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Herpes simplex virus type 1 (HSV-1) is a highly prevalent viral infection with limited medications. Thus, search for safe and effective alternative treatments is urgently needed. Peganum harmala L. ( P. harmala ) praised with antiviral potential may afford a decent option against HSV-1. This study creatively integrated network pharmacology and nanoscience to objectively disclose the efficacy mechanism of P. harmala bioactive compounds and augment the antiviral potential of P. harmala against HSV-1 via nanotechnology. Network pharmacology analysis revealed MAPK 1, SRC, EGFR and JAK1 as the top putative HSV-1 genes highly enriched in MAPK, PI3K-Akt, and JAK-STAT signalling pathways and primarily associated with the efficacy mechanism of P. harmala bioactive compounds against HSV-1. Complementarily, four P. harmala nano-formulations were established, monitored using different pharmaceutical scores, and assessed against HSV-1 using plaque reduction assay. Experimentally speaking, P. harmala -CS-ZnO NPs showed higher zeta (+ 40.8) with particle-size (73.06 nm), higher entrapment (81.7%) with loading-capacity (6.8%), sustained release reaching 50.5% after 24 h and demonstrated the most promising observation against HSV-1, with viral inhibition of 54.1% which is double the effect of crude extract alone with acceptable cytotoxicity (CC 50  = 271.4 µg/ml). This enhanced effect is possibly due to the synergistic antiviral properties of P. harmala bioactive compounds, chitosan, and zinc oxide nanoparticles. This complex between the ingredients chemically detected by FT-IR analysis also improved stability, cellular uptake, viral inhibition, and bioavailability. Our findings offer a solid basis for more extensive and rational clinical integration of P. harmala in the pharmaceutical industry to rectify human herpes viruses.

Tertiary lymphoid structures (TLSs) provide specialized niches for immune cells, resulting in improved prognoses for patients undergoing cancer immunotherapy. Shaping TLS‐like niches may improve anti‐cancer immunity and overcome the current limitations of immune cell‐based immunotherapy. Here, it is shown that stromal vascular fraction (SVF) from adipose tissues can enhance dendritic cell (DC)‐mediated T cell immunity by inducing ectopic T lymphocyte clusters. SVF cells expanded ex vivo have phenotypes and functions similar to those of fibroblastic reticular cells in a secondary lymphoid organ, and their properties can be modulated using three‐dimensional spheroid culture and coculture with DCs spiked with antigen‐loaded iron oxide–zinc oxide core‐shell nanoparticles. Thereby, the combination of SVF spheroids and mature DCs significantly augments T cell recruitment and retention at the injection site. This strategy elicits enhanced antigen‐specific immune response and anti‐tumoral immunity in mice, illustrating the potential for a novel immunotherapeutic design using SVF as a structural scaffold for TLS. Expanded stromal vascular fraction (SVF) cells show similar functional characteristics to lymph node stromal cells. Coculturing of SVF cells and dendritic cells (DCs) shows reciprocal interaction to support one another and enhance T cell responses. in vivo engraftment of SVF spheroids and antigen‐loaded DCs actively induces ectopic T cell lymphoid cluster and enhance both local and systemic antigen‐specific immune responses.

Zinc oxide (ZnO) nanoparticles and their networks have been developed for use in various applications such as gas sensors and semiconductors. In this study, their antibacterial activity against under dual ultraviolet (UV) irradiation for disinfection was investigated. ZnO nanoparticles were synthesized and immobilized onto silicon (Si) wafers by self-assembly. The physicochemical properties and antibacterial activity of ZnO nanoparticles and their networks were evaluated. Gene ontology was analyzed and toxicity levels were also monitored. Synthesized ZnO nanoparticles were spherical nanocrystals (<100 nm; Zn, 47%; O, 53%) that formed macro-mesoporous three-dimensional nanostructures on Si wafers in a concentration-dependent manner. ZnO nanoparticles and their networks on Si wafers had an excellent antibacterial activity against under dual UV irradiation (>3log CFU/mL). Specifically, arrayed ZnO nanoparticle networks showed superior activity compared with free synthesized ZnO nanoparticles. Oxidative stress-responsive proteins in were identified and categorized, which indicated antibacterial activity. Synthesized ZnO nanoparticles were less cytotoxic in HaCaT with an IC50 of 6.632 mg/mL, but phototoxic in Balb/c 3T3. The results suggested that ZnO nanoparticles and their networks can be promising photocatalytic antibiotics for use in next-generation disinfection systems. Their application could also be extended to industrial and clinical use as effective and safe photocatalytic antibiotics.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti-tumor agent for the treatment of gingival cancer.

SARS-CoV-2 has caused more than 596 million infections and 6 million fatalities globally. Looking for urgent medication for prevention, treatment, and rehabilitation is obligatory. Plant extracts and green synthesized nanoparticles have numerous biological activities, including antiviral activity. HPLC analysis of C. dirnum L. leaf extract showed that catechin, ferulic acid, chlorogenic acid, and syringic acid were the most major compounds, with concentrations of 1425.16, 1004.68, 207.46, and 158.95 µg/g, respectively. Zinc nanoparticles were biosynthesized using zinc acetate and C. dirnum extract. TEM analysis revealed that the particle size of ZnO-NPs varied between 3.406 and 4.857 nm. An XRD study showed the existence of hexagonal crystals of ZnO-NPs with an average size of 12.11 nm. Both ZnO-NPs (IC50 = 7.01 and CC50 = 145.77) and C. dirnum L. extract (IC50 = 61.15 and CC50 = 145.87 µg/mL) showed antiviral activity against HCOV-229E, but their combination (IC50 = 2.41 and CC50 = 179.23) showed higher activity than both. Molecular docking was used to investigate the affinity of some metabolites against the HCOV-229E main protease. Chlorogenic acid, solanidine, and catchin showed high affinity (−7.13, −6.95, and −6.52), compared to the ligand MDP (−5.66 Kcal/mol). Cestrum dinurum extract and ZnO-NPs combination should be subjected to further studies to be used as an antiviral drug.

Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in a variety of fields such as industrial, pharmaceutical, and household applications. Increasing evidence suggests that ZnO NPs could elicit unignorable harmful effect to the cardiovascular system, but the potential deleterious effects to human cardiomyocytes remain to be elucidated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been increasingly used as a promising in vitro model of cardiomyocyte in various fields such as drug cardiac safety evaluation. Herein, the present study was designed to elucidate the cardiac adverse effects of ZnO NPs and explore the possible underlying mechanism using hiPSC-CMs. ZnO NPs were characterized by transmission electron microscopy and dynamic light scattering. The cytotoxicity induced by ZnO NPs in hiPSC-CMs was evaluated by determination of cell viability and lactate dehydrogenase release. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by high-content analysis (HCA). Mitochondrial biogenesis was assayed by detection of mtDNA copy number and PGC-1α pathway. Moreover, microelectrode array techniques were used to investigate cardiac electrophysiological alterations. We demonstrated that ZnO NPs concentration- and time-dependently elicited cytotoxicity in hiPSC-CMs. The results from HCA revealed that ZnO NPs exposure at low-cytotoxic concentrations significantly promoted ROS generation and induced mitochondrial dysfunction. We further demonstrated that ZnO NPs could impair mitochondrial biogenesis and inhibit PGC-1α pathway. In addition, ZnO NPs at insignificantly cytotoxic concentrations were found to trigger cardiac electrophysiological alterations as evidenced by decreases of beat rate and spike amplitude. Our findings unveiled the potential harmful effects of ZnO NPs to human cardiomyocytes that involve mitochondrial biogenesis and the PGC-1α pathway that could affect cardiac electrophysiological function.

With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity.

To study the cytotoxic evaluation, antimicrobial and confocal analysis of zinc oxide nanoparticles (ZnO NPs) obtained from a novel plant product fennel ( Mill.) seed extract (FSE). ZnO NPs were analyzed using UV-Vis spectroscopy, XRD, FTIR, TEM and EDX techniques. The MTT cell cytotoxicity assay measured the proliferation and survival of MCF-7 cells treated at different concentrations of FSE-derived ZnO NPs. The antimicrobial activity towards pathogenic bacteria and yeast strains was investigated. The UV-Vis spectra showed two peaks at 438 nm and 446 nm, confirming nanoparticle formation. The SEM morphology results showed porous ranging from 23-51 nm. The antitumor activity value (IC ) was at 50 µg/mL and 100 µg/mL. Besides, morphological changes of MCF-7, cells treated at different concentrations of FSE of ZnO NPs were observed in cell cultures transfected with a transient pCMV6-XL4-GFP-expressing vector containing C-terminal domain GFP-tagged proteins, which resulted in an apoptotic effect. Antimicrobial IZ ranged up No Inhibition to 18.00 ± 0.4. The IZ revealed at the highest concentration was VRE and yeast sp. (18.00 ± 0.4. mm), followed by (17.00 ± 0.2 mm) and and the yeast (16 ± 0.4 mm). The IZ was equal to that caused by the nystatin to sp., which was significantly highest than ampicillin treatments of , and . The MIC value of the FSE-derived ZnO NPs tested against E.faecium and C.albicans was 6.00 µg/mL ( and ). It was 32.00 µg/mL ( and sp.), 64.00 µg/mL ( ), and 128 µg/mL ( ). As far as it is to our knowledge, this study established, for the first time, the biological activities of biosynthesized ZnO NPs from FSE and their synergistic therapeutic potential.

Aim: The aim of this study was to investigate the selected properties of zinc oxide- polymethyl methacrylate (ZnO-PMMA) nanocomposites that can influence the microorganism deposition on their surface. Materials and Methods: Non-commercial ZnO-NPs were prepared, characterized and used for the preparation of PMMA nanocomposite. Roughness, absorbability, contact angle and hardness of this new nanomaterial were evaluated. PMMA without ZnO-NPs served as control. Outcomes: Compared to unenriched PMMA, incorporation of ZnO-NPs to 7.5% for PMMA nanocomposite increases the hardness (by 5.92%) and the hydrophilicity. After modification of the material with zinc oxide nanoparticles the roughness parameter did not change. All tested materials showed absorption within the range of 1.82 to 2.03%, which meets the requirements of International Organization for Standardization (ISO) standards for denture base polymers. Conclusions: The results showed no significant deterioration in the properties of acrylic resin that could disqualify the nanocomposite for clinical use. Increased hydrophilicity and hardness with absorbability within the normal range can explain the reduced microorganism growth on the denture base, as has been proven in a previous study.

Metal oxide nanoparticles (NPs), such as ZnO, ZnFe 2 O 4 , and Fe 2 O 3 , are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe 2 O 4 , and Fe 2 O 3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC 50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe 2 O 4 , and Fe 2 O 3 ; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe 2 O 4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe 2 O 4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe 2 O 4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe 2 O 4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.