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MicroRNAs (miRNAs), a class of single-stranded non-coding RNA of about 22 nucleotides, are potent regulators of gene expression existing in both plants and animals. Recent studies showed that plant miRNAs could enter mammalian bloodstream via gastrointestinal tract, through which access a variety of tissues and cells of recipients to exert therapeutic effects. This intriguing phenomenon indicates that miRNAs of diet/plant origin may act as a new class of bioactive ingredients communicating with mammalian systems. In this review, in order to pinpoint the reason underlying discrepancies of miRNAs transmission from diet/plant to animals, the pathways that generate miRNAs and machineries involved in the functions of miRNAs in both kingdoms were outlined and compared. Then, the current controversies concerning cross-kingdom regulations and the potential mechanisms responsible for absorption and transfer of diet/plant-derived miRNAs were interpreted. Furthermore, the hormone-like action of miRNAs and the intricate interplay between miRNAs and hormones were implicated. Finally, how these findings may impact nutrition and medicine were briefly discussed.

Virus-like particle (VLP) is a self-assembled nanostructure incorporating key viral structural proteins. VLP resembles molecular and morphological features of authentic viruses but is non-infectious and non-replicating due to lack of genetic materials. Successful applications of VLP has been shown in vaccinological and virological research. As an accessibly safe and relevant substitute of naturally pathogenic viruses, the construction of SARS-CoV-2 VLPs is much in demand in the ongoing fight against 2019 Coronavirus disease (COVID-19) pandemics. In the current study, using mammalian expression system, which is advantageous in maintaining correct protein glycosylation patterns, we efficiently constructed SARS-CoV-2 VLPs. We showed that among four SARS-CoV-2 structural proteins, expression of membrane protein (M) and small envelope protein (E) are essential for efficient formation and release of SARS-CoV-2 VLPs. Moreover, the corona-like structure presented in SARS-CoV-2 VLPs from Vero E6 cells is more stable and unified, as compared to those from HEK-293T cells. Our data demonstrate that SARS-CoV-2 VLPs possess molecular and morphological properties of native virion particles, which endow such VLPs with a promising vaccine candidate and a powerful tool for the research of SARS-CoV-2.Virus-like particle (VLP) is a self-assembled nanostructure incorporating key viral structural proteins. VLP resembles molecular and morphological features of authentic viruses but is non-infectious and non-replicating due to lack of genetic materials. Successful applications of VLP has been shown in vaccinological and virological research. As an accessibly safe and relevant substitute of naturally pathogenic viruses, the construction of SARS-CoV-2 VLPs is much in demand in the ongoing fight against 2019 Coronavirus disease (COVID-19) pandemics. In the current study, using mammalian expression system, which is advantageous in maintaining correct protein glycosylation patterns, we efficiently constructed SARS-CoV-2 VLPs. We showed that among four SARS-CoV-2 structural proteins, expression of membrane protein (M) and small envelope protein (E) are essential for efficient formation and release of SARS-CoV-2 VLPs. Moreover, the corona-like structure presented in SARS-CoV-2 VLPs from Vero E6 cells is more stable and unified, as compared to those from HEK-293T cells. Our data demonstrate that SARS-CoV-2 VLPs possess molecular and morphological properties of native virion particles, which endow such VLPs with a promising vaccine candidate and a powerful tool for the research of SARS-CoV-2.

The challenges associated with prolonged healing or non-healing of chronic diabetic wounds contribute significantly to the increased incidence of lower limb amputation. A pivotal factor in the impediment of healing is the reduced production of endogenous nitric oxide (NO) due to the hyperglycemic microenvironment typical of chronic diabetes. While both endogenous and exogenous NO have been shown to promote the healing process of diabetic wounds, the direct application of NO in wound management is limited due to its gaseous nature and the risk of explosive release. This review summarizes recent advances of nanodressings incorporating NO donors in the treatment of diabetic wounds, detailing the specific conditions under which these nanodressings facilitate NO release, with a focus on the beneficial effects of NO, strategies for its supplementation, and the challenges encountered in the clinical translation of NO donors as a clinically viable nanomedicine in the context of improving diabetic wound healing. Graphical Abstract

Coronaviruses (CoVs) are a class of respiratory viruses with the potential to cause severe respiratory diseases by infecting cells of the upper respiratory tract, bronchial epithelium, and lung. The airway cilia are distributed on the surface of respiratory epithelial cells, forming the first point of contact between the host and the inhaled coronaviruses. The function of the airway cilia is to oscillate and sense, thereby defending against and removing pathogens to maintain the cleanliness and patency of the respiratory tract. Following infection of the respiratory tract, coronaviruses exploit the cilia to invade and replicate in epithelial cells while also damaging the cilia to facilitate the spread and exacerbation of respiratory diseases. It is therefore imperative to investigate the interactions between coronaviruses and respiratory cilia, as well as to elucidate the functional mechanism of respiratory cilia following coronavirus invasion, in order to develop effective strategies for the prevention and treatment of respiratory viral infections. This review commences with an overview of the fundamental characteristics of airway cilia, and then, based on the interplay between airway cilia and coronavirus infection, we propose that ciliary protection and restoration may represent potential therapeutic approaches in emerging and re-emerging coronavirus pandemics.

Psoriasis is a chronic, relapsing, and refractory immune-mediated skin disease with the etiology and pharmaceutical targets remaining unsatisfactorily addressed. Topical herbal-derived compounds, such as tryptanthrin (Tryp), have been considered as an alternative therapy for psoriasis due to their lower costs and fewer side effects compared to other therapies. However, the effectiveness of topically administered drugs is substantially limited by the thickened pathological skin barrier and the low bioavailability of drugs in the deeper layers of the lesion. Ethosomes, being a novel phospholipid-based vesicle system with high content of ethanol, have been implicated in enhancing topical drug absorption and restoring psoriatic lesions. In this study, taking advantages of ethosomes as a soft and malleable drug carrier, we constructed the Tryp-loaded ethosome (Tryp-ES) through a one-step microfluidics-based technique. The optimal formulation of Tryp-ES was achieved by adding amino-acid-derived surfactant sodium lauroyl glutamate, and Tryp-ES exhibited homogeneous particle size and favorable stability at room temperature. In vitro evaluations showed that Tryp of Tryp-ES could be easily internalized into cells and accumulated in cell nuclei, hence inhibited the abnormally proliferated keratinocytes by inducing apoptosis. In vivo and in vitro assessment using psoritic skin of mice revealed that Tryp-ES had preferred skin retention and permeation of loaded drugs within the initial 1 h of topical administration, which could be attributed to transient disintegrations of cell membranes by ethosomes, thus improved cellular fluidity and permeability. Notably, a synergistic effect of ethosomes and Tryp was found in psoriatic mice. Tryp-ES-treated mice showed substantially ameliorated symptoms of psoriasis and reduced pathological alterations due to hyperplasia, inflammation and angiogenesis, without detectable local or systemic toxicities. Interestingly, lipidomics analysis confirmed that the supplementation of phospholipids, as in the form of ethosome vehicles, was an alterantive strategy to relieve psoriatic pathologies. Taken together, this study provides a novel impact for ethosomal topical delivery of Tryp and underlines their potential as an effective therapy for the management of psoriasis.

The success of mesenchymal stem cell transplantation is highly dependent on their survival and controlled fate regulation. This study demonstrates that dual-delivery of connective tissue growth factor (CTGF) and fibroblast growth factor 2 (FGF-2) from a core-shell fiber of Silk Fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene oxide (SF/PLCL-PEO) enhanced fibrogenic lineage differentiation of MSCs. The core-shell structure was confirmed by transmission electron microscopy (TEM), fluorescence microscopy and attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy. A sequential release of FGF-2 and CTGF was successfully achieved in this manner. FGF-2 plays an important role in stem cell proliferation and, meanwhile when accompanied with CTGF, has a slightly additive effect on fibrogenic differentiation of MSCs, whereas CTGF promotes fibrogenesis and alleviates osteogenesis, chondrogenesis and adipogenesis.

Inspired by the skin structure, an asymmetric wettability tri-layer nanofiber membrane (TNM) consisting of hydrophilic inner layer loaded with lidocaine hydrochloride (LID), hydrophobic middle layer with ciprofloxacin (CIP) and hydrophobic outer layer has been created. The hydrophobic outer layer endows the TNM with waterproof function and anti-adhesion from contaminants. The hydrophobic middle layer with CIP preserves long-term inhibition of bacteria growth and the hydrophilic inner layer with LID possesses optimal water-absorbing capacity and air permeability. The TNM dramatically elevates the water contact angles from 10° (inner layer) to 120° (outer layer), indicating an asymmetric wettability, which could directionally transport wound exudate within the materials and meanwhile maintain a comfortable and moist environment to promote wound healing. Furthermore, the sequential release of LID and CIP could relieve pain rapidly and achieve antibacterial effect in the long run, respectively. In addition, the TNM shows superior biocompatibility towards L929 ​cells. The in vivo results show the TNM could prevent infection, accelerate epithelial regeneration and significantly accelerate wound healing. This study indicates the developed TNM with asymmetrical wettability and synergetic drug release shows great potential as a wound dressing in clinical application.

Psoriasis is a chronic, immune-mediated skin disorder involving hyperproliferation of the keratinocytes in the epidermis. As complex as its pathophysiology, the optimal treatment for psoriasis remains unsatisfactorily addressed. Though systemic administration of biological agents has made an impressive stride in moderate-to-severe psoriasis, a considerable portion of psoriatic conditions were left unresolved, mainly due to adverse effects from systemic drug administration or insufficient drug delivery across a highly packed stratum corneum via topical therapies. Along with the advances in nanotechnologies, the incorporation of nanomaterials as topical drug carriers opens an obvious prospect for the development of antipsoriatic topicals. Hence, this review aims to distinguish the benefits and weaknesses of individual nanostructures when applied as topical antipsoriatics in preclinical psoriatic models. In view of specific features of each nanostructure, we propose that a proper combination of distinctive nanomaterials according to the physicochemical properties of loaded drugs and clinical features of psoriatic patients is becoming a promising option that potentially drives the translation of nanomaterials from bench to bedside with improved transdermal drug delivery and consequently therapeutic effects.

Indigo Naturalis (IN) has been traditionally used for psoriasis treatment. We developed an IN-poly (ε -caprolactone, PCL)/poly (ethylene oxide, PEO) nanofibrous patch using electrospinning technology. Preliminary studies demonstrated its potential to reduces keratinocyte proliferation, inflammation, and neovascularization, addressing limitations of conventional IN formulations such as poor absorption and skin staining. To evaluate the safety and efficacy of the IN-PCL/PEO patch for chronic plaque psoriasis. The clinical trial included 36 patients diagnosed with chronic plaque psoriasis. Two symmetrical psoriatic lesions from each eligible patient were selected by dermatologists and randomly assigned to receive either calcipotriol ointment (control group) or IN-PCL/PEO nanofibrous patch (test group) for 4 weeks. Primary outcomes included Psoriasis Area and Severity Index (PASI), while secondary outcomes assessed Patient Global Assessment (PGA), skin irritation, and patient satisfaction. Safety was monitored via blood, urine, and liver/kidney function tests. 30 subjects completed the treatment trial with both IN and CA. In the test group (n = 30), PASI scores decreased from 6.30 ± 2.23 to 2.13 ± 1.57 ( < 0.001). Within this group, 90.0% (27/30) achieved PASI 50% and 43.3% (13/30) achieved PASI 75. No skin irritation cases were reported (0.0%). While PASI scores decreased from 6.23 ± 2.27 to 2.23 ± 1.50 ( < 0.001) in the control group, 86.7% (26/30) achieved PASI 50% and 33.3% (10/30) achieved PASI 75, with 6.7% (2/30) experiencing irritation. All safety parameters remained within standard reference ranges. The IN-PCL/PEO patch demonstrated efficacy comparable to calcipotriol ointment, with improved safety and tolerability, suggesting its potential as an alternative psoriasis treatment.

The novel coronavirus disease 2019 (COVID-19) has become a matter of international concern as the disease is spreading exponentially. Statistics showed that infected patients in China who received combined treatment of Traditional Chinese Medicine and modern medicine exhibited lower fatality rate and relatively better clinical outcomes. Both Lian-Hua-Qing-Wen Capsule (LHQWC) and Jin-Hua-Qing-Gan Granule (JHQGG) have been recommended by China Food and Drug Administration for the treatment of COVID-19 and have played a vital role in the prevention of a variety of viral infections. Here, we desired to analyze the broad-spectrum anti-viral capacities of LHQWC and JHQGG, and to compare their pharmacological functions for rational clinical applications. Based on literature mining, we found that both LHQWC and JHQGG were endowed with multiple antiviral activities by both targeting viral life cycle and regulating host immune responses and inflammation. In addition, from literature analyzed, JHQGG is more potent in modulating viral life cycle, whereas LHQWC exhibits better efficacies in regulating host anti-viral responses. When translating into clinical applications, oral administration of LHQWC could be more beneficial for patients with insufficient immune functions or for patients with alleviated symptoms after treatment with JHQGG.