A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

A transcriptomics-based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles.

Nickel oxide nanoparticles (NiONPs) are an emerging nanomaterial, which poses a huge threat to the health of workplace population. Nanoparticles induce pulmonary fibrosis, and its mechanisms are associated with noncoding RNAs (ncRNAs). However, ncRNAs and competing endogenous RNA (ceRNA) networks which involved in NiONP-induced pulmonary fibrosis are still unclear. This study aimed to identify ncRNA-related ceRNA networks and investigate the role of the Wnt/ß-catenin pathway in pulmonary fibrosis. Male Wistar rats were intratracheally instilled with 0.015, 0.06, and 0.24 mg/kg NiONPs twice a week for 9 weeks. First, we found there were 93 circularRNAs (circRNAs), 74 microRNAs (miRNAs), 124 long non-coding RNAs (lncRNAs), and 1675 messenger RNAs (mRNAs) differentially expressed through microarray analysis. Second, we constructed ceRNA networks among lncRNAs/circRNAs, miRNAs and mRNAs and identified two ceRNA networks (lncMelttl16/miR-382-5p/Hsd17b7 and circIqch/miR-181d-5p/Stat1) after real time-quantitative polymerase chain reaction (RT-qPCR) validation. Furthermore, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, ncRNAs were found to be involved in biological processes and signaling pathways related to pulmonary fibrosis. KEGG analysis showed that NiONPs activated the Wnt/ß-catenin pathway in rats. In vitro, HFL1 cells were treated with 0, 50, 100, and 200 µg/mL NiONPs for 24 h. We found that NiONPs induced collagen deposition and Wnt/ß-catenin pathway activation. Moreover, a blockade of Wnt/ß-catenin pathway alleviated NiONP-induced collagen deposition. In conclusion, these observations suggested that ncRNAs were crucial in pulmonary fibrosis development and that the Wnt/ß-catenin pathway mediated the deposition of collagen.

Hierarchical Superstructure of Plant Polyphenol and Arginine Surfactant for Long-Lasting and Target-Selective Antimicrobial Application.

Antimicrobial agents are massively used to disinfect the pathogen contaminated surfaces since the Corona Virus Disease 2019 (COVID-19) outbreak. However, their defects of poor durability, strong irritation, and high environmental accumulation are exposed. Herein, a convenient strategy is developed to fabricate long-lasting and target-selective antimicrobial agent with the special hierarchical structure through bottom-up assembly of natural gallic acid with arginine surfactant. The assembly starts from rodlike micelles, further stacking into hexagonal columns and finally interpenetrating into spherical assemblies, which avoid explosive release of antimicrobial units. The assemblies show anti-water washing and high adhesion on various surfaces; and thus, possess highly efficient and broad-spectrum antimicrobial activities even after using up to eleven cycles. Both in vitro and in vivo experiments prove that the assemblies are highly selective in killing pathogens without generating toxicity. The excellent antimicrobial virtues well satisfy the increasing anti-infection demands and the hierarchical assembly exhibits great potential as a clinical candidate.

Bioinspired Screening of Anti-Adhesion Peptides against Blood Proteins for Intravenous Delivery of Nanomaterials.

Nanomaterials (NMs) inevitably adsorb proteins in blood and form "protein corona" upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs.

Multifunctional Gold Nanoparticles in Cancer Diagnosis and Treatment.

Cancer is the second leading cause of death in the world, behind only cardiovascular diseases, and is one of the most serious diseases threatening human health nowadays. Cancer patients' lives are being extended by the use of contemporary medical technologies, such as surgery, radiotherapy, and chemotherapy. However, these treatments are not always effective in extending cancer patients' lives. Simultaneously, these approaches are often accompanied with a series of negative consequences, such as the occurrence of adverse effects and an increased risk of relapse. As a result, the development of a novel cancer-eradication strategy is still required. The emergence of nanomedicine as a promising technology brings a new avenue for the circumvention of limitations of conventional cancer therapies. Gold nanoparticles (AuNPs), in particular, have garnered extensive attention due to their many specific advantages, including customizable size and shape, multiple and useful physicochemical properties, and ease of functionalization. Based on these characteristics, many therapeutic and diagnostic applications of AuNPs have been exploited, particularly for malignant tumors, such as drug and nucleic acid delivery, photodynamic therapy, photothermal therapy, and X-ray-based computed tomography imaging. To leverage the potential of AuNPs, these applications demand a comprehensive and in-depth overview. As a result, we discussed current achievements in AuNPs in anticancer applications in a more methodical manner in this review. Also addressed in depth are the present status of clinical trials, as well as the difficulties that may be encountered when translating some basic findings into the clinic, in order to serve as a reference for future studies.

Self-assembly and cellular distribution of a series of transformable peptides.

Transformable peptides (TPs) are biomedical materials with unique structures and diverse functionalities that have drawn great interest in materials science and nanomedicine. Here, we design a series of TPs with five self-assembling sequences conjugated with the hydrophobic unit bis(pyrene) and the targeting sequence RGD, and study the transformable features induced by ligand (RGD)-receptor (integrin or Ca2+) interactions. TPs are able to self-assemble into nanoparticles or nanosheets and then transform into nano-aggregates or nanofibers induced by RGD-Ca2+ interactions in solution. When TPs are incubated with breast cancer cells expressing integrin receptors on the cell membrane, it is found that they display different cell distributions, including adhesion on the cell membrane, location in the lysosome, or escape from the lysosome to cytoplasm. This study reveals that the self-assembling sequence affects the dynamic self-assembly nanostructures of TPs and the resultant biodistribution in cells.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

Xuefu Zhuyu decoction improves asthma-induced asthenozoospermia based on network pharmacology and in vivo experiment.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-ß-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

LncRNA MEG3 Involved in NiO NPs-Induced Pulmonary Fibrosis via Regulating TGF-ß1-Mediated PI3K/AKT Pathway.

Long noncoding RNA maternally expressed gene 3 (MEG3) involves in fibrotic diseases, but its role in nickel oxide nanoparticles (NiO NPs)-induced pulmonary fibrosis remains unclear. The present study aimed to explore the relationships among MEG3, transforming growth factor-ß1 (TGF-ß1) and phosphoinositide 3-kinase (PI3K)/AKT pathway in NiO NPs-induced pulmonary fibrosis. Wistar rats were intratracheally instilled with NiO NPs twice a week for 9 weeks, and human lung adenocarcinoma epithelial cells (A549 cells) were exposed to NiO NPs for 24 h. The pathological alterations and increased hydroxyproline indicated that NiO NPs caused pulmonary fibrosis in rats. The up-regulated type I collagen (Col-I) suggested that NiO NPs-induced collagen deposition in A549 cells. Meanwhile, NiO NPs could significantly down-regulate MEG3, up-regulate TGF-ß1 and activate PI3K/AKT signaling pathway both in vivo and in vitro. However, we found that the PI3K/AKT pathway activated by NiO NPs could be suppressed by 10 µM TGF-ß1 inhibitor (SB431542) in A549 cells. The protein markers (Col-I, Fibronectin, and alpha-smooth muscle actin) of collagen deposition up-regulated by NiO NPs were reduced by 10 µM PI3K inhibitor (LY294002). Furthermore, we further found that overexpressed MEG3 inhibited the expression of TGF-ß1, resulting in the inactivation of PI3K/AKT pathway and the reduction of collagen formation. In summary, our results validated that MEG3 could arrest NiO NPs-induced pulmonary fibrosis via inhibiting TGF-ß1-mediated PI3K/AKT pathway.

Study on the Mechanism of Jiawei Shengjiang Powder in Improving Male Asthma-Induced Asthenospermia Based on Network Pharmacology and Bioinformatics.

BACKGROUND: Jiawei Shengjiang Powder (JWSJP) is a classical Chinese medicinal formula, which has been widely applied in the treatment of asthma and complications for many years due to its curative effect. AIM: To verify the effect of JWSJP in improving abnormal sperm motility caused by asthma and to explore its potential mechanism. MATERIALS AND METHODS: The active compounds of JWSJP were obtained from high performance liquid chromatography tandem mass spectrometry and the Traditional Chinese Medicine System Pharmacology. The key active components and targets of JWSJP were predicted based on network pharmacological analysis and bioinformatics research. Rats were randomly divided into normal, model and treatment groups. The rat model of allergic asthma was induced by intraperitoneal injection of ovalbumin solution. The experiment judged improvement of semen quality by evaluating sperm motility, and detected the expression of related proteins in testicular tissue of Sprague-Dawley rats by RT-qPCR and Western blot methods. Hematoxylin and eosin (HE) staining was used to observe the changes in testicular tissue structure in rats. RESULTS: Through the analysis of network pharmacology and bioinformatics, it was found that beta-sitosterol, quercetin, gallic acid, pelargonidin and kaempferol were the key active components of Jiawei Shengjiang Powder. Tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS) genes are crucial targets of JWSJP in the treatment of spermatogenic dysfunction caused by acute asthma. After 8 weeks of intervention, compared with the model group, the treatment group had significantly improved sperm motility (P < 0.05). There were significant differences in TNF, IL6, and INS proteins in the treatment group, and the HE staining of testicular tissue structure in the treatment group was significantly improved. CONCLUSION: JWSJP can improve the abnormal sperm motility induced by asthma, and its mechanism may be related to the expression of related proteins and mRNA of TNF, IL6, and INS.