AbstractInfections caused by drug-resistant bacteria are major health concerns worldwide. We successfully synthesized cephradine gold nanoparticles (Ceph-Au NPs) and cephradine silver nanoparticles (Ceph-Ag NPs) and compared their efficacy against resistant human pathogens. X-Ray diffraction (XRD), Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) results showed that average particle size of Ceph-Au NPs and Ceph-Ag NPs were 7 and 12 nm, respectively. Fourier Transform Infra-red spectroscopy (FTIR) spectra revealed the conjugation of –NH2 and –OH functional moieties with the nanoparticle (NP) surfaces. These NPs significantly inhibited the biofilm of Streptococcus mutans (S. mutans) and methicillin-resistant Staphylococcus aureus (MRSA) in the range of 61.25–250 µg/mL. Ceph-Au NPs are more active than Ceph-Ag NPs and can be used to treat the diseases associated with MRSA and S. mutans.

AbstractIn photodynamic therapy (PDT), internalization and uptake of the photosensitizer (PS) by the cells is a passive process that relies on the enhanced permeability and retention (EPR) effect of tumour tissues due to their vasculature, increased LDL receptors, and decreased lymphatic drainage in vivo. But as worries about PDT resistance grow, using passive techniques to administer PSs is becoming less and less viable. According to reported resistance mechanisms, it is necessary to improve PS delivery by changing PS absorption and bioavailability in order to enhance the therapeutic outcome. Therefore, in this study, a multifunctional photosensitizing agent with specific monoclonal antibodies (mAbs) to E6 oncoproteins was developed for PDT of human papillomavirus (HPV)-transformed cancer cells. Using PEGylated Gold Nanoparticles (PEGy-AuNP) at the core, anti-E6 mAbs and phthalocyanines were bound together. This compound demonstrated enhanced internalization of PS, resulting in enhanced PDT effects. In spite of being demonstrated in vitro, the substance in this work is intended for in vivo application, and conclusions are drawn to suggest possible outcomes for in vivo models based on observed data. By making PSs more bioavailable, facilitating their entry into cells, and preventing efflux through intracellular binding, this strategy may reduce cellular resistance to PDT.

Published in Artificial Cells, Nanomedicine, and Biotechnology: An International Journal (Vol. 50, No. 1, 2022)

Published in Artificial Cells, Nanomedicine, and Biotechnology: An International Journal (Vol. 50, No. 1, 2022)

AbstractThe present research was carried out to look into therapeutic insight of biosynthesized silver nanoparticles (AgNPs) by leaf extract of Byttneria herbacea Roxb (BH). The analysis of biosynthesized BH-AgNPs by UV-visible spectroscopy shows an intense surface plasmon resonance (SPR) peak at 422 nm initially and 437 nm after 30 min which certainly reveals the formation of BH-AgNPs. Fourier Infra-red Spectroscopy (FT-IR) reveals that BH-AgNPs are biosynthesized by using different bioactive compounds like O-H stretch of free hydroxyl alcohol and phenols, N-H bond of primary amines present in the leaf extract. Transmission Electron Microscope (TEM) analysis revealed that BH-AgNPs are almost spherical in nature with an average size range from of 2 nm to 12 nm. The particle size analysis by Dynamic Light Scattering (DLS) reveals that the BH-AgNPs are poly-dispersed in nature with an average size of 8 nm ± 2 nm, with a negative zeta potential value of −21 mV which reveals the biosynthesized BH-AgNPs are very stable. The BH-AgNPs (Byttneria herbacea -AgNPs) revealed excellent free radical scavenging activity and exceptional antimicrobial activity. The anti-proliferative and cytotoxic studies in KB oral cancer cells revealed biosynthesized BH-AgNPs can employ as future novel therapeutic agents in cancer treatment and other biomedical applications.

AbstractAs the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.

AbstractWe intended to identify favourable metabolite(s) and pharmacological mechanism(s) of gut microbiota (GM) for liver regeneration (LR) through network pharmacology. We utilized the gutMGene database to obtain metabolites of GM, and targets associated with metabolites as well as LR-related targets were identified using public databases. Furthermore, we performed a molecular docking assay on the active metabolite(s) and target(s) to verify the network pharmacological concept. We mined a total of 208 metabolites in the gutMGene database and selected 668 targets from the SEA (1,256 targets) and STP (947 targets) databases. Finally, 13 targets were identified between 61 targets and the gutMGene database (243 targets). Protein–protein interaction network analysis showed that AKT1 is a hub target correlated with 12 additional targets. In this study, we describe the potential microbe from the microbiota (E. coli), chemokine signalling pathway, AKT1 and myricetin that accelerate LR, providing scientific evidence for further clinical trials.

AbstractTumour development is not only an independent event of genetic mutation and overgrowth of tumour cells but is the result of a synergistic interaction between a malignant tumour and its surrounding tumour stromal microenvironment. In this paper, we address the shortcomings of current tumour therapy by focussing on the tumour itself and the surrounding microenvironment to achieve a two-pronged targeting model. In this paper, a dual-targeting, pH/reactive oxygen species (ROS) sensitive nano-drug delivery system for tumour cells and CAFs was designed. A hyaluronic acid (HA) with CD44 receptor targeting on the surface of tumour cells was selected as the main carrier material, and a dipeptide Z-glycine-proline (ZGP) with specific targeting of fibroblast activating protein (FAP) on the surface of CAFs was modified on HA to achieve precise targeting of CAFs, open the physical barrier of tumour cells and improve the deep penetration effect of the tumour, while introducing thioketone bond and ketone condensation bond to take advantage of the highly reactive ROS and low pH microenvironment at the tumour site to achieve chemical bond breaking of nano micelles encapsulating paclitaxel (PTX), drug release, and thus drug aggregation at the tumour site and improved bioavailability of the drug.

Published in Artificial Cells, Nanomedicine, and Biotechnology: An International Journal (Vol. 50, No. 1, 2022)

AbstractThe small diameter crystalline silica is inhaled into the lung and cannot be cleared. As a result, the patient suffers from silicosis, a lung disease for which there is no effective treatment except lung transplantation. The aim of this study is to reveal the histological, cytological and metabolic characteristics of mice with pulmonary fibrosis induced by different doses of silica, and to provide an ideal animal model for drug development and disease research of pulmonary fibrosis. The experimental mice were divided into five groups. The mice were sacrificed 42 d later by nasal inhalation of normal saline and suspension containing silica 1 mg, 2 mg, 4 mg and 8 mg. Lung specimens and bronchoalveolar lavage fluid (BALF) were collected for histological and cytological examination. Carotid blood was collected and centrifuged to obtain serum for UHPLC-QE-MS non-target metabolomics detection. Compared with the normal control group, except 1 mg silica group, the other dosage groups showed different degree of disease characteristics. Metabolomics analysis showed that arginine and proline metabolism, pentose phosphate pathway, histidine metabolism, cysteine and methionine metabolism, ascorbic acid and aldoglucose metabolism were important metabolic pathways. This study reveals the histological, cytological and metabolic features of four-dose-gradient silica-induced pulmonary fibrosis mouse models.

AbstractWe comprised metabolites of gut microbiota (GM; endogenous species) and dietary plant-derived natural flavonoids (DPDNFs; exogenous species) were known as potent effectors against non-alcoholic fatty liver disease (NAFLD) via network pharmacology (NP). The crucial targets against NAFLD were identified via GM and DPDNFs. The protein interaction (PPI), bubble chart and networks of GM or natural products- metabolites-targets-key signalling (GNMTK) pathway were described via R Package. Furthermore, the molecular docking test (MDT) to verify the affinity was performed between metabolite(s) and target(s) on a key signalling pathway. On the networks of GNMTK, Enterococcus sp. 45, Escherichia sp.12, Escherichia sp.33 and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin and myricetin as key metabolites (or dietary flavonoids); AKT Serine/Threonine Kinase 1 (AKT1), CF Transmembrane conductance Regulator (CFTR) and PhosphoInositide-3-Kinase, Regulatory subunit 1 (PIK3R1) as key targets are promising components to treat NAFLD, by suppressing cyclic Adenosine MonoPhosphate (cAMP) signalling pathway. This study shows that components (microbiota, metabolites, targets and a key signalling pathway) and DPDNFs can exert combinatorial pharmacological effects against NAFLD. Overall, the integrated pharmacological approach sheds light on the relationships between GM and DPDNFs.

Published in Artificial Cells, Nanomedicine, and Biotechnology: An International Journal (Vol. 50, No. 1, 2022)

Published in Artificial Cells, Nanomedicine, and Biotechnology: An International Journal (Vol. 50, No. 1, 2022)

AbstractLow-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound. It can help improve bone fracture repair and soft tissue healing. Our previous study found that LIPUS treatment could halt the chronic kidney disease (CKD) progression in mice; unexpectedly, we observed the improvement of CKD-reduced muscle weights by LIPUS treatment. Here, we further tested the protective potential of LIPUS on CKD-associated muscle wasting/sarcopenia using the CKD mouse models. Mouse models of both unilateral renal ischemia/reperfusion injury (IRI) with nephrectomy and adenine administration were used to induce CKD. LIPUS with condition of 3 MHz, 100 mW/cm2, 20 min/day was applied to the kidney of CKD mice. LIPUS treatment significantly reversed the increased serum BUN/creatinine levels in CKD mice. LIPUS effectively prevented the decrease in grip strength, muscle weight (soleus, tibialis anterior, and gastrocnemius muscles), cross-section areas of muscle fibres, and muscular phosphorylated Akt protein expression by immunohistochemistry, and the increase in muscular atrogenes Atrogin1 and MuRF1 protein expression by immunohistochemistry in CKD mice. These results indicated that LIPUS could help improve weak muscle strength, muscle mass loss, muscle atrophy-related protein expression, and Akt inactivation. LIPUS application may be an alternative non-invasive therapeutic intervention on the management of CKD-associated muscle wasting.

Osteoporosis is a common disease among the ageing society. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) is the aetiology of osteoporosis. α-Lipoic acid (ALA) is an antioxidant in the body, which can eliminate excess ROS in the body and inhibits levels of oxidative stress in cells. Herein, we designed PEGylated hollow gold nanoparticles (HGNPs) loaded with ALA (mPEG@HGNPs-ALA) to remove ROS in the treatment of osteoporosis. First, mPEG@HGNPs with a particle size of ∼63 nm has been successfully synthesized. By comparing the drug loading of mPEG@HGNPs, it was concluded that the optimal mass ratio of mPEG@HGNPs (calculated by the amount of gold) to ALA was ∼1:2. ABTS antioxidant assay showed that free radical removal ability. In vitro results revealed that the preparation had good biocompatibility. At the gold concentration of 1-150 μg/mL, the cell viability of mPEG@HGNPs was more than 100%, which indicated that it could promote the proliferation of osteoblasts. What's more, mPEG@HGNPs-ALA could effectively remove the ROS caused by H2O2 injury and improve the cell viability. According to these results, it can be considered that mPEG@HGNPs-ALA has the potential to treat osteoporosis.

AbstractThis review concentrates on how artificial cells can contribute to helping patients with COVID-19. Artificial cells have led to mRNA vaccines with more improvements to come. Excessive cytokines in severe COVID-19 can damage organs leading to death. Artificial cell-based collodion macroporous activated charcoal adsorbent can effectively remove middle molecular weight range molecules in patients. A novel hemoperfusion device based on collodion membrane macroporous synthetic resin effectively removes cytokines and recovery in COVID-19 patients. This has been approved as an emergency treatment for COVID-19 in China, Europe, and Canada. A recent nanobiotherapeutic containing haemoglobin and up to six times the concentration of red blood cell enzymes: catalase, superoxide dismutase and carbonic anhydrase. In an animal study, this can effectively lower the damaging increase in free radicals and the removal of increased tissue pCO2. This can also help as blood substitute for the severe and critical problem of COVID-19 pandemic donor blood supply crisis.KEY MESSAGESCOVID-19 and its variants have resulted in major pandemics, severe sicknesses, and deaths around the world. COVID-19 and its variants has only started less than 3 years ago, and it is even more recently that we know more about its mechanisms, requirements, prevention, and treatment. This being the case, this is the first review on the present status and future perspectives of the use of the principle of artificial cells for COVID-19 related to vaccines, treatment, and critical donor blood supply shortage.

AbstractHuman papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo, ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo.The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

AbstractRecent years have seen the development of a variety of mammalian library approaches for display and secretion mode. Advantages include library approaches for engineering, preservation of precious immune repertoires and their repeated interrogation, as well as screening in final therapeutic format and host. Mammalian display approaches for antibody optimization exploit these advantages, necessitating the generation of large libraries but in turn enabling early screening for both manufacturability and target specificity. For suitable libraries, high antibody integration rates and resulting monoclonality need to be balanced – we present a solution for sufficient transmutability and acceptable monoclonality by applying an optimized ratio of coding to non-coding lentivirus. The recent advent of microfluidic-assisted hit discovery represents a perfect match to mammalian libraries in secretion mode, as the lower throughput fits well with the facile generation of libraries comprising a few million functional clones. In the presented work, Chinese Hamster Ovary cells were engineered to both express the target of interest and secrete antibodies in relevant formats, and specific clones were strongly enriched by high throughput screening for autocrine cellular binding. The powerful combination of mammalian secretion libraries and microfluidics-assisted hit discovery could reduce attrition rates and increase the probability to identify the best possible therapeutic antibody hits faster.

AbstractPurpose The present study was carried out to evaluate anti-inflammatory and antiangiogenic attributes of simvastatin and its nanofilms containing silver nanoparticles.Methods Silver nanoparticles and simvastatin-loaded nanocomposite (SNSN) films were formulated by using polymeric solution (pectin + sericin) through casting solution method. Different in vitro and in vivo anti-inflammatory assays were performed. In addition, chick chorioallantoic membrane assay (CAM) was also employed for angiogenesis activity.Results FTIR spectra of the film depicted the presence of intact simvastatin. Differential scanning calorimetry exhibited no endothermic expression in F9 film thermogram. The simvastatin release from all films exhibited a burst effect. Cotton-pellet induced granuloma model study showed that high dose of simvastatin and indomethacin produced comparable (p < 0.05) anti-inflammatory effect. Noteworthy, RT-PCR showed dose-dependent, anti-oedematous effect of simvastatin through downregulation of serum TNF-α and interleukin-1ß levels. While results of CAM assay exhibited remarkable anti-angiogenic potential of SNSN films showing dissolved blood vessels network macroscopically.Conclusion To reiterate, simvastatin and its SNSN films can add significant contribution to the field of biomedicines due to their promising anti-inflammatory and antiangiogenic properties, however, clinical studies are required to validate their commercial use.

AbstractThis study aimed to synthesize the silver nanoparticles (SNPs) and loaded chitosan nanoparticles (LCNPs) using Euphorbia prostata based on their anticandidal activity. Antioxidant capacity and the total phenolic and total flavonoid content of plant samples and synthesized nanoparticles (NPs) were also evaluated. SNPs and LCNPs were prepared, respectively using chemical reduction of silver salt solution and ionotropic gelation method. The anticandidal activity was assessed by broth micro-dilution method and the antioxidant activity was determined using free-radical scavenging assays. The synthesized NPs after the optimization process were found to be spherical with sizes ranging from 12 to 100 nm. Spectroscopic analysis of NPs showed the appearance of peaks in prescribed wavelength ranging between 402 and 493 nm. The synthesized NPs showed potent anticandidal activity compared to the free extract. The SNPs formulations NpEPM 7.5 and NpEPMR 7.5, showed significantly low MIC values ranging between 2 and 128 µg/mL. In the case of LCNPs, NpEPM (4:1) and NpEPME (4:1) also showed lower MIC values ranging from 32 to 256 µg/mL. The plant samples as well as NPs showed antioxidant potential. In addition, plant extracts and NPs possess the potent biological potential and can be further investigated through in vivo experiments.