Photocatalytic Nanocomposite Based on Titanate Nanotubes Decorated with Plasmonic Nanoparticles for Enhanced Broad-Spectrum Antibacterial Activity.

Infections resulting from microorganisms pose an ongoing global public health challenge, necessitating the constant development of novel antimicrobial approaches. Utilizing photocatalytic materials to generate reactive oxygen species (ROS) presents an appealing strategy for combating microbial threats. In alignment with this perspective, sodium titanate nanotubes were prepared by scalable hydrothermal method using TiO2 and NaOH. Ag, Au, and Ag/Au-modified titanate nanotubes (TNTs) were prepared by a cost-effective and simple ion-exchange method. All samples were characterized by XRD, FT-IR, HRTEM, and DLS techniques. HRTEM images indicated that the tubular structure was preserved in all TNTs even after the replacement of Na+ with Ag+ and/or Au3+ ions. The antibacterial activity in dark and sunlight conditions was evaluated using different bacterial strains, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results showed that while a low bacterial count (∼log 5 cells per well) was used for inoculation, the TNTs exhibited no antibacterial activity against the three bacterial strains, regardless of whether they were tested under light or dark conditions. However, the plasmonic nanoparticle-decorated TNTs showed remarkable activity in the dark. Additionally, Ag/Au-TNTs demonstrated significantly higher activity in the dark compared with either Ag-TNTs or Au-TNTs alone. Notably, under dark conditions, the Au/Ag-TNTs achieved log reductions of up to 4.5 for P. aeruginosa, 5 for S. aureus, and 3.7 for E. coli. However, when exposed to sunlight, Au/Ag-TNTs resulted in a complete reduction (log reduction ∼9) for P. aeruginosa and E. coli. The combination of two plasmonic nanoparticles (Ag/Au) decorated on the surface of TNTs showed synergetic bactericidal activity under both dark and light conditions. Ag/Au-TNTs could be explored to design surfaces that are responsive to visible light and exhibit antimicrobial properties.

Nanoencapsulation of general anaesthetics.

General anaesthetics are routinely used to sedate patients during prolonged surgeries and administered via intravenous injection and/or inhalation. All anaesthetics have short half-lives, hence the need for their continuous administration. This causes several side effects such as pain, vomiting, nausea, bradycardia, and on rare occasions death post-administration. Several clinical trials studied the synergetic effect of a combination of anaesthetic drugs to reduce the drug load. Another solution is to encapsulate anaesthetics in nanoparticles to reduce their dose and side effects as well as achieve their sustained release manner. Different types of nanoparticles were developed as carriers of intravenous and intrathecal anaesthetics generating platforms which facilitate drug transport across the blood-brain barrier (BBB). Nanocarriers encapsulating common anaesthetic drugs such as propofol, etomidate, and ketamine were developed and characterized in terms of size, stability, onset and duration of loss of right reflex, and tolerance to pain in small animal models. The review discusses the types of nanocarriers used to reduce the side effects of the anaesthetic drugs while prolonging the sedation time. More rigorous studies are still required to evaluate the nanocarrier formulations regarding their ability to deliver anaesthetic drugs across the BBB, safety, and finally applicability in clinical settings.

Impact of HepG2 Cells Glutathione Depletion on Neutral Sphingomyelinases mRNA Levels and Activity.

Liver cancer is a prevalent form of cancer worldwide. While research has shown that increasing sphingomyelin (SM) hydrolysis by activating the cell surface membrane-associated neutral sphingomyelinase 2 (nSMase2) can control cell proliferation and apoptosis, the role of total glutathione depletion in inducing tumor cell apoptosis via nSMase2 activation is still under investigation. Conversely, glutathione-mediated inhibition of reactive oxygen species (ROS) accumulation is necessary for the enzymatic activity of nSMase1 and nSMase3, increased ceramide levels, and cell apoptosis. This study evaluated the effects of depleting total glutathione in HepG2 cells using buthionine sulfoximine (BSO). The study assessed nSMases RNA levels and activities, intracellular ceramide levels, and cell proliferation using RT-qPCR, Amplex red neutral sphingomyelinase fluorescence assay, and colorimetric assays, respectively. The results indicated a lack of nSMase2 mRNA expression in treated and untreated HepG2 cells. Depletion of total glutathione resulted in a significant increase in mRNA levels but a dramatic reduction in the enzymatic activity of nSMase1 and nSMase3, a rise in ROS levels, a decrease in intracellular levels of ceramide, and an increase in cell proliferation. These findings suggest that total glutathione depletion may exacerbate liver cancer (HCC) and not support using total glutathione-depleting agents in HCC management. It is important to note that these results are limited to HepG2 cells, and further studies are necessary to determine if these effects will also occur in other cell lines. Additional research is necessary to explore the role of total glutathione depletion in inducing tumor cell apoptosis.

Facile synthesis of zinc acetate/niacin MOFs for use in wound healing.

Niacin (NA) and zinc (Zn) were used to fabricate metal organic frameworks (Zn-NA MOFs), based on coordination chemistry via a simple, rapid technique conducted at room temperature. The identity of the prepared MOFs was confirmed by Fourier-transform infrared, x-ray diffraction, scanning electron microscopy, and transmission electron microscopy, which showed cubic shaped, crystalline, microporous MOFs with an average size of 150 nm. Release of the active ingredients from the MOFs was proved to be pH dependent in a slightly alkaline medium (pH 8.5) with a sustained release rate of its two ingredients, NA and Zn, which have wound healing activity. Zn-NA MOFs proved to be biocompatible in the tested concentrations range (5-100 mg ml-1), with no cytotoxic effect on WI-38 cell line. Zn-NA MOFs at 10 and 50 mg ml-1concentrations and their components, NA and Zn, exerted antibacterial effects againstStaphylococcus aureus, Escherichia coli, andPseudomonas aeruginosa. Wound healing effect of the Zn-NA MOFs (50 mg ml-1) was evaluated on full excisional rat wounds. Significant reduction of the wound area was observed after 9 d of treatment using the Zn-NA MOFs compared to the other treatment groups. Additionally, wounds were fully healed after 10 d of treatment with the Zn-NA MOFs with histological and immunohistochemical evidence of re-epithelization, collagen formation, and angiogenesis. Similar histological evidence was also observed in wounds treated with niacin only; however, with no significant wound closure rates. Nevertheless, the formation of new blood vessels, as confirmed by the vascular endothelial growth factor protein expression, was highest in the niacin group. Zn-NA MOFs synthesized using a facile, low-cost method are potentially capable of healing wounds rapidly and effectively.

Adult skin fibroblast state change in murine wound healing.

Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure.

Optical chemosensors for environmental monitoring of toxic metals related to Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia and progresses from mild memory loss to severe decline in thinking, behavioral and social skills, which dramatically impairs a person's ability to function independently. Genetics, some health disorders and lifestyle have all been connected to AD. Also, environmental factors are reported as contributors to this illness. The presence of heavy metals in air, water, food, soil and commercial products has increased tremendously. Accumulation of heavy metals in the body leads to serious malfunctioning of bodily organs, specifically the brain. For AD, a wide range of heavy metals have been reported to contribute to its onset and progression and the manifestation of its hallmarks. In this review, we focus on detection of highly toxic heavy metals such as mercury, cadmium, lead and arsenic in water. The presence of heavy metals in water is very troubling and regular monitoring is warranted. Optical chemosensors were designed and fabricated for determination of ultra-trace quantities of heavy metals in water. They have shown advantages when compared to other sensors, such as selectivity, low-detection limit, fast response time, and wide-range determination under optimal sensing conditions. Therefore, implementing optical chemosensors for monitoring levels of toxic metals in water represents an important contribution in fighting AD.

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation.

Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.

Multifunctional Hemostatic PVA/Chitosan Sponges Loaded with Hydroxyapatite and Ciprofloxacin.

The present study describes the development of multifunctional hemostatic sponges to control bleeding. Chitosan (Ch) and poly(vinyl alcohol) (PVA) were selected as the basic polymeric matrix [Ch/PVA] for sponges. Glycerol and citric acid were used as crosslinkers [Ch/PVA/G(Cl)] to enhance the mechanical properties of the developed sponges. Ciprofloxacin (AB) was added to the developed sponge to impart antibacterial activity. Hydroxyapatite (HA) was also added, which would make the sponge suitable for bone surgery. Among the developed sponges, the Ch/PVA/G(Cl)-HA-AB sponge demonstrated enhanced cell viability, mechanical properties, and strong antimicrobial effect against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, in addition to platelet aggregation activity. The addition of ciprofloxacin and hydroxyapatite promotes a unique synergistic effect of antimicrobial activity and hemostasis. Thus, the present study introduces Ch/PVA/G(Cl)-HA-AB, a multifunctional hemostatic sponge that would be suitable for bone surgical applications.

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion.

Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and ß2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

Facilitating SARS CoV-2 RNA-Dependent RNA polymerase (RdRp) drug discovery by the aid of HCV NS5B palm subdomain binders: In silico approaches and benchmarking.

Corona Virus 2019 Disease (COVID-19) is a rapidly emerging pandemic caused by a newly discovered beta coronavirus, called Sever Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2). SARS CoV-2 is an enveloped, single stranded RNA virus that depends on RNA-dependent RNA polymerase (RdRp) to replicate. Therefore, SARS CoV-2 RdRp is considered as a promising target to cease virus replication. SARS CoV-2 polymerase shows high structural similarity to Hepatitis C Virus-1b genotype (HCV-1b) polymerase. Arising from the high similarity between SARS CoV-2 RdRp and HCV NS5B, we utilized the reported small-molecule binders to the palm subdomain of HCV NS5B (genotype 1b) to generate a high-quality DEKOIS 2.0 benchmark set and conducted a benchmarking analysis against HCV NS5B. The three highly cited and publicly available docking tools AutoDock Vina, FRED and PLANTS were benchmarked. Based on the benchmarking results and analysis via pROC-Chemotype plot, PLANTS showed the best screening performance and can recognize potent binders at the early enrichment. Accordingly, we used PLANTS in a prospective virtual screening to repurpose both the FDA-approved drugs (DrugBank) and the HCV-NS5B palm subdomain binders (BindingDB) for SARS CoV-2 RdRp palm subdomain. Further assessment by molecular dynamics simulations for 50 ns recommended diosmin (from DrugBank) and compound 3 (from BindingDB) to be the best potential binders to SARS CoV-2 RdRp palm subdomain. The best predicted compounds are recommended to be biologically investigated against COVID-19. In conclusion, this work provides in-silico analysis to propose possible SARS CoV-2 RdRp palm subdomain binders recommended as a remedy for COVID-19. Up-to-our knowledge, this study is the first to propose binders at the palm subdomain of SARS CoV2 RdRp. Furthermore, this study delivers an example of how to make use of a high quality custom-made DEKOIS 2.0 benchmark set as a procedure to elevate the virtual screening success rate against a vital target of the rapidly emerging pandemic.

Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages.

Doxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

Intranasal lipid nanocapsules for systemic delivery of nimodipine into the brain: In vitro optimization and in vivo pharmacokinetic study.

Nimodipine (NM) is FDA-approved drug for treating subarachnoid haemorrhage induced vasospasm. Intravenous (IV) administration, the most common route of NM, causes several side effects such as hypotension, bradycardia, arrhythmias and inflammation at site of administration. The aim of this study was to investigate the capability of intranasal (IN) lipid nanocapsules (LNCs) for effective delivery of NM into the brain. NM LNCs were prepared by solvent free phase inversion temperature technique using D-Optimal mixture design studying the effects of three formulation variables on the properties of the prepared LNCs. The prepared particles were evaluated for particle size, drug payload, PDI, Zeta potential and in-vitro drug release. The optimized NM loaded LNC showed particle size of 35.94 ± 0.14 nm and PDI of 0.146 ± 0.045. The in-vivo pharmacokinetic behaviour of IN NM loaded LNC in blood and brain was compared with NM-solution after IV administration in rats. Results show that IN NM loaded LNC was capable to deliver the same amount of NM at brain tissue with lower drug levels in blood compared with IV administration of the NM solution which is greatly beneficial to minimize the cardiovascular side effects of NM. Contrary to most IN nanocarriers, systemic pathway rather than olfactory pathway plays the major role in brain delivery following IN administration of LNCs. The appropriate brain delivery with lower blood levels and slow elimination propose that intranasal LNCs could provide effective systemic delivery of NM into brain with lower frequency of administration and minimal side effects.

Turmeric/oregano formulations for treatment of diabetic ulcer wounds.

Diabetic wound infections and pressure ulcers pose a significant challenge to healthcare providers worldwide. The current study provides new and innovative wound care products that reduce inflammation, clear infection, and improve healing in an animal model of pressure ulcers in diabetic rats. Ointment, hydrogel, and nanofiber dressings were synthesized using 5% turmeric, 1% oregano, and 1% chitosan nanoparticles and tested for antibacterial and cytotoxicity in vitro, and wound healing effects in vivo. Turmeric ethanolic extract showed high antioxidant activity compared to Oregano, Chitosan Nanoparticles, and Alginate silver (p-value < 0.0001). The ointment and hydrogel formulation (5% Turmeric, 1% Oregano, and 1% chitosan) showed lower cytotoxicity compared to the commercial Alginate silver dressing. Ointment, hydrogel formulations, and commercial Alginate silver, showed significant antibacterial activity with 100% efficacy on both Staphylococcus aureus and Escherichia coli (p-value < 0.0001), compared to nanofibers which showed 50% reduction in bacterial growth (p-value < 0.0001). The new formulations were tested in a rat model of pressure ulcers. Ointment and nanofibers achieved complete wound healing by day 15 compared to the hydrogel and commercial Alginate silver dressing, which showed higher infection, and the wound remained partially open by day 21. In conclusion, Turmeric, Oregano extracts, and chitosan nanoparticles can be used for effective wound dressings in both diabetic and non-diabetic wounds. At relatively low concentrations, this combination provides a promising new wound treatment formulation that is antibacterial, anti-inflammatory, and antioxidant.

Detection of Acinetobacter baumannii in fresh produce using modified magnetic nanoparticles and PCR.

Foodborne pathogens represent a major public health concern. In this respect, Acinetobacter baumannii is emerging as multi-drug resistant food pathogen. Screening of A. baumannii in food is a lengthy process. The aim of this study is to develop a fast and efficient protocol for detecting A. baumannii as well as other potential pathogens in fresh food. A. baumannii was collected from strawberry samples (n = 93) and were identified by DNA sequencing and polymerase chain reaction (PCR; recA). Hydrophobic magnetic nanoparticles (OA-MNP) were synthesized and tested for capturing A. baumannii and other bacteria from broth medium. Their ability to immobilize bacteria was assessed and the accuracy of PCR performed on immobilized bacteria was compared against control. A. baumannii (n = 14) was isolated form fresh produce as confirmed by sequencing and PCR. OA-MNPs were able to capture A. baumannii as well as other bacteria from broth medium. Intact DNA was extracted from immobilized bacteria and was successfully recruited for subsequent PCR. In conclusion, OA-MNP can be used for immobilizing food pathogens from broth medium. PCR can be performed using DNA extracted from immobilized bacteria for identification. The proposed analysis procedure may shorten the time required for detection of bacterial contamination in food.

MicroRNA-208a: a Good Diagnostic Marker and a Predictor of no-Reflow in STEMI Patients Undergoing Primary Percutaneuos Coronary Intervention.

MicroRNA-208a is a cardiac specific oligo-nucleotide. We aimed at investigating the ability of microRNA-208a to diagnose myocardial infarction and predict the outcome of primary percutaneuos coronary angiography (PCI). Patients (n = 75) presented by chest pain were recruited into two groups. Group 1 (n = 40) had ST elevation myocardial infarction (STEMI) and underwent primary PCI: 21 patients had sufficient reperfusion and 19 had no-reflow. Group 2 (n = 35) had negative cardiac troponins (cTns). Plasma microRNA-208a expression was assessed using quantitative polymerase chain reaction and patients were followed for occurrence of in-hospital major adverse cardiac events (MACE). MicroRNA-208a could diagnose of MI (AUC of 0.926). After primary PCI, it was superior to cTnT in prediction of no-reflow (AUC difference of 0.231, P = 0.0233) and MACE (AUC difference of 0.367, P = 0.0053). Accordingly, circulating levels of miR-208a can be used as a diagnostic marker of MI and a predictor of no-reflow and in-hospital MACE. Graphical abstract Receiver operating curve analysis of no-reflow prediction of miRNA208a, CK-MB and hs-Troponin T. MicroRNA-208a shows significantly higher prediction of no-reflow as compared to routine cardiac biomarkers.

Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?

Human lungs single-cell RNA sequencing data from healthy donors (elderly and young; GEO accession no. GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Colocalization of angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 enables severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) to enter the cells. Expression levels of these genes in the alveolar type II cells of elderly and young patients were comparable and, therefore, do not seem to be responsible for worse outcomes observed in coronavirus disease 2019 (COVID-19) affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. Superoxide dismutase 3 (SOD3) was identified as the top-ranked gene that was most downregulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included activating transcription factor 4 (ATF4) and metallothionein 2A (M2TA). ATF4 is an endoplasmic reticulum stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway Analysis™, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this study propose the hypotheses that lung-specific delivery of SOD3/ATF4-related antioxidants will work in synergy with promising antiviral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.

Synthesis of magnetic iron oxide nanoparticles using pulp and seed aqueous extract of Citrullus colocynth and evaluation of their antimicrobial activity.

OBJECTIVES: Citrullus colocynth (CTC) is a wild medicinal plant with proven antimicrobial activity. The aim of this study is to investigate the use of its aqueous extract in producing magnetic iron oxide nanoparticles (MNPs) with improved antimicrobial activity. The cold and hot aqueous extract of seed and pulp parts of CTC, respectively, were used to produce MNPs. The particles were characterized by transmission electron microscope, energy dispersion x-ray, FTIR and their surface charge were measured. The antimicrobial activity of the produced particles was assessed against two Gram positive (Bacillus subtillis and Staphylococcus aureus) and two Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacteria and well as against Candida albicans. RESULTS: MNPs synthesized using cold seed extract (S-MNP) and pulp extract (P-MNP) were spherical in shape. The size distribution was more uniform in the S-MNP (6-15 nm) compared to the P-MNP (12-45 nm). Both particles showed comparable anti-microbial potential against the tested microorganisms. At a concentration range of 0.48-1000 µg/mL, S-MNP inhibited bacterial growth by 16.0-99.0% and 10.0-91.0%; while P-MNP inhibition was 11.0-100.0% and 11.0-99.0% for Gram positive and negative bacteria; respectively. Candida albicans was the least affected microorganism with maximum inhibition of 63-88% after treatment with S-MNP and P-MNP (1 mg/mL), respectively. CONCLUSIONS: The aqueous extract of CTC can be used for synthesis of MNPs with antimicrobial activity. The described procedures are simple and can be modified for large scale green synthesis of MNPs.

Nanogold Assay Improves Accuracy of Conventional TB Diagnostics.

PURPOSE: TB nanodiagnostics have witnessed considerable development. However, most of the published reports did not proceed beyond proof-of-concept. Our objectives are to evaluate the diagnostic accuracy of a novel nanogold assay in detecting patients with active pulmonary TB based on results of BACTEC MGIT (reference test), and to compare its clinical performance to combined use of sputum smear microscopy (SSM) with chest X-ray (CXR). METHODS: This is a case-control study that involved 20 active TB patients; 20 non-TB chest patients with a previous history of TB infection; 20 non-TB chest patients without a previous history of TB infection. RESULTS: Sensitivity and specificity of TB nanogold assay were 95% and 100%, respectively, with diagnostic odds ratio (DOR) of 1053.0. ROC curve analysis yielded an area under curve (AUC) of 0.975. TB nanogold assay generated higher performance than combined use of SSM with CXR. The DOR and AUC differences were 996.0 and 0.125, respectively. CONCLUSIONS: Our study shows that TB nanogold assay is accurate, rapid, and holds the potential for use as an add-on initial test to improve accuracy of SSM and CXR in detecting patients of active pulmonary TB in developing countries. Future studies should involve larger sample size for further assessment of test accuracy.

Nuclear and cytoplasmic delivery of lactoferrin in glioma using chitosan nanoparticles: Cellular location dependent-action of lactoferrin.

Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein.