel formation in vitro. More importantly, the combination of HA and VEGF promoted new blood vessels and endometrial regeneration of a thin endometrium in vivo. Therefore, the combination of HA and VEGF would be conducive to the development of a drug-delivery microsphere with excellent biocompatibility and therapeutic effect for thin endometrium treatment and other biomedical applications.

Curcumin Ameliorates Palmitic Acid-Induced Saos-2 Cell Apoptosis Via Inhibiting Oxidative Stress and Autophagy.

OBJECTIVES: We aimed to determine the effects of curcumin on palmitic acid- (PA-) induced human osteoblast-like Saos-2 cell apoptosis and to explore the potential molecular mechanisms in vitro level. METHODS: Saos-2 cell were cultured with PA with or without curcumin, N-acetylcysteine (NAC, anti-oxidant), 3-methyladenine (3-MA, autophagy inhibitor) AY-22989 (autophagy agonist) or H2O2. Then, the effects of PA alone or combined with curcumin on viability, apoptosis, oxidative stress, and autophagy in were detected by CCK-8, flow cytometry assay and western blot. RESULTS: We found that autophagy was induced, oxidative stress was activated, and apoptosis was promoted in PA-induced Saos-2 cells. Curcumin inhibited PA-induced oxidative stress, autophagy, and apoptosis in Saos-2 cells. NAC successfully attenuated oxidative stress and apoptosis, and 3-MA attenuated oxidative stress and apoptosis in palmitate-induced Saos-2 cells. Interestingly, NAC inhibited PA-induced autophagy, but 3-MA had no obvious effects on oxidative stress in PA-treated Saos-2 cells. In addition, curcumin inhibited H2O2 (oxidative stress agonist)-induced oxidative stress, autophagy, and apoptosis, but curcumin had no obvious effect on AY-22989 (autophagy agonist)-induced autophagy and apoptosis. CONCLUSION: The present study demonstrated that oxidative stress is an inducer of autophagy and that curcumin can attenuate excess autophagy and cell apoptosis by inhibiting oxidative stress in PA-induced Saos-2 cells.

Advances in Research on the Toxicological Effects of Selenium.

Selenium is a trace element necessary for the growth of organisms. Moreover, selenium supplementation can improve the immunity and fertility of the body, as well as its ability to resist oxidation, tumors, heavy metals, and pathogenic microorganisms. However, owing to the duality of selenium, excessive selenium supplementation can cause certain toxic effects on the growth and development of the body and may even result in death in severe cases. At present, increasing attention is being paid to the development and utilization of selenium as a micronutrient, but its potential toxicity tends to be neglected. This study systematically reviews recent research on the toxicological effects of selenium, aiming to provide theoretical references for selenium toxicology-related research and theoretical support for the development of selenium-containing drugs, selenium-enriched dietary supplements, and selenium-enriched foods.

Porcine circovirus type 2 exploits cap to inhibit PKR activation through interaction with Hsp40.

Porcine circovirus type 2 is the main pathogen of porcine circovirus disease, which has caused enormous economic losses to the pig industry worldwide. The PKR signaling pathway is important for the cellular antiviral response, but its role in the process of PCV2 infection is unknown. In this study, we first found that dsRNA was produced and that PKR was activated in PCV2 infection. However, interestingly, the activation of PKR was inhibited when the Cap protein was exogenously expressed in PAMs, and this inhibition was reversed by the expression of DNAJC7. The interaction between Cap and DNAJC7 was confirmed by laser confocal microscopy, coimmunoprecipitation and GST pull-down, and it was found that PCV2 infection or the expression of Cap protein could induce DNAJC7 to migrate to the nucleus and release P58IPK, an inhibitor of PKR activation. Downregulating the expression of DNAJC7 by a specific inhibitor or recombinant lentivirus-mediated shRNA, inhibited the replication of the PCV2 genome and the production of virions, which was consistent with the increase of DNAJC7 expression in multiple tissues of weaned piglets infected with PCV2. These data indicate that although PKR was activated by PCV2 infection, the activation was inhibited by Cap through an interaction with DNAJC7. These results help to understand the molecular mechanism of immune escape after PCV2 infection.

Genomic analysis of porcine circovirus type 2 from southern China.

BACKGROUND: Porcine circovirus type 2 (PCV2) is recognized as virulent porcine pathogen and has been linked to porcine circovirus diseases (PCVD). However, there remain many unknowns regarding the spread and epidemic growth of PCV2. METHODS: To assess the genetic diversity of PCV2 in the southern China, a total of 92 sequences of PCV2 strains from this region were retrieved from GenBank and were subjected to amino acid variation and phylogenetic analyses together with 28 representative sequences, based on the sequence of the ORF2 gene, from different swine-producing countries. RESULTS: All 92 PCV2 strains shared between 93.7% and 100% sequence similarity and could be divided into four genotypes (PCV2a, PCV2b, PCV2d and PCV2h), of which PCV2d had surpassed PCV2b and became the most prevalent PCV2 genotype in this region. Alignment of the deduced amino acid sequences of the capsid protein revealed that the obtained PCV2 strains possess two major heterogenic regions/hypervariable regions (positions 52-68 and 185-191), which were within or close to the epitopic regions in the capsid (Cap) protein. Meanwhile, the 92 PCV2 sequences also show evidence of at least five unique recombination events. CONCLUSION: The data in this study indicate that the PCV2 strains in the southern China are undergoing constant genetic variation and that the predominant strain and its antigenic epitopes in this area have been gradually changing in recent years.

miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

MicroRNAs (miRNAs) regulate the functions of granulosa cells by interacting with their target mRNAs. Insulin receptor substrate 2 (IRS2) is one of the targets of miR-431 and can be regulated by ovarian hormones. However, the role of miR-431 and the associated signal transduction pathway in ovarian development has not been studied previously. In this study, we first analyzed the expression of miR-431 and IRS2 following stimulation with pregnant mare serum gonadotropin (PMSG) during the estrous cycle or different stages of ovarian development in mice. Subsequently, we investigated the role, function, and signaling pathway of miR-431 in the human granulosa cell line, COV434. The results showed that follicle stimulating hormone (FSH) gradually decreased miR-431 levels, induced IRS2, and promoted pAKT expression. Moreover, miR-431 overexpression and IRS2 knockdown attenuated AKT activation, inhibited cell proliferation, and decreased estradiol (E2) and progesterone (P4) synthesis. Further, luciferase reporter assay demonstrated that IRS2 was a direct target of miR-431. In conclusion, this study demonstrated that miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

Lycium barbarum polysaccharide enhances development of previously-cryopreserved murine two-cell embryos via restoration of mitochondrial function and down-regulated generation of reactive oxygen species.

Lycium barbarum polysaccharide (LBP) exhibits multiple pharmacological and biological effects, including displaying antioxidant and cytoprotective properties. The current study investigated the effects of LBP-supplemented culture medium on mitochondrial distribution, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) production, mitochondrial deoxyribonucleic acid (mtDNA) copy number, reactive oxygen species (ROS) accumulation, and development of previously-cryopreserved murine two-cell embryos. Results indicate that LBP enhances development of such embryos, and that potential mechanisms include: (1) mitochondrial function enhancement via altering mitochondrial distribution and increasing MMP, ATP production, mtDNA copy number, and expression of genes involved in mitochondrial biogenesis and energy metabolism (NAD-dependent deacetyltransferase sirtuin-1 (SIRT1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK)); (2) down-regulation of ROS generation and enhanced expression of the antioxidant genes glutathione peroxidase 4 (GPX4) and superoxide dismutase 1 (SOD1), thereby increasing embryo oxidative stress tolerance; and (3) increased expression of B-cell lymphoma-2 (BCL2), a critical gene for cell survival and embryo development. These results demonstrate that LBP improves development of previously-cryopreserved murine two-cell embryos via restoration of mitochondrial function and down-regulated generation of ROS.